Description of a novel RyR2 mutation in a juvenile patient with symptomatic catecholaminergic polymorphic ventricular tachycardia in sleep and during exercise: a case report

Catecholaminergic polymorphic ventricular tachycardia is an inherited disease presenting with arrhythmic events during physical exercise or emotional stress. If untreated, catecholaminergic polymorphic ventric...

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Association of benign paroxysmal positional vertigo with vitamin D deficiency: a systematic review and meta-analysis

Abstract

Background and objective

Benign paroxysmal positional vertigo (BPPV) is an idiopathic recurrent inner ear illness that is caused most often by an imbalance in the metabolism of calcium carbonate crystals (otoconia) inside the semicircular canals, in which the otoconia begin to circulate freely after being dislodged from the basic structure. The underlying etiology of this imbalance has not yet been well established; however, a few recent articles have revealed that vitamin D level abnormality in these patients might play a role. Therefore, we conducted the current systematic review analysis to explore potential associations of vitamin D level with the occurrence as well as the recurrence of BPPV disease.

Methods

A comprehensive literature search was conducted using different databases to retrieve all of the articles that have evaluated possible associations, irrespective of the study design. Then, we reported different vitamin D3 levels from BPPV groups and control groups to estimate the standardized mean difference (SMD) between the BPPV and control groups. We also calculated the effect size of each study under the random effects statistical model.

Results

Of the 703 studies that we identified, only 37 studies were found to be potential for our analysis, and of these, only seven met our predetermined criteria. Two meta-analyses were conducted with respect to the occurrence and the recurrence of BPPV. When the BPPV cases were compared to the controls (free of BPPV disease), there was an insignificant reduction in vitamin D level among the diseased groups (SMD = − 2.20; 95% CI − 6.66 to 2.26). In contrast, when the recurrent BPPV groups were compared with the non-recurrent BPPV groups, the statistical analysis showed significantly lower level of vitamin D among the recurrence BPPV groups (SMD = − 4.47; 95% CI − 7.55 to − 1.29).

Conclusion

Although a negative vitamin D imbalance has been reported among some BPPV patients, this review analysis failed to establish a relationship between the occurrence of BPPV and low vitamin D level. However, low vitamin D level was significantly evident among patients with recurrent episodes of BPPV.

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Investigation of ultra-low insertion speeds in an inelastic artificial cochlear model using custom-made cochlear implant electrodes

Abstract

Purpose

Latest research on cochlear implantations focuses on hearing preservation during insertion of the implant's electrode array by reducing insertion trauma. One parameter which may influence trauma is insertion speed. The objective of this study was to extend the range of examined insertion speeds to include ultra-low velocities, being lower than manually feasible, and investigate whether these reduce insertion forces.

Methods

24 custom-made cochlear implant test samples were fabricated and inserted into an artificial scala tympani model using 12 different insertion speeds while measuring the resulting insertion forces. Three commercially available slim straight electrode carriers were inserted using the same setup to analyze whether the results are comparable.

Results

Insertions of the test samples using high insertion speeds (2.0/2.8 mm/s) showed significantly higher insertion forces than insertions done with low insertion speeds (0.2 mm/s) or ultra-low insertion speeds (< 0.1 mm/s). The insertions with commercial slim straight electrode arrays showed significantly reduced insertion forces when using a low insertion speed as well.

Conclusions

Slow insertions showed significantly reduced insertion forces. Insertion speeds which are lower than manually feasible showed even lower insertion forces.

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Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and molecular analysis

Abstract

Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment. Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, β-catenin, and CK34βE12 was carried out on each neoplasm and on seven non-neoplastic urachal remnants as the control group. Additionally, a mutational analysis was performed using the QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised five females and two males with a mean age of 64 years. UrCs consisted of two mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas. Carcinoma antigen expression profile was positive for CK20 and negative for CK34βE12 and GATA3 in all cases. Five of seven cases stained positively for Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were immunoreactive for CK34βE12, CK7, and GATA3. Mutational analysis gave a positive result in four out of seven (57.1%) cases. All four positive tumors showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to the advanced stage at presentation, individualized treatment should be undertaken.

