Larval infestation of chronic ischaemic leg ulcer

Description

Several cases of obligatory wound myiasis have been reported in the medical literature.1–3 For a long time, such infestation was perceived as a complication of poor quality wound care in patients with chronic ulcers. There are only three cases of wound myiasis reported in the literature. Demirel et al reported on a 68-year-old male patient with larvae infestations of diabetic wound that were discovered during surgical debridement.3 Another two cases of traumatic larval infestation associated with Bowen carcinoma and with chronic leg ulcer were reported.3 Up to date, there is no report of chronic ulcer with massive larvae infestation as in this patient.

Figure 1 with video capture (video 1) demonstrates a massive larvae infestation of severe chronic ischaemic ulcer in a 60-year-old homeless male patient with HIV, who presented with unilateral leg pain without systemic or...

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Bilateral haemorrhagic basal ganglia infarction associated with early-onset group B streptococcus meningitis

A 2-day-old infant presented with poor feeding and grunting. Investigations revealed a raised C reactive protein of 164. Full septic screen was done, which subsequently confirmed a diagnosis of group B streptococcus meningitis. Baby was apyrexial and haemodynamically stable. There were no obvious neurological manifestations, and a routine cranial ultrasound scan was done, which revealed echogenic changes in the basal ganglia and thalami. MRI brain showed extensive haemorrhagic infarction within the lentiform and caudate nuclei with involvement of both posterior limbs of the internal capsule. This was followed by triventricular hydrocephalus needing shunt procedure. The clinical course was complicated by infantile spasms, which were treated with vigabatrin and steroids and subsequent global developmental delay and cerebral palsy.

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Hepatic amyloidosis: a cause of rapidly progressive jaundice

Description

An 83-year-old man presented with an acute history of weight loss and jaundice. He had a history of type 2 diabetes mellitus and hypertension. He consumed 30 units of alcohol per week.

The patient was cachectic and jaundiced with non-tender hepatomegaly and no evidence of chronic liver disease. There was evidence of hypoalbuminaemia (albumin 25 g/L, reference 34–51 g/L), hyperbilirubinaemia (bilirubin 188 μmol/L, reference <22 μmol/L) and a raised alkaline phosphatase (629 IU/L, reference 35–105 IU/L). Full blood count, coagulation tests and the remaining liver function tests were normal. An estimated Glomerular filtration rate (eGFR) was 71 mL/min/1.73 m². Autoantibodies and immunoglobulins were normal. Hepatitis viral serology was negative. Serum light chain measurements revealed kappa chain concentration of 13.3 (reference 3.3–19.4 mg/L) and lambda chain concentration of 28.5 (reference 5.7–26.6 mg/L) with a ratio of 0.47 (reference 0.26–1.75). A CT abdomen revealed hepatomegaly and ascites. He subsequently had a liver biopsy (figures 1–3

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Extraocular muscle cysticercosis: never skip steroids

DescriptionCase description

A 16-year-old girl presented with a 2-month history of recurrent (three episodes) right upper eyelid drooping and oedema (figure 1A). Examination showed fullness in the right upper eyelid along with elevation deficit. Visual acuity was 20/20 in each eye, and anterior and posterior segments were essentially within normal limits in both the eyes. To explain the cause, ultrasonography of the orbit for extraocular muscles revealed a large cyst in the superior rectus muscle along with a central hyperechoic spot corresponding to the scolex (figure 1B). Non-contrast CT of the orbit and brain revealed inflammatory thickening of the superior rectus muscle with the central cystic area harbouring the scolex without any intracranial foci (figure 1C). Based on the history and imaging findings a diagnosis of myocysticercosis was confirmed and the patient was started on tablet prednisolone 1mg/kg body weight from day 1 and tablet albendazole 15 mg/kg from day 3. The patient...

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Coats disease with exudative retinal detachment simulating cysticercus cyst: misleading ultrasonography!

Description

A 5-year-old boy was brought to our clinic when parents noticed white reflex and divergent squint in the left eye. Snellen visual acuity was 20/20 in the right eye and inaccurate projection of rays in the left eye along with a 30 prism dioptre divergent squint in the latter. Anterior segment was within normal limits in both eyes on slit lamp evaluation. As the child was uncooperative for detailed fundus examination, we performed an ocular ultrasonography. Ocular ultrasonography of the left eye showed an intraocular cystic mass with a localised hyperechoic area adjacent to cyst wall which is typical of a cysticercus cyst with scolex (figure 1). On Optomap ultra-wide-field fundus photography (Optos, Scotland, UK) we found that the cystic mass on ultrasonography was actually a localised exudative retinal detachment and the scolex-like area of hyperechogenicity was a large confluent exudate collection in the subretinal...

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Brain abscess in a patient with chronic sinusitis

Description

A middle-aged patient with a previous history of chronic sinusitis and arterial hypertension was admitted because of altered mental status. Two days earlier, symptoms such as fever, chills, nasal obstruction and headache slowly developed. On examination, the patient was febrile and with stiff neck. The remainder of the physical examination was normal. CT scan (figure 1A,B) and T1-MRI (figure 2A–C) were both performed; besides signs of sinusitis, a 2 cm right periatrial expansive lesion surrounded by vasogenic oedema was found being compatible with brain abscess. A thorough investigation was done to exclude infectious endocarditis, including echocardiography and blood cultures which were all negative. Viral serologies, including HIV, were negative. Based on the brain lesion characteristics (size and peculiar location), a conservative approach with broad-spectrum antibiotics (ceftriaxone, metronidazole and vancomycin) was initially suggested by Neurosurgery. However, 20 days after, the patient presented with neurological deterioration....

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Acute-on-chronic mesenteric ischaemia by early and diffuse atherosclerosis in a young adult patient

Description

A 48-year-old Caucasian man with gypsy ethnicity had smoking habits (35 pack-years) and previous alcohol consumption (10 g/day; abstinent for 3 years). There was no relevant personal/family cardiovascular disease, history of illicit drug abuse, non-steroidal anti-inflammatory drug use or other previous/current medications. He had a 3-year history of chronic diarrhoea (3–4 bowel movements/day), abdominal pain and weight loss (25.9% of usual weight; body mass index=13.7 kg/m²). In the last month, an exacerbation of abdominal pain occurred with excruciating postprandial episodes requiring opioid analgesia. Laboratory analysis showed leucocytosis (34.8; N: 4–11x10⁹/L), neutrophilia (90.6%), normocytic/normochromic anaemia (haemoglobin: 8.0; N: 13–17 g/dL), high Erythrocyte sedimentation rate (ESR) (54; N<20 mm/hour), faecal calprotectin (4890; n<50 mg/kg) and C-reactive protein (CRP) (10.7; N<0.5 mg/dL). Oesophagogastroduodenoscopy and ileocolonoscopy with biopsies showed multiple Helicobacter pylori-negative gastroduodenal ulcers (figure 1A,B) and non-specific mild ulceration of the terminal ileum and proximal colon, without granulomas. CT enterography showed distended small bowel loops without...

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Birt-Hogg-Dube syndrome: spontaneous pneumothorax as a first symptom

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary autosomal dominant condition characterised by benign cutaneous lesions, lung cysts, increased risk of spontaneous pneumothorax and renal cancer. It shows great heterogenous presentation within and between affected families. We report a case of a Danish female patient with recurrent pneumothoraces as the first symptom of BHDS. Over the years, she developed skin changes, and a family history of skin changes, pneumothoraces and renal cancer was discovered. BHDS was suspected, a genetic analysis was performed and a pathogenic variation c.1285delC in FLCN gene was detected in the patient. As we stated the diagnosis BHDS, we discovered several undiagnosed family members all of them now entering a lifelong follow-up programme with abdominal imaging because of the increased risk of developing renal cancer. BHDS should be known to oncologists, dermatologists and pulmonologists as the patients most often present to these medical disciplines.

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Iatrogenic foreign body in an adult with presbyacusis

Description

Foreign bodies in the external auditory meatus are a common presentation to Otolaryngology both to clinic and as an emergency.1 Most objects referred to Otolaryngology are round and hard such as beads and are more difficult to remove.1While many patients are aware of what might be in their ear, some do not. The causative event can be missed, and the symptoms can be non-specific.2 They may present with a foreign body sensation, a feeling of fullness in the ear, otalgia and recurrent otitis externa. Many of these symptoms can be applied to a presentation of impacted cerumen.

These images refer to a 67-year-old man who presented to Otolaryngology having been referred by his General Practitioner. On presentation to the clinic, he had persistent otalgia in the left ear and reduced hearing for the past 3 months. He also described a feeling of fullness...

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Superficial mycosis of the foot caused by Cladophialophora boppii

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Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry

Summary

Background

The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively.

Aims

To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry

Methods

Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer.

Results

The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61–0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64–0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I–III and IV, and ≥ 47 between IV and V–VI.

Conclusions

Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

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Dermoscopic characterization of cutaneous lymphomas: a pilot survey

Abstract

Background

While substantial dermoscopic analysis of melanocytic lesions has been performed, dermoscopic characterization of cutaneous lymphoid proliferations has been limited. Cutaneous lymphoma, particularly early mycosis fungoides (MF) and its variants, is often challenging to clinically and pathologically distinguish from inflammatory processes of the skin. This study aimed to survey the dermoscopic findings of cutaneous lymphomas and to discern whether any patterns might potentially serve as specific signatures.

Methods

Fifteen patients with an established diagnosis of cutaneous lymphoma were prospectively recruited and seen in the university multidisciplinary cutaneous lymphoma program with MF, an MF- variant, CD30-positive lymphoproliferative disorder, or cutaneous B-cell lymphomas and were included in our study. Dermoscopic findings, histologic features, clinical characteristics, and demographic data were analyzed.