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Microsurgical Anatomy of Stapedius Muscle: Anatomy Revisited, Redefined with Potential Impact in Surgeries

Abstract

Stapedius muscle even though being the smallest skeletal muscle in human body, it has a major role in otology. As many of the distinguished books in otology missed to explain much about stapedius muscle, and also considering the need for the anatomy based visit to this small muscle we felt it was important to have a exercise like this. In the dissection hall of our institution we dissected 32 cadaveric temporal bones and delineated stapedius muscle as a part of PG teaching programme to have a clear idea of the anatomy of stapedius muscle, its origin, attachment, extension, size (all dimensions). Length of the stapedius muscle varied between 9 and 11 mm. Stapedial tendon measured about 2 mm. The muscle had a classical sickle shape with tendon looking like the handle of the sickle. It has a bulky belly with a maximum breadth of 2–3 mm. It was found to be medial to midportion of vertical limb of facial nerve. All of our temporal bones measured size varied from 9 to 11 mm in length excluding stapedial tendon. Stapedial tendon measured almost 2 mm. Muscle is classical sickle shaped with tendon acting like the handle of the sickle. It has a bulky tummy which forms the maximum breadth of 1–3 mm. Why to have a clear idea about the anatomy of stapedius muscle is that, unless the anatomy is clear there is chance of confusing the muscle with that of facial nerve while doing facial nerve grafting and also while drilling for facial nerve decompression in experienced hands may get confused and decompress the muscle. Stapedius muscle said to be the smallest muscle in the body, but its not as small as its been described. Detailed awareness of the anatomy of stapedius muscle is needed so as to avoid confusion while facial nerve grafting and while drilling.

https://ift.tt/2Cxz1I2

Microsurgical Anatomy of Stapedius Muscle: Anatomy Revisited, Redefined with Potential Impact in Surgeries

Abstract

Stapedius muscle even though being the smallest skeletal muscle in human body, it has a major role in otology. As many of the distinguished books in otology missed to explain much about stapedius muscle, and also considering the need for the anatomy based visit to this small muscle we felt it was important to have a exercise like this. In the dissection hall of our institution we dissected 32 cadaveric temporal bones and delineated stapedius muscle as a part of PG teaching programme to have a clear idea of the anatomy of stapedius muscle, its origin, attachment, extension, size (all dimensions). Length of the stapedius muscle varied between 9 and 11 mm. Stapedial tendon measured about 2 mm. The muscle had a classical sickle shape with tendon looking like the handle of the sickle. It has a bulky belly with a maximum breadth of 2–3 mm. It was found to be medial to midportion of vertical limb of facial nerve. All of our temporal bones measured size varied from 9 to 11 mm in length excluding stapedial tendon. Stapedial tendon measured almost 2 mm. Muscle is classical sickle shaped with tendon acting like the handle of the sickle. It has a bulky tummy which forms the maximum breadth of 1–3 mm. Why to have a clear idea about the anatomy of stapedius muscle is that, unless the anatomy is clear there is chance of confusing the muscle with that of facial nerve while doing facial nerve grafting and also while drilling for facial nerve decompression in experienced hands may get confused and decompress the muscle. Stapedius muscle said to be the smallest muscle in the body, but its not as small as its been described. Detailed awareness of the anatomy of stapedius muscle is needed so as to avoid confusion while facial nerve grafting and while drilling.

https://ift.tt/2Cxz1I2

Gender-Related Facial Surgical Goals

Facial plast Surg 2018; 34: 474-479
DOI: 10.1055/s-0038-1670648

In the last several years, there has been an increasing demand for surgical facial feminization or masculinization to treat the gender dysphoric patient. However, while aesthetic ideals for facial rejuvenation are well described and taught, there is a relative paucity of literature on how to achieve a feminine or masculine morphology. It is thus becoming increasingly important for facial plastic surgeons to understand patient goals regarding facial feminization or masculinization, and to have a systematic approach for analyzing the female and male face.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Achieving Ideal Facial Appearance

Facial plast Surg 2018; 34: 431-432
DOI: 10.1055/s-0038-1668573

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Enhanced Contouring of Local Flaps

Facial plast Surg 2018; 34: 433-442
DOI: 10.1055/s-0038-1668572

Scars and flaps represent a disruption of the normal skin contour, shape, and texture. Successful reconstruction of facial defects with local flaps requires prior planning to choose the correct reconstructive method. However, thorough preoperative planning should include consideration of adjunctive procedures to improve expected postoperative results as well as potential procedures to improve less-than-ideal results. Approaching facial reconstruction holistically allows the surgeon to soberly assess his/her reconstructive results and attain outstanding appearance.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Correction of the Crooked Nose

Facial plast Surg 2018; 34: 488-496
DOI: 10.1055/s-0038-1672142

Successful management of the crooked nose can be a formidable task and requires a systematic approach that begins with an understanding of the patients' aesthetic desires, expectations, and functional symptoms. Dividing the nose into thirds and organizing a plan to correct each region individually can simplify the preoperative planning. There are two broad philosophical strategies of surgical management: engineering (reconstructive) and artistic (camouflaging). While the camouflaging technique is helpful for minor asymmetries, protrusions, and depressions, the engineering approach is best for more extreme corrections. The surgeon must be skilled in both approaches as either one or a combination of the two may yield the best results. Once corrected, postoperative care is essential to obtain optimal outcomes.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Widened Dorsum: Bony and Cartilaginous Contributions

Facial plast Surg 2018; 34: 443-447
DOI: 10.1055/s-0038-1669989

Creation of a pleasing dorsal nasal profile in the anterior and lateral views requires proper analysis and planning to determine the required series of steps to accomplish the desired outcome. The widened nasal dorsum is a common esthetic complaint of the patient seeking rhinoplasty. Often patients seek an unrealistic result that, if accomplished, would leave them with a restricted nasal vault and nasal airway compromise. Nasal function must be balanced with the patient and surgeon's desire to narrow the nasal dorsum. Various techniques are used to control the width of the upper third, or bony vault, and middle third, or cartilaginous vault.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Surgical and Nonsurgical Techniques in Forehead Rejuvenation

Facial plast Surg 2018; 34: 466-473
DOI: 10.1055/s-0038-1669990

The periorbital and forehead regions are among the most expressive parts of the face. A thorough understanding of the complex facial anatomy and aesthetic norms are essential when evaluating and treating a patient for facial brow rejuvenation. Not only will knowledge of the anatomy enhance facial injection and surgical outcomes, but will also diminish potential complications. Combining nonsurgical and surgical techniques, including laser and skin rejuvenation, can yield the most natural and effective aesthetic brow improvements.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Facial Scar Improvement Procedures

Facial plast Surg 2018; 34: 448-457
DOI: 10.1055/s-0038-1669400

Scars are a natural part of dermal healing following lacerations, incisions, or tissue loss. The ideal scar is narrow, flat, level with surrounding tissue, and difficult for the untrained eye to see due to color match and placement parallel to relaxed skin tension lines; however, scarring that is dyspigmented, hypertrophied, widened, contracted, or atrophic can be aesthetically displeasing or causing functional limitations. When the scar has unfavorable characteristics, scar revision is often indicated and the cosmetic surgeon must be knowledgeable of the minimally invasive as well as surgical techniques to improve aesthetics, reduced reoccurrence, or correct functional limitations.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Correction of the Lower Face and Neck

Facial plast Surg 2018; 34: 480-487
DOI: 10.1055/s-0038-1672128

Rejuvenation of the lower face and neck strives to reverse signs of aging while optimizing the patient's natural anatomy. Common features of an aesthetically pleasing lower face include a well-defined and appropriately balanced mandible and an acute cervicomental angle. Correction of the aging lower face and neck is accomplished through multiple surgical interventions, performed either alone or in combination. Determination of appropriate procedures is based on individual anatomic pathology. Intimate knowledge of facial anatomy and the complexity of the aging process is paramount to achieve a natural and aesthetic result. Thorough patient evaluation and counseling should precede any intervention. Specifically, the surgeon should be cognizant of the patient's skeletal structure, soft tissue distribution, muscular anatomy, and skin quality. Appropriate postoperative care and management of complications are vital to success.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Ideal Facial Relationships and Goals