Results

Patch stage MF was characterized by interconnected white structureless patches encircling small fine linear vessels, yielding an overall trabeculated to fenestrated pattern under dermoscopy. Corresponding histopathologic findings for these patterns included epidermotropism, atypical pleomorphic cells, and lichenoid infiltrates. Folliculotropic mycosis fungoides (FMF) was characterized by folliculocentric erosions surrounded by dotted and fine linear vessels, loss of terminal follicles, comedo-like openings, and interconnected regular-appearing structureless patches. Corresponding histopathologic findings in these FMF cases were typical of FMF. Notably, these changes were not appreciated in lymphomatoid papulosis. Primary cutaneous follicle center B cell lymphoma showed crystalline structures and vascular pseudopods.

Conclusions

Cutaneous lymphomas appear to demonstrate characteristic dermoscopic patterns, reflective of the specific lymphoma type and its corresponding histopathology, which have not been seen in inflammatory skin conditions, such as psoriasis and eczematous dermatitis.

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The early repigmentation pattern of vitiligo is related to the source of melanocytes and by the choice of therapy: a retrospective cohort study

Abstract

Background

Patients with vitiligo present with different repigmentation patterns in the early recovery stage.

Objectives

To analyze the relationships between early repigmentation patterns in vitiliginous patches, their clinical characteristics, and therapeutic choices.

Methods

Patients with vitiligo seen in the Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University from 2010 to 2015, were included, and their clinical records, especially photographs and medical treatments, were reviewed.

Results

One hundred and sixteen patients were included in this study, and 326 lesions with different degrees of depigmentation, locations, stages, distributions, therapies, and repigmentation patterns were included and analyzed. Perifollicular repigmentation occurred more frequently in lesions with complete depigmentation (P = 0.005), in non-sun exposed areas (P < 0.001), a stable stage (P = 0.008), and lesions treated with narrow band ultraviolet B (NB-UVB) (P < 0.001, despite lesion distributions). Marginal repigmentation is more frequent in lesions with complete depigmentation (P = 0.016), lesions treated without NB-UVB (P = 0.002), and facial lesions treated with topical vitamin D analogs (TVDAs) monotherapy (P = 0.022). Diffuse repigmentation is the predominant pattern in lesions with incomplete depigmentation (P < 0.001), in sun-exposed areas (P < 0.001), progressive stage (P = 0.044), and truncal lesions treated with TVDAs (P < 0.001).

Conclusions

The different repigmentation patterns of vitiligo lesions depend on the different source and status of melanocytes and their abilities to produce melanin on the choice of therapy.

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Interested in global health? Here is where to start: a checklist for United States dermatology residents

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Isolation and molecular characterization of zoonotic Buffalopox virus from skin lesions of humans in India

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Efficacy and safety of noncultured melanocyte-keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence

Abstract

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte-keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001–2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in-depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.

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Hypopigmented mycosis fungoides: a 20-case retrospective series

Abstract

Background

Hypopigmented mycosis fungoides (hMF) is a rare subtype of mycosis fungoides. The aim of this study was to identify the clinical–epidemiological profile of our patient group and also to provide additional information about treatment responses and prognosis.

Methods

This is a cross-sectional retrospective observational study, with exploratory analysis. The outcome variables were disease progression and related death.

Results

Twenty patients with hMF were selected from a group of 102 patients diagnosed with MF. There was no gender difference (10 females and 10 males). Mean age at diagnosis was 43.85 years, and most patients had mixed or black skin color. The mean time between the onset of the lesions and the diagnosis was 66.75 months. Patients were equally distributed in stages IA (50%) and IB (50%). Photochemotherapy (psoralen and ultraviolet A) was the predominant therapeutic modality. The mean follow-up time was 7.25 years. In 10%, disease progression was observed. Death related to the disease occurred in one patient.

Conclusions

The clinical and epidemiological profile of patients with hypopigmented MF found in our sample is in agreement with what is described in the literature, with the exception of the age at diagnosis, higher than expected. Diagnostic delay time, despite long, is also consistent with the medical literature; however, in this sample, we had two cases of disease progression, with death of one patient, despite the treatment, which is extremely important since hypopigmented MF is usually associated with good prognosis.

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The usefulness of nail plate and intraoperative dermoscopy in subungual glomus tumor

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Eruptive keratoacanthomas secondary to nivolumab immunotherapy

http://ift.tt/2CP1wNu

Idiopathic chilblains in myelomonocytic leukemia: not a simple association

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Localized nodular pemphigoid

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Evaluation of ICAM-1 expression and vascular changes in the skin of patients with plaque, pustular, and erythrodermic psoriasis

Abstract

Background

Psoriasis is a chronic inflammatory disease. Pustular, erythrodermic, and extensive plaque psoriasis are responsible for systemic complications. Systemic capillary leak syndrome is the complication with greater progression to death and occurs due to vascular changes.

Purpose

The aim of this study was to evaluate vascular changes through the expression of CD34 and ICAM-1 in plaque, pustular, and erythrodermic psoriasis.

Methods

The sample consisted of seven patients with erythrodermic psoriasis, 24 with moderate-severe plaque psoriasis, 14 with mild plaque psoriasis and 13 with pustular psoriasis. Patients were submitted to physical examination and skin biopsy for histopathological examination and immunohistochemical analysis with anti-CD34 and anti-ICAM-1 antibodies. Subsequently, tissue fragments were organized by groups using the Tissue Macroarray (TMA) technique to perform immunohistochemistry.

Results

In 58 patients, analysis of vessels using anti-CD34 demonstrated vascular immunostaining in superficial dermis and between dermal papillae. There were more blood vessels in erythrodermic psoriasis, followed by plaque psoriasis. In erythrodermic psoriasis, there were small and few tortuous blood vessels with great dilatation, while plaque psoriasis presented larger vessels that were less dilated and more tortuous. There was an intense and localized expression of ICAM-1 in endothelial and lymphocytic cells in all groups, with significant differences.

Conclusions

Vascular alterations are important in psoriasis, with an increase in the number of blood vessels and ICAM-1 overexpression, especially in erythrodermic form. Therefore, vascular changes and the expression of intercellular adhesion molecules could help to diagnose the erythrodermic form of psoriasis.

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Dermoscopy of childhood flexural comedones: description of 4 cases

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Remission of refractory metastatic Crohn's disease achieved with dapsone

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Clinico-etiologic profile of hand dermatitis and patch response of patients at a tertiary hospital in Lagos, Nigeria: results of a prospective observational study

Abstract

Background

Hand dermatitis is an acute or chronic inflammation of the skin of the hands from a multifactorial cause which may be endogenous, exogenous, or a combination of both. With a wide range in severity and recurrent periods of flares, it has significant impact on the quality of life of its sufferers. A history of atopy predisposes patients to hand dermatitis, but contact dermatitis, either allergic or irritant, is the more commonly implicated factor in the etiology of hand dermatitis. Patch testing is an important tool in identifying the allergen responsible for allergic hand dermatitis, and this knowledge will contribute to improved management.

Aim and Objectives

This study was undertaken to evaluate the clinical and etiologic profile and review the patch responses of patients who presented with hand dermatitis at a foremost tertiary skin clinic in the most populous state of the most populous country in Africa.

Methods

A prospective, observational study in which consecutive walk-in patients who fulfilled the inclusion criteria were enrolled. Ethical clearance was obtained. Study tools included self-administered questionnaires, physical examination, and patch tests (European Hermal series), amongst others. The patch tests were carried out. Results were documented, and treatment was individualized based on clinical and investigation findings. The results were collated and analyzed with SPSS^® 17.0 edition (SPSS II).

Results

Hand dermatitis was seen in 177 (13.3%) patients who presented during the study period. The mean age was 34.6 + 17.4 years. Almost two-thirds of patients (119; 67.2%) had chronic hand dermatitis, while 53 (32.8%) presented acutely. Patch responses were positive in 65 (36.7%) patients with paraphenylenediamine identified as the most frequent cause. Respondents had at least one (+) response to 20 of the 28 allergens, while there was no response to eight of the allergens in the European series.

Conclusion

The study reveals that hand dermatitis is present in a younger age group and a variety of subtypes coexist. Locally sourced allergens are needed to improve the yield of patch responses.

http://ift.tt/2CP1tRO

Nail changes in alopecia areata: an update and review

Abstract

Nail changes are a common feature of alopecia areata (AA) and are a significant source of cosmetic disfigurement and functional impairment. This review provides an update of the prevalence, clinical and histopathological features, pathogenesis, differential diagnosis, clinical course, prognosis, and management of nail changes in patients with AA. Searches for peer-reviewed journal articles were conducted using the PubMed/MEDLINE database with the search terms "nail changes alopecia areata," "alopecia areata nails," and specific searches on "trachyonychia alopecia areata" and "pitting alopecia areata." Other sources of articles included the reference lists of retrieved articles. Nail changes are a common feature of AA, with an average prevalence of 30%, and can cause significant disfigurement and loss of function. Pitting and trachyonychia were by far the most common manifestations of AA, with an average prevalence of 20 and 8%, respectively. Red spotted lunulae, onycholysis, and punctate leukonychia were other reported findings. Other etiologies, such as onychomycosis or lichen planus, may coexist with or confound the diagnosis. There is limited published data on the clinical manifestations of AA-associated nail changes and therapeutic options. Larger controlled trials are necessary to guide treatment decisions.

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Comparative evaluation of skin moisture after topical application of 10% and 30% lactobionic acid

Summary

Background

Dry skin is characterized by symptoms such as itching, redness, excessive exfoliation. These symptoms cause discomfort and contribute to secondary bacterial infections. Dry skin treatments are based on topical applications of various formulations. Among many of them are polyhydroxy acids, which recently gained more attention.

Aims

The aim of this study was a comparative assessment of hydration level (corneometric) after application of lactobionic acid (LA) in the form of peel at concentrations of 10% and 30%.

Material and Methods

The study involved 10 Caucasian individuals aged 26-73 years. Eight treatments were performed at weekly intervals. The peels were applied using the "Split face" method—on the left side of the face 10% LA, and the right side 30% LA which consisted of specified concentration of LA, deionized water, xanthan gum, ethoxydiglycol. The test subjects received a 5% LA cream for overnight use. The cream consisted of deionized water, LA, isopropyl palmitate, ascorbyl palmitate, methylparaben. The products for this study were provided by Grehen Ltd. Celestynów, Poland. Prior to each procedure, the skin hydration level was measured using Corneometer CM 825 from Courage + Khazaka electronic GmbH.