Facial plast Surg 2018; 34: 458-465
DOI: 10.1055/s-0038-1669401

Analysis of the face is an essential component of facial plastic surgery. In training, we are taught standards and ideals based on neoclassical models of beauty from Greek and Roman art and architecture. In practice, we encounter a wide range of variation in patient desires and perceptions of beauty. Our goals seem to be ever shifting, yet our education has provided us with a foundation from which to draw ideals of beauty. Plastic surgeons must synthesize classical ideas of beauty with patient desires, cultural nuances, and ethnic considerations all the while maintaining a natural appearance and result. This article gives an overview of classical models of facial proportions and relationships, while also discussing unique ethnic and cultural considerations which may influence the goal for the individual patient.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Selecting the Best Eyelid Techniques

Facial plast Surg 2018; 34: 497-504
DOI: 10.1055/s-0038-1672148

The periorbital region is a focal point on the face. Dermatochalasis, fat herniation, blepharoptosis, brow ptosis, deep tear troughs, and malar fat pad descent are all age-related changes that occur around the eyes, and successful rejuvenation involves addressing all of these changes. Restoring a youthful, vibrant appearance to the eyes and periorbital areas can often only be accomplished with a combination of surgical and nonsurgical interventions. Facial plastic surgeons should have a comprehensive knowledge of all of these options and their applications to ensure good patient outcomes and satisfaction.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Rejuvenation of the Midface

Facial plast Surg 2018; 34: 505-523
DOI: 10.1055/s-0038-1672161

In this article, the interested reader will learn when and how to apply different techniques on their patients, with the goal of safe, effective, natural looking, and long-lasting midface rejuvenation.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Drug repurposing for Leishmania. Molecular basis of the leishmanicidal activity of the antidepressant sertraline. [Mechanisms of Action]

Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress in L. infantum promastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as shortage of intracellular amino acids used as metabolic fuel by Leishmania. Sertraline killed Leishmania through a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy.

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Role of capsule in resistance to disinfectants, host antimicrobials and desiccation in Acinetobacter baumannii [Mechanisms of Resistance]

Acinetobacter baumannii strain AB5075 forms two cell types distinguished by their opaque (VIR-O) or translucent (AV-T) colonies. VIR-O cells possess a thicker capsule and are more resistant to a variety of stressors. However, the direct role of capsule in these stressors was unknown. This study demonstrates that capsule is required for resistance to disinfectants, lysozyme and desiccation in Acinetobacter baumannii. In addition, capsule is required for survival in a mouse lung model of infection.

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Effects of Food and Omeprazole on Novel Formulation SUBA-Itraconazole in Healthy Subjects [Pharmacology]

To address the limited bioavailability and intolerance of the conventional itraconazole formulations, a new formulation labelled SUBA-itraconazole (for SUper BioAvailability) has been developed, however the specific effect of food and gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA-itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. The effect of food was assessed in an open-label, randomized, cross-over bioavailability study of SUBA-itraconazole capsules 65 mg (2 x 65 mg BID) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Secondly, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n=28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA-itraconazole capsules (2 x 65 mg/day) with and without co-administration of daily omeprazole delayed-release capsules (1 x 40 mg/day) under steady-state conditions. In the fed and fasted state SUBA-itraconazole demonstrated similar concentrations at the end of the dosing interval, with modestly lower total and peak itraconazole (ITZ) exposure when administered under fed conditions compared to the fasted state; fed/fasted ratios of 78.09% (90%CI 74.49-81.86%) for AUC_tau [14183.2 vs. 18479.8 hr·ng/mL], 73.05% (90%CI 69.01-77.33%) for C_max,ss [1519.1 vs. 2085.2 ng/mL] and 91.53% (90%CI 86.41-96.96%) for C_trough [1071.5 vs. 1218.5 ng/mL]. When dosed concomitantly with omeprazole there was a 22% increase in total plasma exposure of ITZ, as measured by AUC_0- (p = 0.0069), and a 31% increase in peak plasma exposure of ITZ, as measured by C_max (p = 0.0083).

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Amixicile reduces severity of cryptosporidiosis, but does not have in vitro activity against Cryptosporidium [Mechanisms of Action]

Cryptosporidium causes significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here we show that amixicile, a highly selective water soluble derivative of NTZ diminishes Cryptosporidium severity in a malnourished mouse model despite a lack of direct anti-cryptosporidial activity. We suggest that amixicile; by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology.