Results

There was a statistically significant improvement in hydration level after 8 treatments for all measuring points and both concentrations. The difference of the skin hydration level between 10% LA and 30% LA could not be determined.

Conclusions

Lactobionic acid is a highly moisturizing agent. There was no significant difference in moisturizing effect between 10% LA concentration and 30% LA concentration.

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Post-herpes zoster sarcoidosis as a recurrence

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Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Maxime D. Slooter, Henricus J.M. Handgraaf, Martin C. Boonstra, Lily-Ann van der Velden, Shadhvi S. Bhairosingh, Ivo Que, Lorraine M. de Haan, Stijn Keereweer, Pieter B.A.A. van Driel, Alan Chan, Hisataka Kobayashi, Alexander L. Vahrmeijer, Clemens W.G.M. Löwik
ObjectivesTumour-positive resection margins are a major problem during oral cancer surgery. gGlu-HMRG is a tracer that becomes fluorescent upon activation by gamma-glutamyltranspeptidase (GGT). This study aims to investigate the combination of gGlu-HMRG and a clinical fluorescence imaging system for the detection of tumour-positive resection margins.Materials and methodsThe preclinical Maestro and clinical Artemis imaging systems were compared in vitro and ex vivo with cultured human head and neck cancer cells (OSC19, GGT-positive; and FaDu, GGT negative) and tumour-bearing nude mice. Subsequently, frozen sections of normal and oral cancer tissues were ex vivo sprayed with gGlu-HMRG to determine the sensitivity and specificity. Finally, resection margins of patients with suspected oral cancer were ex vivo sprayed with gGlu-HMRG to detect tumour-positive resection margins.ResultsBoth systems could be used to detect gGlu-HMRG activation in vitro and ex vivo in GGT positive cancer cells. Sensitivity and specificity of gGlu-HMRG and the Artemis on frozen tissue samples was 80% and 87%, respectively. Seven patients undergoing surgery for suspected oral cancer were included. In three patients fluorescence was observed at the resection margin. Those margins were either tumour-positive or within 1 mm of tumour. The margins of the other patients were clear (≥8 mm).ConclusionThis study demonstrates the feasibility to detect tumour-positive resection margins with gGlu-HMRG and a clinical fluorescence imaging system. Applying this technique would enable intraoperative screening of the entire resection margin and allow direct re-resection in case of tumour-positivity.



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Local administration of Tiludronic Acid downregulates important mediators involved in periodontal tissue destruction in experimental periodontitis in rats

Publication date: Available online 9 January 2018
Source:Archives of Oral Biology
Author(s): Flávia A.C. Furlaneto, Nara L.T. Nunes, Ricardo B. Souza, Kely O. Yamamoto, Ivan L. Oliveira Filho, Nicolly P.R. Frota, Hellíada Chaves, Mario Lisboa, Mario Taba, Edilson Ervolino, Michel R. Messora
ObjectiveThe purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1β, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP).MethodsTwenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (C–Control group, EP–Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 μl of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL-1β, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1β, TNF-α, MMP-8 and COX-2 were immunohistochemically analyzed. Data were analyzed statistically.ResultsGroup EP-TIL presented reduced alveolar bone loss when compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA expressions of IL-1β, TNF-α, MMP-8 and COX-2 and reduced immunolabeling of IL-1β, TNF-α and MMP-8 when compared with group EP (p<0.05). No differences regarding the immunolabeling of COX-2 were found when group EP-TIL was compared with the other groups (p>0.05).ConclusionWithin the limits of this study, it can be concluded that local administration of TIL downregulates important mediators involved in periodontal tissue destruction in ligature-induced periodontitis in rats.



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CSACI position statement: prescribing sublingual immunotherapy tablets for aeroallergens

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ZmCCT9 enhances maize adaptation to higher latitudes [Plant Biology]

From its tropical origin in southwestern Mexico, maize spread over a wide latitudinal cline in the Americas. This feat defies the rule that crops are inhibited from spreading easily across latitudes. How the widespread latitudinal adaptation of maize was accomplished is largely unknown. Through positional cloning and association mapping, we...

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Retraction for Jayandharan et al., Activation of the NF-{kappa}B pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy [Retractions]

MEDICAL SCIENCES Retraction for "Activation of the NF-κB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy," by Giridhara R. Jayandharan, George Aslanidi, Ashley T. Martino, Stephan C. Jahn, George Q. Perrin, Roland W. Herzog, and Arun Srivastava, which was first published February 14,...

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Correction for Singh et al., Increasing potential for intense tropical and subtropical thunderstorms under global warming [Corrections]

EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Correction for "Increasing potential for intense tropical and subtropical thunderstorms under global warming," by Martin S. Singh, Zhiming Kuang, Eric D. Maloney, Walter M. Hannah, and Brandon O. Wolding, which was first published October 16, 2017; 10.1073/pnas.1707603114 (Proc Natl Acad Sci USA 114:11657–11662). The authors...

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ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells [Physiology]

N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown....

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Heat activation is intrinsic to the pore domain of TRPV1 [Physiology]

The TRPV1 channel is a sensitive detector of pain-producing stimuli, including noxious heat, acid, inflammatory mediators, and vanilloid compounds. Although binding sites for some activators have been identified, the location of the temperature sensor remains elusive. Using available structures of TRPV1 and voltage-activated potassium channels, we engineered chimeras wherein transmembrane...

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Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context [Neuroscience]

The memory for a new episode is formed immediately upon experience and can last up to a lifetime. It has been shown that the hippocampal network plays a fundamental role in the rapid acquisition of a memory of a one-time experience, in which the novelty component of the experience promotes...

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Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes [Neuroscience]

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and...

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ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations [Neuroscience]

ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including...

http://ift.tt/2qQzTm3

Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization [Microbiology]

Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial...

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Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria [Microbiology]

AAA+ disaggregases solubilize aggregated proteins and confer heat tolerance to cells. Their disaggregation activities crucially depend on partner proteins, which target the AAA+ disaggregases to protein aggregates while concurrently stimulating their ATPase activities. Here, we report on two potent ClpG disaggregase homologs acquired through horizontal gene transfer by the species...

http://ift.tt/2mdOnqt

Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes [Medical Sciences]

Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement....

http://ift.tt/2mlBewb

FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [Immunology and Inflammation]

FoxP3+ regulatory T cells (Tregs) are a central element of immunological tolerance. FoxP3 is the key determining transcription factor of the Treg lineage, interacting with numerous cofactors and transcriptional targets to determine the many facets of Treg function. Its absence leads to devastating lymphoproliferation and autoimmunity in scurfy mutant mice...

http://ift.tt/2qNQIOi

Low-lying excited states in crystalline perylene [Chemistry]

Organic materials are promising candidates for advanced optoelectronics and are used in light-emitting diodes and photovoltaics. However, the underlying mechanisms allowing the formation of excited states responsible for device functionality, such as exciton generation and charge separation, are insufficiently understood. This is partly due to the wide range of existing...

http://ift.tt/2CXhKZe

Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA [Biochemistry]

Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3′-5′ exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3′-end in vitro, and its...

http://ift.tt/2mj0seR

Inner Workings: Fishing for artifacts beneath the waves [Anthropology]

Fisherman Mike Anderson has accidentally hauled up all manner of oddities in his fishing gear—bits of pottery, lumps of coal, even a silver spoon. But he'd never seen anything like the heavy, jagged block pulled up by his scallop dredge as he cruised near the New England coast in the...

http://ift.tt/2qLfrTl

Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1 [Biochemistry]

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has...

http://ift.tt/2qKxGbJ

Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus [Microbiology]

Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in...

http://ift.tt/2mdUniH

Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy [Cell Biology]

PARKIN, an E3 ligase mutated in familial Parkinson's disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on...

http://ift.tt/2mj0nYB

High-resolution structure of podovirus tail adaptor suggests repositioning of an octad motif that mediates the sequential tail assembly [Biochemistry]

The sophisticated tail structures of DNA bacteriophages play essential roles in life cycles. Podoviruses P22 and Sf6 have short tails consisting of multiple proteins, among which is a tail adaptor protein that connects the portal protein to the other tail proteins. Assembly of the tail has been shown to occur...

http://ift.tt/2qM7m0O

RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases [Cell Biology]

Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell...

http://ift.tt/2qN9g0X

Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Multi-Envelope HIV-1 Vaccine Development: Two Targeted Immune Pathways, One Desired Protective Outcome

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2mbX9Fb

Ultrasound Identification of Diaphragm by Novices Using ABCDE Technique

Background and Objectives In this study, we examined the consistency, rapidity, and reproducibility of the ABCDE technique for diaphragm identification. Operators using this method place the probe at the Anterior axillary line, watch for Breathing (lung sliding), and then move the probe Caudally to identify the Diaphragm for Examination. Methods A convenience sample of 100 patients was recruited from the preadmission clinic. Two novice operators each scanned the diaphragm using a linear ultrasound transducer in B-mode. Both operators completed the examination on all participants using the ABCDE technique, their times were averaged, and clinical success was defined as identification of the diaphragm in less than 2 minutes. Results An average of 33.7 seconds was taken to scan and identify the right hemidiaphragm (RD) (median, 25 seconds; 95% confidence interval, 28.8–38.5 seconds) with a 98% clinical success ratio, and an average of 46.9 seconds was taken to identify the left hemidiaphragm (LD) (median, 39.5 seconds; 95% confidence interval, 40.2–53.6 seconds) with a 97% clinical success ratio. In patients with a body mass index (BMI) of less than 30 kg/m2, a 100% success ratio was seen when scanning the RD and 97% when scanning the LD. For those with a BMI of 30 kg/m2 or greater, a 94% success rate was seen when scanning the RD and 97% when scanning the LD. No clinically significant differences were found between the times required for scanning either side of the diaphragm, regardless of the BMI. Conclusions The ABCDE technique demonstrates a fast, reliable, and simple method in which ultrasound can be used to visualize the diaphragm. Accepted for publication September 2, 2017. Address correspondence to: Ban C.H. Tsui, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Dr, H3582, Stanford, CA 94305 (e-mail: bantsui@stanford.edu). This work was attributable to the Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada. B.C.H.T. is supported by a Clinical Scholar Award from the Alberta Heritage Foundation for Medical Research, Alberta, Canada; and J.K. is supported in part by an Alberta Health Services Surgery Strategic Clinical Network Summer Surgical Research Studentship Award, Alberta, Canada. The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Relative Contributions of Adductor Canal Block and Intrathecal Morphine to Analgesia and Functional Recovery After Total Knee Arthroplasty: A Randomized Controlled Trial

Background and Objectives Effective postoperative analgesia may enhance early rehabilitation after orthopedic surgery. This randomized double-blind trial investigates the relative contributions of adductor canal block and low-dose intrathecal morphine (ITM) to postoperative analgesia and functional recovery after total knee arthroplasty. Methods Two-hundred one patients undergoing elective unilateral total knee arthroplasty under spinal anesthesia were randomized to 3 groups. All patients received standardized intraoperative local infiltration analgesia and postoperative oral analgesics. Patients in group 1 received a "sham" adductor canal block with 30 mL of normal saline. Patients in group 2 received an adductor canal block with 30 mL of ropivacaine 0.5% with 1:400,000 epinephrine, whereas patients in group 3 received the adductor canal block with the active drug and 100 μg of ITM. The primary outcome measure was the Timed Up and Go (TUG) test on the second postoperative day. Secondary outcomes included postoperative pain scores and opioid requirements, distance walked, time to hospital discharge, and self-reported functional outcomes at 3 months. Results All 3 groups had similar values of TUG test on postoperative day (POD) 2 (46 [36–62], 45 [33–61], and 52 [41–69]; P = 0.166) as well as other short-term and 3-month functional outcomes. Patients in group 3 showed a favorable analgesic profile as evidenced by 3 positive secondary outcomes. These positive outcomes were lower pain scores 12 hours postoperatively both at rest (4 [2–6.3], 4 [2.3–6], and 3 [1–4]; P = 0.007) and on movement (6 [4–8], 6 [3–8], and 4 [2–6]; P = 0.002), a lower incidence of "rescue" intravenous patient-controlled analgesia (42%, 34%, and 20%; P = 0.031), and the lowest cumulative opioid requirements for the first 48 hours postoperatively (86 ± 71, 68 ± 46, and 59 ± 39; P

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Hate Crime Perpetrators: The Psychopath and the Perseverator

Violence and Gender , Vol. 0, No. 0.


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The Treatment of Antibody-Mediated Rejection in Kidney Transplantation: An Updated Systematic Review and Meta-Analysis

ABSTRACTBackgroundCurrent treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B-cells, plasma-cells and the complement system have featured in recent studies of AMR.MethodsWe conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE and CENTRAL from inception to February 2017.ResultsOf 14,380 citations we identified 21 studies, including 10 randomized controlled trials, involving 751 participants. Since the last systematic review conducted in 2011, we found 9 additional studies evaluating: plasmapheresis + intravenous immunoglobulin (IVIG) (2), rituximab (2), bortezomib (2), C1-inhibitor (2), and eculizumab (1). Risk of bias was serious or unclear overall and evidence quality was low for the majority of treatment strategies. Sufficient RCTs for pooled analysis were available only for antibody removal, and here there was no significant difference between groups for graft survival (HR 0.76; 95% CI 0.35–1.63; P=0.475). Studies showed important heterogeneity in treatments, definition of AMR, quality and follow-up. Plasmapheresis and IVIG were used as standard-of-care in recent studies, and to this combination, rituximab appeared to add little or no benefit. Insufficient data are available to assess the efficacy of bortezomib and complement inhibitors.ConclusionNewer studies evaluating Rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear. Despite the evidence uncertainty, plasmapheresis and IVIG have become standard-of-care for the treatment of acute AMR. Background Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B-cells, plasma-cells and the complement system have featured in recent studies of AMR. Methods We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE and CENTRAL from inception to February 2017. Results Of 14,380 citations we identified 21 studies, including 10 randomized controlled trials, involving 751 participants. Since the last systematic review conducted in 2011, we found 9 additional studies evaluating: plasmapheresis + intravenous immunoglobulin (IVIG) (2), rituximab (2), bortezomib (2), C1-inhibitor (2), and eculizumab (1). Risk of bias was serious or unclear overall and evidence quality was low for the majority of treatment strategies. Sufficient RCTs for pooled analysis were available only for antibody removal, and here there was no significant difference between groups for graft survival (HR 0.76; 95% CI 0.35–1.63; P=0.475). Studies showed important heterogeneity in treatments, definition of AMR, quality and follow-up. Plasmapheresis and IVIG were used as standard-of-care in recent studies, and to this combination, rituximab appeared to add little or no benefit. Insufficient data are available to assess the efficacy of bortezomib and complement inhibitors. Conclusion Newer studies evaluating Rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear. Despite the evidence uncertainty, plasmapheresis and IVIG have become standard-of-care for the treatment of acute AMR. Received 10 July 2017. Revision received 29 October 2017. Accepted 1 November 2017. CORRESPONDANCE: Professor Steve Chadban, Department of Renal Medicine, Royal Prince Alfred Hospital, Missenden Rd, Camperdown NSW 2050, Australia. E: Steve.Chadban@health.nsw.gov.au AUTHORSHIP - Susan Wan – Research design, study protocol preparation, performed search and study selection, data synthesis and manuscript preparation - Tracey Ying – Research design, study protocol preparation, performed search and study selection, data synthesis and manuscript preparation - Kate Wyburn – Research design, data review and manuscript preparation - Darren Roberts – Research design and manuscript preparation - Melanie Wyld – Research design and manuscript preparation - Steve Chadban – Research design, data review and manuscript preparation All authors approved the final manuscript DISCLOSURE The authors declare no conflicts of interest FUNDING SW is funded by the Royal Australasian College of Physicians (RACP) Jacquot Research Entry Scholarship for her postdoctoral studies TY is funded by the Australian Postgraduate Award for her postdoctoral studies Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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High intrapatient variability of tacrolimus exposure in the early period after liver transplantation is associated with poorer outcomes

AbstractBackgroundTacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high inter- and intrapatient variability leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC intrapatient variability (IPV) on graft and patient outcomes after liver transplantation.MethodsWe retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV

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Pockmarks: Treatments and home remedies

There are a number of treatments and home remedies that may help reduce the appearance of the scars and improve the look and feel of the skin.

http://ift.tt/2CWWaDu

Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma

Publication date: Available online 8 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Yuka Asai, Aida Eslami, C. Dorien van Ginkel, Loubna Akhabir, Ming Wan, David Yin, George Ellis, Moshe Ben-Shoshan, Ingo Marenholz, David Martino, Manuel A. Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W. de Jong, Roy Gerth van Wijk, Anthony E.J. Dubois, Sarah Grosche, Sarah Ashley, Franz Rüschendorf, Birgit Kalb, Kirsten Beyer, Markus M. Nöthen, Young-Ae Lee, Rick Chin, Steven Cheuk, Joshua Hoffman, Eric Jorgensen, John S. Witte, Ronald B. Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W. (Bill) Musk, Michael Hunter, Alan L. James, Gerard H. Koppelman, Andrew J. Sandford, Ann E. Clarke, Denise Daley




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A functional splicing variant associated with decreased asthma risk abolishes the ability of gasdermin B (GSMDB) to induce epithelial cell pyroptosis

Publication date: Available online 9 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ronald A. Panganiban, Maoyun Sun, Amber Dahlin, Hae-Ryung Park, Mengyuan Kan, Blanca E. Himes, Jennifer A. Mitchel, Carlos Iribarren, Eric Jorgenson, Scott H. Randell, Elliot Israel, Kelan Tantisira, Stephanie Shore, Jin-Ah Park, Scott T. Weiss, Ann Chen Wu, Quan Lu
BackgroundGenetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive.ObjectivesWe sought to identify and characterize functional variants in the 17q21 locus. Methods: We used the Exome Aggregation Consortium (ExAC) browser to identify coding (amino acid-changing) variants in the 17q21 locus. We obtained asthma association measures for these variants in both the GERA cohort (16,274 cases and 38,269 matched controls) and the EVE Consortium study (5,303 asthma cases and 12,560 individuals). Gene expression and protein localization were determined by quantitative RT-PCR and fluorescence immunostaining, respectively. Molecular and cellular studies were performed to determine the functional effects of coding variants.ResultsTwo coding variants (rs2305480 and rs11078928) of the gasdermin B (GSDMB) gene in the 17q21 locus were associated with lower asthma risk in both GERA (OR = 0.92; P= 1.01 × 10^-6) and EVE (OR= 0.85; Joint PEVE = 1.31 ×10^-13). In GERA, rs11078928 had a minor allele frequency (MAF) of 0.45 in unaffected (non-asthmatic) controls and 0.43 in asthma cases. For European Americans in EVE the MAF of rs2305480 was 0.45 for controls and 0.39 for cases; for all EVE subjects the MAF was 0.32 for controls and 0.27 for cases. GSDMB is highly expressed in differentiated airway epithelial cells, including the ciliated cells. We found that when the GSDMB protein is cleaved by inflammatory caspase-1 to release its N-terminal fragment, potent pyroptotic cell death was induced. The splicing variant rs11078928 deletes the entire exon 6, which encodes 13 amino acids in the critical N-terminus, and abolishes the pyroptotic activity of the GSDMB protein.ConclusionsOur study identified a functional asthma variant in the GSDMB gene of the 17q21 locus and implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis.

Graphical abstract

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Oncomodulin Expression Reveals New Insights into the Cellular Organization of the Murine Utricle Striola

Abstract

Oncomodulin (OCM, aka β-parvalbumin) is an EF-hand calcium binding protein that is expressed in a restricted set of hair cells in the peristriolar region of the mammalian utricle. In the present study, we determined the topologic distribution of OCM among hair cell phenotypes to advance our understanding of the cellular organization of the striola and the relationship of these phenotypes with characteristics of tissue polarity. The distributions of OCM-positive (OCM+) hair cells were quantified in utricles of mature C57Bl/6 mice. Immunohistochemistry was conducted using antibodies to OCM, calretinin, and β3-tubulin. Fluorophore-conjugated phalloidin was used to label hair cell stereocilia, which provided the basis for determining hair cell counts and morphologic polarizations. We found OCM expression in striolar types I and II hair cells, though the distributions were dissimilar to the native striolar type I and II distributions, favoring type I hair cells. The distribution of OCM immunoreactivity among striolar type I hair cells also reflected nonrandom distribution among type I_c and I_d phenotypes (i.e., those receiving calretinin-positive and calretinin-negative calyces, respectively). However, many OCM+ hair cells were found lateral to the striola, and within the epithelial region encompassing OCM+ hair cells, the distributions of OCM+ types I_c and I_d hair cells were similar to the native distributions of I_c and I_d in this region. Summarily, these data provide a quantitative perspective supporting the existence of different underlying factors driving the topologic expression of OCM in hair cells than those responsible for tissue polarity characteristics associated within the utricular striola, including calretinin expression in afferent calyces.

http://ift.tt/2Eqh9M2

Oncomodulin Expression Reveals New Insights into the Cellular Organization of the Murine Utricle Striola

Abstract

Oncomodulin (OCM, aka β-parvalbumin) is an EF-hand calcium binding protein that is expressed in a restricted set of hair cells in the peristriolar region of the mammalian utricle. In the present study, we determined the topologic distribution of OCM among hair cell phenotypes to advance our understanding of the cellular organization of the striola and the relationship of these phenotypes with characteristics of tissue polarity. The distributions of OCM-positive (OCM+) hair cells were quantified in utricles of mature C57Bl/6 mice. Immunohistochemistry was conducted using antibodies to OCM, calretinin, and β3-tubulin. Fluorophore-conjugated phalloidin was used to label hair cell stereocilia, which provided the basis for determining hair cell counts and morphologic polarizations. We found OCM expression in striolar types I and II hair cells, though the distributions were dissimilar to the native striolar type I and II distributions, favoring type I hair cells. The distribution of OCM immunoreactivity among striolar type I hair cells also reflected nonrandom distribution among type I_c and I_d phenotypes (i.e., those receiving calretinin-positive and calretinin-negative calyces, respectively). However, many OCM+ hair cells were found lateral to the striola, and within the epithelial region encompassing OCM+ hair cells, the distributions of OCM+ types I_c and I_d hair cells were similar to the native distributions of I_c and I_d in this region. Summarily, these data provide a quantitative perspective supporting the existence of different underlying factors driving the topologic expression of OCM in hair cells than those responsible for tissue polarity characteristics associated within the utricular striola, including calretinin expression in afferent calyces.

http://ift.tt/2Eqh9M2

Strategies for a regenerative therapy of hearing loss

Abstract

Despite impressive technical progress in the field of conventional hearing aids and implantable hearing systems, the hopes for the treatment of inner ear diseases such as hearing loss and tinnitus have become increasingly directed toward regenerative therapeutic approaches. This review discusses the currently most promising strategies for hair cell regeneration in the inner ear to treat hearing loss, including stem cell-based, gene transfer-based, and pharmacological interventions. Furthermore, previous milestones and ground-breaking work in this scientific field are identified. After many years of basic research, the first clinical trials with a regenerative therapeutic approach for hearing-impaired patients were recently initiated. Although there is still a long and bumpy road ahead until a true breakthrough is achieved, it seems more realistic than ever that regenerative therapies for the inner ear will find their way into clinical practice.

http://ift.tt/2DaYRPd

Slave codes and penal laws in eighteenth-century Jamaica and Ireland: a comparative and historiographical survey

Graham, AB; (2018) Slave codes and penal laws in eighteenth-century Jamaica and Ireland: a comparative and historiographical survey. Jamaican Historical Review (In press).

http://ift.tt/2ErEhcV

Together we innovate: Cross-cultural teamwork through virtual platforms

Duus, R; Cooray, M; (2014) Together we innovate: Cross-cultural teamwork through virtual platforms. Journal of Marketing Education , 36 (3) pp. 244-257. 10.1177/0273475314535783 .

http://ift.tt/2Fidf94

Influence of feed/inoculum ratios and waste cooking oil content on the mesophilic anaerobic digestion of food waste

Li, Y; Jin, Y; Borrion, A; Li, J; (2018) Influence of feed/inoculum ratios and waste cooking oil content on the mesophilic anaerobic digestion of food waste. Waste Management 10.1016/j.wasman.2017.12.027 . (In press).

http://ift.tt/2EpaIIV

A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis

Bielecka, MK; Tezera, LB; Zmijan, R; Drobniewski, F; Zhang, X; Jayasinghe, S; Elkington, P; (2017) A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis. mBio , 8 (1) , Article e02073-16.. 10.1128/mBio.02073-16 . Green open access

http://ift.tt/2FmoUny

Higher education research in the Asia-Pacific

Huang, F; Marginson, S; (2017) Higher education research in the Asia-Pacific. International Journal of Educational Development 10.1016/j.ijedudev.2017.10.008 . (In press).

http://ift.tt/2Epwkow

Internet-accessed sexually transmitted infection (e-STI) testing and results service: A randomised, single-blind, controlled trial

Wilson, E; Free, C; Morris, TP; Syred, J; Ahamed, I; Menon-Johansson, AS; Palmer, MJ; ... Baraitser, P; + view all Wilson, E; Free, C; Morris, TP; Syred, J; Ahamed, I; Menon-Johansson, AS; Palmer, MJ; Barnard, S; Rezel, E; Baraitser, P; - view fewer (2017) Internet-accessed sexually transmitted infection (e-STI) testing and results service: A randomised, single-blind, controlled trial. PLoS Medicine , 14 (12) , Article e1002479. 10.1371/journal.pmed.1002479 . Green open access

http://ift.tt/2FifQjn

Use of LysoTracker Dyes: A Flow Cytometric Study of Autophagy

Chikte, S; Panchal, N; Warnes, G; (2013) Use of LysoTracker Dyes: A Flow Cytometric Study of Autophagy. Cytometry Part A , 85 (2) pp. 169-178. 10.1002/cyto.a.22312 .

http://ift.tt/2Epw2xW

Developing a non-invasive tool to assess the impact of oxidation on the structural integrity of historic wool in Tudor tapestries

Kissi, N; Curran, K; Vlachou-Mogire, C; Fearn, T; McCullough, L; (2017) Developing a non-invasive tool to assess the impact of oxidation on the structural integrity of historic wool in Tudor tapestries. Heritage Science , 5 (49) 10.1186/s40494-017-0162-1 . Green open access

http://ift.tt/2Fi83lF

Cannabis Use and Hypomania in Young People: A Prospective Analysis

Marwaha, S; Winsper, C; Bebbington, P; Smith, D; (2017) Cannabis Use and Hypomania in Young People: A Prospective Analysis. Schizophrenia Bulletin 10.1093/schbul/sbx158 . (In press). Green open access

http://ift.tt/2Eqqe7k

Digital Back-propagation for Unrepeatered Transmission

Lavery, DJP; (2017) Digital Back-propagation for Unrepeatered Transmission. In: IEEE: Switzerland, Cham. (In press).

http://ift.tt/2Fj0GdB

The public good created by higher education institutions in Russia

Marginson, S; (2017) The public good created by higher education institutions in Russia. Voprosy Obrazovaniya/Educational Studies (Moscow) , 2017 (3) pp. 9-36. 10.17323/1814-9545-2017-3-8-36 .

http://ift.tt/2ErZoMq

Patient-specific simulations for planning treatment in congenital heart disease

Capelli, C; Sauvage, E; Giusti, G; Bosi, GM; Ntsinjana, H; Carminati, M; Derrick, G; ... Schievano, S; + view all Capelli, C; Sauvage, E; Giusti, G; Bosi, GM; Ntsinjana, H; Carminati, M; Derrick, G; Marek, J; Khambadkone, S; Taylor, AM; Schievano, S; - view fewer (2018) Patient-specific simulations for planning treatment in congenital heart disease. Interface Focus , 8 (1) , Article 20170021. 10.1098/rsfs.2017.0021 . Green open access

http://ift.tt/2FhTMp9

A 32x10 Gb/s OLT Using a Single Ultra-wide Bandwidth Dual Local Oscillator Coherent Receiver

Lavery, DJP; (2017) A 32x10 Gb/s OLT Using a Single Ultra-wide Bandwidth Dual Local Oscillator Coherent Receiver. In: IEEE: Switzerland, Cham. (In press).

http://ift.tt/2EobNRl

Vanadium Compounds as PTP Inhibitors

Irving, E; Stoker, AW; (2017) Vanadium Compounds as PTP Inhibitors. Molecules , 22 (12) , Article 2269. 10.3390/molecules22122269 . Green open access

http://ift.tt/2Fi6c02

Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and bronchiolitis severity

Abstract

Low circulating 25-hydroxyvitamin D (25OHD) levels are a risk factor for acute respiratory infection (e.g., bronchiolitis) in children. However, little is known about the relation of circulating 25OHD with the many downstream functional molecules in target organs – such as the airway – and with clinical outcomes. In this prospective multicenter study of infants (age <1 year) hospitalized with bronchiolitis, we measured serum 25OHD levels and profiled the metabolome of 144 nasopharyngeal airway samples. Among 254 metabolites identified, we defined a set of 20 metabolites that are related to lower serum 25OHD and higher vitamin D-binding protein levels. Of these metabolites, 9 metabolites were associated with a significantly higher risk of positive pressure ventilation use. These metabolites were glycerophosphocholines esterified with proinflammatory fatty acids (palmitate, arachidonate, linoleate, and stearate), sphingomyelins, alpha-hydroxyisovalerate, 2-hydroxybutyrate, and 3-(4-hydroxyphenyl)lactate (all FDR<0.05). Based on the multicenter data, vitamin D-related airway metabolites were associated with risks of bronchiolitis severity.

This article is protected by copyright. All rights reserved.

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TNF Family Member LIGHT Acts with IL-1β and TGF-β to Promote Airway Remodeling During Rhinovirus Infection

Abstract

Background

Rhinovirus (RV) can exacerbate allergen-driven asthma. However, it has been suggested that serial infections with RV may also lead to asthma-like features in childhood without prior allergen exposure.

Aim

We sought to test the effects of RV infection in the absence of allergen challenge on lung tissue remodeling and to understand if RV induced factors in common with allergen that promote remodeling.

Methods

We infected C57BL/6 mice multiple times with RV in the absence or presence of allergen to assess airway remodeling. We used knockout mice and blocking reagents to determine the participation of LIGHT (TNFSF14), as well as IL-1β and TGF-β, each previously shown to contribute to lung remodeling driven by allergen.

Results

Recurrent RV infection without allergen challenge induced an increase in peribronchial smooth muscle mass and subepithelial fibrosis. RV induced LIGHT expression in mouse lungs after infection, and alveolar epithelial cells and neutrophils were found to be potential sources of LIGHT. Accordingly, LIGHT-deficient mice, or mice where LIGHT was neutralized, displayed reduced smooth muscle mass and lung fibrosis. Recurrent RV infection also exacerbated the airway remodeling response to house dust mite allergen and this was significantly reduced in LIGHT deficient mice. Furthermore, neutralizing IL-1β or TGF-β also limited subepithelial fibrosis and/or smooth muscle thickness induced by RV.

Conclusion

Rhinovirus can promote airway remodeling in the absence of allergen through upregulating common factors that also contribute to allergen-associated airway remodeling.

This article is protected by copyright. All rights reserved.

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Food allergen-sensitized CCR9+ lymphocytes enhance airways allergic inflammation in mice

Abstract

Background

The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors.

Objectives

We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases.

Methods: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite.

Results

Compared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/ Treg ratio, was abrogated in CCR9 knock-out mice. Moreover, transfer of food-allergic CD4+ T cells from wild-type but not from CCR9-/- aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens.

Conclusion

Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.

This article is protected by copyright. All rights reserved.

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Isolation of a high affinity Bet v 1-specific IgG-derived ScFv from a subject vaccinated with hypoallergenic Bet v 1 fragments

Abstract

Background

Recombinant hypoallergenic allergen derivatives have been used in clinical immunotherapy studies and clinical efficacy seems to be related to the induction of blocking IgG antibodies recognizing the wild type allergens. However, so far no treatment-induced IgG antibodies have been characterized.

Objective

To clone, express and characterize IgG antibodies induced by vaccination with two hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1 in a non-allergic subject.

Methods

A phage-displayed combinatorial single chain fragment (ScFv) library was constructed from blood of the immunized subject and screened for Bet v 1-reactive antibody fragments. ScFvs were tested for specificity and cross-reactivity to native Bet v 1 and related pollen and food allergens and epitope mapping was performed. Germline ancestor genes of the antibody were analyzed with the ImMunoGeneTics (IMGT) database. The affinity to Bet v 1 and cross-reactive allergens was determined by surface plasmon resonance measurements. The ability to inhibit patients' IgE binding to ELISA plate-bound allergens and allergen-induced basophil activation was assessed.

Results

A combinatorial ScFv library was obtained from the vaccinated donor after three injections with the Bet v 1 fragments. Despite being almost in germline configuration, ScFv (clone H3-1) reacted with high affinity to native Bet v 1 and homologous allergens, inhibited allergic patients' polyclonal IgE binding to Bet v 1 and partially suppressed allergen-induced basophil activation.

Conclusion

Immunization with unfolded hypoallergenic allergen derivatives induces high affinity antibodies even in non-allergic subjects which recognize the folded wild-type allergens and inhibit polyclonal IgE binding of allergic patients.

This article is protected by copyright. All rights reserved.

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In chronic spontaneous urticaria, IgE against staphylococcal enterotoxins is common and functional

Abstract

Background

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema. Despite the known effectiveness of omalizumab therapy, the relevant IgE antigens are largely unknown. Recently, increased rates of elevated levels of IgE towards Staphylococcus aureus enterotoxins (SEs) were described in CSU.

Aim

To assess the prevalence and functional relevance of IgE to SEs in CSU.

Method: We investigated serum levels of IgE against SEs in 49 CSU patients and in 15 CSU patients additional specific IgE to SE components and basophil histamine release (BHR). Sera of15 healthy controls (HCs) served as control group.

Results

25 (51%) of the CSU patients had detectable levels of SE-IgE as compared to 5 (33%) of HCs. Specific IgE to one of the SEs, Staphylococcus enterotoxin B (SEB), was present in 5 (33%) of 15 randomly selected CSU patients vs 3 (20%) of HC. Total IgE serum levels in CSU patients were significantly correlated with SE-IgE (r = 0.52, p<0.001) and SEB-IgE (r = 0.54, p = 0.04) serum concentrations. Interestingly, SEB-IgE levels were strongly correlated with disease activity (UASday) in CSU patients (r=0.657, p=0.01). Furthermore, BHR in response to SEB was significantly higher in basophils loaded with the serum of CSU patients compared to HC (p<0.05) and was clinically correlated with duration of disease (r >0.51, p <0.05).

Discussion

IgE against SEs may contribute to the pathogenesis of CSU in a subpopulation of patients Its role and relevance in the pathophysiology of CSU needs to be further analysed.

This article is protected by copyright. All rights reserved.

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Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis

Abstract

Background

The purpose of this study was to examine the possible prognostics and clinicopathologic characteristics underlying the BRAFV600E mutation and papillary thyroid carcinoma (PTC) coexisting or in absence of chronic lymphocytic thyroiditis (CLT).

Methods

This study was conducted on 172 patients who had undergone total thyroidectomy or unilateral total thyroidectomy for PTC; the patients were then examined for the BRAFV600E mutation using specimens obtained after their surgery from January 2013 to August 2015.

Results

BRAF mutations were found in 130 of 172 patients (75.6%). CLT was present in 27.9% of patients (48/172). The incidence of the BRAFV600E mutation was significantly increased in the group with no CLT (P = 0.001). The findings of the multivariate analysis pertaining to the coexistence of CLT and PTC showed no significant correlation other than the BRAFV600E mutation. No significant difference was noted in the clinicopathologic factors between the two groups based on the coexistence of CLT in univariate and multivariate analyses.

Conclusions

The BRAFV600E mutation is less frequent in PTC coexisting with CLT presumably because CLT and the BRAFV600E mutation operate independently in the formation and progression of thyroid cancer.

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Acquired idiopathic generalized anhidriosis: Successful treatment with cyclosporine in two cases

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Left Ventricular Assist Device Implantation with Concomitant Aortic Valve and Ascending Aortic Replacement

Left ventricular assist device (LVAD) is nowadays a routine therapy for patients with advanced heart failure. We present the case of a 74-year-old male patient who was admitted to our center with terminal heart failure in dilated cardiomyopathy and ascending aortic aneurysm with aortic valve regurgitation. The LVAD implantation with simultaneous aortic valve and supracoronary ascending aortic replacement was successfully performed.

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IRF1 up-regulates isg15 gene expression in dsRNA stimulation or CSFV infection by targeting nucleotides −487 to −325 in the 5′ flanking region

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Xiao-Quan Li, Xiao Ning Li, Jing-Jing Liang, Xin-Bin Cai, Qian Tao, Yu-Xiao Li, Qing Qin, Su-Ping Xu, Ting Rong Luo
Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5′ flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al., 2015), but the mechanism is not well understood. Herein, we report that porcine IRF1 and ISG15 were up-regulated in porcine kidney (PK-15) cells following stimulation with double-stranded RNA (dsRNA) or classical swine fever virus (CSFV) infection. We also found that siRNA-mediated knockdown of IRF1 expression resulted in lower ISG15 expression in response to polyinosinic:polycytidylic acid [poly(I:C)] or CSFV infection. The overexpression of IRF1 resulted in ISG15 up-regulation. IRF1 was shown to translocate to the nucleus in response to dsRNA stimulation. To further identify the functional domain of the isg15 gene that promotes IRF1 transcriptional activity, firefly luciferase and ISG15 reporter systems were constructed. The results of the firefly luciferase and ISG15 reporter assay suggested that IRF1 mediates the up-regulation of ISG15. Nucleotides −487 to −325, located in the 5′ flanking region of the isg15 gene, constituted the promoter region of IRF1. ChIP assay indicated that IRF1 protein was able to interact with the DNA in the 5′fr of isg15 gene in cells. As an innate immune response protein with broad-spectrum antiviral activity, the up-regulation of ISG15 mediated by IRF1 in porcine cells is reported for the first time. These results warrant further investigation into the antiviral activity of porcine IRF1 against reported swine viruses.



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DNA induction of MDM2 promotes proliferation of human renal mesangial cells and alters peripheral B cells subsets in pediatric systemic lupus erythematosus

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Chen-xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-yuan Wang, Lan-fang Cao, Wei Zhou, Tong-xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4⁺T, CD8⁺T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC). We also proved that elevated apoptotic and necrotic CD4⁺T cells were the main cause for increased plasma levels of cfDNA in pSLE. Additionally, upon DNA transfection MDM2 increased while P53 and P21 decreased in human renal mesangial cells (HRMC), with concomitant increase in proliferation rate and proportion of cells in S phase, as demonstrated by cell proliferation assay and cell cycle analysis. However, MDM2 inhibition reversed the trend. Furthermore, percentage of switched memory B cells decreased and proportion of double negative B cells increased upon blockage of MDM2 in PBMC. In summary, our study provided the first evidence that DNA induction of MDM2 promotes proliferation of HRMC and alters peripheral B cells subsets in pSLE. Thus our study has not only elucidated the pathogenesis of MDM2 in pediatric LN but also provided a novel target for drug development. In conclusion, our data suggested that apoptosis, cfDNA and MDM2 could form a pathological axis in SLE, especially in pSLE.



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Immunization with recombinant FliD confers protection against Helicobacter pylori infection in mice

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Amir Ghasemi, Nazanin Mohammad, Josef Mautner, Mehrnaz Taghipour Karsabet, Abolfazl Ardjmand, Rezvan Moniri
Nearly half of the world's population is infected with Helicobacter pylori. Clinical manifestations of this infection range from gastritis and peptic ulcers to gastric adenocarcinoma and lymphoma. Due to the emerging of antibiotic resistant strains and poor patient compliance of the antibiotic therapy, there is increasing interest in the development of a protective vaccine against H. pylori infection. The bacterial protein FliD forms a capping structure on the end of each flagellum which is critical to prevent depolymerization and structural degradation. In this study, the potential of FliD as a prospective H. pylori subunit vaccine was assessed. For this purpose, immunogenicity and protective efficacy of recombinant FliD (rFliD) from H. pylori was evaluated in C57BL/6 mice. Purified rFliD was formulated with different adjuvants and administered via subcutaneous or oral route. Subcutaneous immunization with rFliD elicited predominantly mixed Th1 and Th17 immune responses, with high titers of specific IgG1 and IgG2a. Splenocytes of immunized mice exhibited strong antigen-specific memory responses, resulting in the secretion of high amounts of IFN-γ and IL-17, and low levels of IL-4. Immunization with rFliD caused a significant reduction in H. pylori bacterial load relative to naïve control mice (p < 0.001), demonstrating a robust protective effect. Taken together, these results suggest that subcutaneous vaccination with rFliD formulated with CpG or Addavax could be considered as a potential candidate for the development of a subunit vaccine against H. pylori infection.



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The emerging role of nanomaterials in immunological sensing — a brief review

Publication date: Available online 8 January 2018
Source:Molecular Immunology
Author(s): Simon R. Corrie, Magdalena Plebanski
Nanomaterials are beginning to play an important role in the next generation of immunological assays and biosensors, with potential impacts both in research and clinical practice. In this brief review, we highlight two areas in which nanomaterials are already making new and important contributions in the past 5–10 years: firstly, in the improvement of assay and biosensor sensitivity for detection of low abundance proteins of immunological significance, and secondly, in the real-time and continuous monitoring of protein secretion from arrays of individual cells. We finish by challenging the immunology/sensing communities to work together to develop nanomaterials that can provide real-time, continuous, and sensitive molecular readouts in vivo, a lofty goal that will require significant collaborative effort.



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Issue Information

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55 Year-old Patient with Intranasal Mass

Abstract

The patient is a 55 year old female who presented with a right sided intranasal mass in 2014. Surgery was recommended, but the patient cancelled the surgery. She returned three years later with a significant progression of the lesion. What is this lesion and how would you manage it?

Five months after resection of the lesion, the patient returns with pulsatile clear mucus visible on nasal endoscopy in the region of the prior mass excision. What does this represent and how should we proceed at this point? Is the patient developing a meningo-encephalocele? 

http://ift.tt/2CH78cN

Mondor’s disease – a rare cause of chest pain: a case report

Chest pain is one of the common presenting symptoms encountered in an emergency department. Prompt history taking and careful clinical examination do help to differentiate cardiac chest pain from other causes....

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StrataXRT vs Standard Clinical Practice for the Prevention of Acute Dermatitis in Head and Neck Cancers Patients

Conditions:   Head and Neck Cancers;   Acute Radiation Dermatitis
Intervention:   Device: StrataXRT
Sponsor:   National University Hospital, Singapore
Not yet recruiting

http://ift.tt/2EqAxsn

A Topology of Shared Control Systems – Finding Common Ground in Diversity

Abbink, DA; Carlson, T; Mulder, M; de Winter, JCF; Aminravan, F; Gibo, TL; Boer, ER; (2018) A Topology of Shared Control Systems – Finding Common Ground in Diversity. IEEE Transactions on Human-Machine Systems (In press).

http://ift.tt/2m8gV4y

Carers’ experiences of home enteral feeding: a survey exploring medicines administration challenges and strategies

Alsaeed, D; Furniss, D; Blandford, A; Smith, F; Orlu, M; (2018) Carers' experiences of home enteral feeding: a survey exploring medicines administration challenges and strategies. Journal of Clinical Pharmacy and Therapeutics (In press).

http://ift.tt/2D9GElb

Issue Information

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Neuroendokrine Tumoren aus psychoonkologischer Sicht – ein Überblick

Zusammenfassung

In aller Regel besteht bei Patienten mit neuroendokrinen Tumoren (NET) ein langwieriger Verlauf, der bereits lange vor Diagnosestellung beginnt. Sie müssen mit viel Ungewissheit umgehen. Dennoch lassen sich allgemeine Aussagen zur Lebensqualität (LQ) und psychischen Verfassung von Patienten mit NET schwer treffen. Zum einen ist NET ein Oberbegriff für eine heterogene Gruppe von Tumoren, die sich in ihrem klinischen Erscheinungsbild stark unterscheiden. Somit gibt es zwangsläufig innerhalb der Gruppe von Patienten mit NET erhebliche Unterschiede in den Belastungen und der LQ. Zum anderen gibt es bislang in der Literatur nur wenige hochwertige Studien, die mittels validierter und NET-spezifischer Messverfahren die LQ bzw. Belastungen von Patienten mit NET analysieren. Um besonders belastete Patienten zu identifizieren, ist eine differenzierte Betrachtung der LQ von Patienten mit NET erforderlich. Nur dann lassen sich auch klinisch relevante Schlüsse ableiten. Für Patienten mit psychischen Belastungen gibt es verschiedene evidenzbasierte Behandlungsmöglichkeiten.

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Psychosoziale Aspekte von Harnblasenkarzinompatienten

Zusammenfassung

Tumorpatienten müssen sich mit dem Gefühl der Unsicherheit hinsichtlich des weiteren Lebens und Krankheitsverlaufs sowie mit unerwünschten Nebenwirkungen der Therapie auseinandersetzen. Niedrige Lebensqualität ist bei krebskranken Patienten ein unabhängiger prognostischer Faktor für geringere Überlebensraten. Psychosozialer Stress beeinflusst negativ das Immunsystem (Reduktion der NK-Zellen, Anstieg des Cortisolspiegels). Trotz verbesserter Diagnostik und Therapie bleibt das Blasenkarzinom durch hohe Rezidiv- und Progressionshäufigkeit gekennzeichnet. Für die Behandlung eines Harnblasentumors werden, je nach Tumorstadium, verschiedene therapeutische Maßnahmen empfohlen, die sich auf die Lebensqualität auswirken können. Studien über die psychosozialen Bedürfnisse von Patienten mit Harnblasenkarzinom sind vergleichsweise selten.

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Physics’ silence on time

Abstract

In this paper I argue that physics is, always was, and probably always will be voiceless with respect to tense and passage, and that, therefore, if, as I believe, tense and passage are the essence of time, physics' contribution to our understanding of time can only be limited. The argument, in a nutshell, is that if "physics has no possibility of expression for the Now", to quote Einstein, then it cannot add anything to the study of tense and passage, and specifically, cannot add anything to the debate between deniers and affirmers of the existence or reality of tense and passage. Since relativity theory did not equip physics with a new language with which to speak of tense and passage, I draw the further conclusion that relativity theory has not generated the revolution to our conception of time that is attributed to it. In the last section I discuss the motivations behind the continued but misguided attempts to integrate tense into a relativistic setting, and assess the manners in which relativity theory has nevertheless enhanced, albeit indirectly, our understanding of tense and passage.

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Making a Difference

By Nathan Douthit

Global Health Case Reports (GHCR) at BMJ Case Reports can help practitioners of global health in all settings, cultures and situations. These practitioners are doctors, nurses, social workers, students, dentists and others who care about those missed by more traditional healthcare models. They seek to treat the patient but also to change the true causes of their disease—the social determinants of health.

Global Health has three core facets. Global health is global in scope; it crosses international and local barriers. Global health is global in focus; it addresses the whole patient's well-being physically, socially, mentally, and environmentally. Global health is global in approach; it requires interventions from teams composed of multiple disciplines in order to address the issues faced by individuals and communities.

GHCRs address the scope of global health. They can address the barriers of conflict as in "Complications of dysgerminoma: meeting the health needs of patients in conflict zones," as well as opportunities and models for overcoming these barriers. In this case, a young woman from a country torn by conflict is treated in a neighboring country. Due to concern that she would not receive appropriate care due the devastation of her country's infrastructure, "it was agreed that the patient remain in this hospital for chemotherapy as it was unlikely that treatment would have been possible in her home country." The doctors and hospital administrators went above and beyond to ensure that the patient received appropriate treatment.

The focus of global health can be seen in GHCRs. As "HIV in India: the Jogini culture" shows, patients require more than healthcare to improve their social standing; access to education and economic viability are also essential. The Non-governmental organisation that brought her to the hospital for medical care also, "advocated for her to the government and helped her to understand her rights to a pension and a home as legal entitlements of all former Jogini." They had to address the determinants of her health in order to ensure that she would not return to the same conditions that made her ill in the first place.

To be successful in global health, a multidisciplinary approach is necessary. Excellent examples of these approaches can be seen in GHCRs. "Family as the primary caregiver: palliative care in the Golan Heights" describes the need for a community to gather around the patient to equip them to meet their needs. Input is needed from many disciplines to have a successful outcome. The physicians went above and beyond to ensure that the father was trained to care for the patient; in addition to weekly visits they made themselves, "available for contact at any time, in case of emergency." Nursing staff visited the family 2 times per week, and, "a social worker was available to the family to aid with non-medical and bureaucratic issues." This commitment to the patient enabled the healthcare staff to facilitate, "emotional healing of the family and the village in a way that could not have been accomplished far from home, in the halls of the closest hospital."

In 2018, BMJ Case Reports has chosen the theme of "Making a Difference." For GHCRs, this theme will be emphasized to show how global health case reports can change the lives of patients and practitioners. Global healthcare providers advocate for change, educate patients and practitioners, and most importantly are willing to go above and beyond the ordinary limits of medical practice in order to make a difference in the lives of their patients. We will be highlighting the ways these practitioners make a difference through global health in the coming year. Check the blog frequently for more updates on this theme, join us by writing a case report for a global health patient, and follow our social media accounts for more information.

Competing Interests

None Declared

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Etoposide as a single agent in the treatment of mycosis fungoides: A retrospective analysis

Abstract

Several chemotherapy agents have shown efficacy in the treatment of mycosis fungoides (MF). In the literature, there is limited data on the use of single agent etoposide for MF. We aimed to retrospectively review our experience with single agent etoposide in the treatment of advanced-stage or refractory early-stage MF with focus on analyzing its efficacy and safety. We included 13 MF patients who were treated with single agent etoposide. Patients were identified through the Cutaneous T Cell Lymphoma Database of Indiana University that involves patients treated from 2006 to 2016. Overall nine patients (69%) responded to treatment. No complete response was identified. Median time to response was 12.5 weeks (range: 6–25.4). Median duration of response was 43 weeks (range: 5–60) and median time to treatment failure was 31.3 weeks (range: 12.4–230). Hematological toxicity was observed in eight patients including two patients with grade 4 neutropenia and/or lymphopenia leading to sepsis. Higher doses of etoposide were significantly correlated with higher grades of anemia, neutropenia or lymphopenia (p < .05). Our study demonstrates that etoposide is an effective treatment for MF and may be considered in selected patients with progressive MF who have failed other treatments.

http://ift.tt/2AKII0o

Management of Persistent Epistaxis Using Floseal Hemostatic Matrix vs. traditional nasal packing: a prospective randomized control trial

Epistaxis is the most common emergent consultation to otolaryngology-head & neck surgery (OHNS) and with 60% of the population having experienced an episode and 1.6 in 10,000 requiring hospitalization in their...

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Head and Neck Surgical Oncology Choosing Wisely Campaign: imaging for patients with hoarseness, fine needle aspiration for neck mass, and ultrasound for odynophagia

Choosing Wisely Canada, is a campaign designed to raise awareness regarding inappropriate or unnecessary tests and treatments. The Canadian Society of Otolaryngology - Head & Neck Surgery and the Canadian Asso...

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Correction: Der physiologische und der pathologische Schluckvorgang

Correction:

HNO 2017 65:261–270

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Im o. g. CME-Beitrag wurden leider zwei Literaturangaben falsch zitiert, die Artikel sind hier mit der korrekten Autorenschaft nochmals …

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Speckled lentiginous nevus: understanding the process of development and regression

Speckled lentiginous nevus (SLN) is characterized by a brownish macule studded with blackish, multiple melanocytic nevi, although the cutaneous manifestations may vary by cases, and change by age. Therefore, there has been disagreement as to whether SLN is a congenital or acquired disease 1, 2). In rare cases of SLN, halo phenomenon may occur around the pre-existing lesion, associated with the coexistence of distant vitiligo 3). Here, we report a patient whose café-au-lait spot at birth changed to SLN, followed by the occurrence of vitiligo and poliosis through the process of spontaneous regression phenomenon against the SLN. We examined T-cell clones infiltrating around the melanocytic nevi and in the patient's peripheral blood.

This article is protected by copyright. All rights reserved.

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Correlations between pediatric obstructive sleep apnea and longitudinal growth

Publication date: Available online 8 January 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Do-Yang Park, Ji Ho Choi, So Young Kang, Jinjoo Han, Hun Yi Park, Jin Soon Hwang, Jae Ho Cho, Min Hyuk Cho, Hyun Jun Kim
ObjectivesPediatric obstructive sleep apnea has a relatively high prevalence and has various negative health and behavioral consequences. Among the various complications of pediatric obstructive sleep apnea, growth disturbance is still controversial.Method745 pediatric subjects with obstructive sleep apnea diagnosed by in-lab polysomnography were enrolled, after excluding ineligible subjects with abnormal growth related factors. Height, weight, and BMI of enrolled patients were measured and statistically converted to z-scores, and the converted data were analyzed statistically with the polysomnographic results. Multiple linear regression were used to analyze the relationships between age, gender, z-score for weight, polysomnography results, and z-score for height.ResultsPatients with higher respiratory related index or lower mean/lowest oxygen saturation of PSG showed smaller z-score for height. Mean apnea hypopnea index and standard deviation of enrolled patients was 7.46 ± 12.92, with moderate severity. And mean z-score for height and standard deviation was 0.21 ± 1.15. Apnea hypopnea index, respiratory disturbance index, obstructive apnea index, and hypopnea index, respiratory related results of polysomnography, were statistically negative correlated with a z-score for height. And mean oxygen saturation and lowest oxygen saturation, oxygen saturation results of polysomnography, were statistically positive correlated with a z-score for height.ConclusionsRespiratory related results and oxygen saturation results of polysomnography show negative and positive correlation with z-score for height. Therefore, pediatric obstructive sleep apnea have a negative effect on longitudinal growth.



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iPhone otoscopes: Currently available, but reliable for tele-otoscopy in the hands of parents?

Publication date: Available online 8 January 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Manan Udayan Shah, Maheep Sohal, Tulio A. Valdez, Christopher Grindle
ObjectivesTele-otoscopy has been validated for tympanostomy surveillance and remote diagnosis when images are recorded by trained professionals. The CellScope iPhone Otoscope is a device that may be used for tele-otoscopy and it enables parents to record their children's ear examinations and send the films for remote physician diagnosis. This study aims to determine the ability to diagnose, and the reliability of the diagnosis when utilizing video exams obtained by a parent versus video exams obtained by an otolaryngologist.MethodsParents of children ages 17 years or younger attempted recordings of the tympanic membrane of their children with the CellScope after a video tutorial; a physician subsequently used the device to record the same ear. Recordings occurred prior to standard pediatric otolaryngology office evaluation. Later, a remote pediatric otolaryngologist attempted diagnosis solely based on the videos, blinded to whether the examination was filmed by a parent or physician. Interrater reliability between video diagnosis and original diagnosis on pneumatic otoscopy was measured, and objective tympanic membrane landmarks visualized on the films were recorded.ResultsEighty ears were enrolled and recorded. There was low interrater agreement (k = 0.42) between diagnosis based on parent videos as compared with pneumatic otoscopy. There was high agreement (k = 0.71) between diagnosis based on physician videos and pneumatic otoscopy. Physician videos and parent videos had only slight agreement on objective landmarks identified (k = 0.087).ConclusionsiPhone otoscopy provides reliable tele-otoscopy images in when used by trained professionals but, currently, images obtained by parents are not suitable for use in diagnosis.



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Measuring Rheological Properties of Cement Pastes: Most common Techniques, Procedures and Challenges

http://ift.tt/2mcE06n

Turkey-KRG energy relations : internal and external dynamics

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Formation and reactivation of the Tien Shan constrained by multi-method basement and detrital chronology

http://ift.tt/2maxTzh

Structure-function relations of palm sap sugar in dark chocolate

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It's all part of the masterplan : pseudorabies virus passage across the basement membrane and modulation of plasmacytoid dendritic cell activation

http://ift.tt/2maQdrX

Balearic lime burials : new insights on an old funerary ritual

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Sanskrit reciprocal pronouns : their semantics and use in the Epics and Arthaśāstra (Is there any opposition between anyonyam and parasparam?)

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Determinants of Ankara-Brussels energy cooperation

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Cyprus Conflict Prevents EU-NATO Strategic Partnership

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Cyprus conflict as an obstacle to the EU-NATO strategic partnership

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Wavelet-Bayesian inference of cosmic strings embedded in the cosmic microwave background

McEwen, JD; Feeney, SM; Peiris, HV; Wiaux, Y; Ringeval, C; Bouchet, FR; (2017) Wavelet-Bayesian inference of cosmic strings embedded in the cosmic microwave background. Monthly Notices of the Royal Astronomical Society , 472 (4) pp. 4081-4098. 10.1093/mnras/stx2268 . Green open access

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The individual environment, not the family is the most important influence on preferences for common non-alcoholic beverages in adolescence

Smith, AD; Fildes, A; Forwood, S; Cooke, L; Llewellyn, C; (2017) The individual environment, not the family is the most important influence on preferences for common non-alcoholic beverages in adolescence. Scientific Reports , 7 , Article 16822. 10.1038/s41598-017-17020-x . Green open access

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TOOKAD (R) Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer

Azzouzi, AR; Barret, E; Bennet, J; Moore, C; Taneja, S; Muir, G; Villers, A; ... Emberton, M; + view all Azzouzi, AR; Barret, E; Bennet, J; Moore, C; Taneja, S; Muir, G; Villers, A; Coleman, J; Allen, C; Scherz, A; Emberton, M; - view fewer (2015) TOOKAD (R) Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer. World Journal of Urology , 33 (7) pp. 945-953. 10.1007/s00345-015-1505-8 . Green open access

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Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort

Blackburn, RM; Hayward, A; Cornes, M; McKee, M; Lewer, D; Whiteford, M; Menezes, D; ... Aldridge, RW; + view all Blackburn, RM; Hayward, A; Cornes, M; McKee, M; Lewer, D; Whiteford, M; Menezes, D; Luchenski, S; Story, A; Denaxas, S; Tinelli, M; Wurie, FB; Byng, R; Clark, MC; Fuller, J; Gabbay, M; Hewett, N; Kilmister, A; Manthorpe, J; Neale, J; Aldridge, RW; - view fewer (2017) Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort. BMJ Open , 7 (12) , Article e019282. 10.1136/bmjopen-2017-019282 . Green open access

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Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis

Leber, W; Beresford, L; Nightingale, C; Barbosa, EC; Morris, S; El-Shogri, F; McMullen, H; ... Griffiths, C; + view all Leber, W; Beresford, L; Nightingale, C; Barbosa, EC; Morris, S; El-Shogri, F; McMullen, H; Boomla, K; Delpech, V; Brown, A; Hutchinson, J; Apea, V; Symonds, M; Gilliham, S; Creighton, S; Shahmanesh, M; Fulop, N; Estcourt, C; Anderson, J; Figueroa, J; Griffiths, C; - view fewer (2017) Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis. BMJ Open , 7 (12) , Article e018163. 10.1136/bmjopen-2017-018163 . Green open access

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