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Breaking the vicious cycle of antibiotic killing and regrowth of biofilm-residing Pseudomonas aeruginosa [Pharmacology]

Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physico-chemical insults. In addition to the general recalcitrance of biofilm-bacteria, high bacterial loads in biofilm-associated infections significantly diminishes the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols, that have been established to serve the eradication of acute infections, fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy on Pseudomonas aeruginosa to monitor dynamic killing of biofilm-grown bacteria by tobramycin and colistin in real-time. We revealed that the time required for surviving bacteria to repopulate the biofilm could be taken as measure for effectiveness of the antimicrobial treatment. It depends on the: i) nature and concentration of the antibiotic, ii) duration of antibiotic treatment; iii) application as mono or combination therapy and iv) time intervals of drug administration. The vicious cycle of killing and repopulation of biofilm bacteria could also be broken in an in vivo model system by applying successive antibiotic dosages with time intervals that do not allow full reconstitution of the biofilm communities. Treatment regimens that consider the important aspects of antimicrobial killing kinetics bear the potential to improve control of biofilm regrowth. This is an important and underestimated factor that is bound to ensure sustainable treatment success of chronic infections.

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Two regulators, PA3898 and PA2100, modulate the Pseudomonas aeruginosa multidrug resistance MexAB-OprM and EmrAB efflux-pumps and biofilm formation [Mechanisms of Resistance]

It is generally believed that the Pseudomonas aeruginosa biofilm matrix itself acts as a molecular sieve or sink that contributes to significant levels of drug resistance, but it is becoming more apparent that multidrug efflux-pumps induced during biofilm growth significantly enhances resistance levels. We present here a novel transcriptional regulator, PA3898, which controls biofilm formation and multidrug efflux-pumps in P. aeruginosa. A mutant of this regulator significantly reduced the ability of P. aeruginosa to produce biofilm in vitro, and affected its in vivo fitness and pathogenesis in Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA3898 modulates essential virulence genes/pathways, including multidrug efflux-pumps and phenazine biosynthesis. ChIP-seq identified its DNA binding sequences and confirmed PA3898 directly interacts with promoter regions of four genes/operons, two of which are mexAB-oprM and phz2. Co-immunoprecipitation revealed a regulatory partner of PA3898 as PA2100, and both are required for binding to DNA in electrophoresis mobility shift assays. PA3898 and PA2100 were given the names MdrR1 and MdrR2, respectively, as novel repressors of the mexAB-oprM multidrug efflux operon and activators for another multidrug efflux pump EmrAB. Interaction between MdrR1 and MdrR2 to the promoter regions of their regulons was further characterized via localized surface plasmon resonance and DNA footprinting. These regulators directly repress the mexAB-oprM operon, independent of its well-established MexR regulator. Mutants of mdrR1 and mdrR2 caused increased resistance to multiple antibiotics in P. aeruginosa, validating the significance of these newly discovered regulators.

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Polymorphism of polymeric amino acid regions in fungal proteins: correlation with altered echinocandin and azole susceptibility [Mechanisms of Resistance]

Polymorphism of polymeric amino acid (polyX) regions within fungal proteins represents a potential mechanism for rapid genotypic adaptation to environmental pressures including antifungal exposure. PolyQ was the most abundant repeat in the proteomes of 8 diverse fungal species, and was preferentially found in regulatory proteins. In Candida glabrata, polyX polymorphisms were characterized in 36 proteins implicated in azole or echinocandin susceptibility. General transcriptional repressor Tup1A exhibited Q44/Q45 polymorphism, and Hog1 signalling component Ssk2 exhibited N44/N45, in phylogenetically matched echinocandin and azole, respectively, susceptible/resistant strains.

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Competitive fitness of essential gene knockdowns reveals a broad-spectrum antibacterial inhibitor of the cell division protein FtsZ [Mechanisms of Action]

To streamline elucidation of antibacterial compounds' mechanism of action, comprehensive high-throughput assays interrogating multiple putative targets are necessary. However, current chemogenomic approaches for antibiotic target identification have not fully utilized the multiplexing potential of next-generation sequencing. Here, we used Illumina sequencing of transposon insertions to track the competitive fitness of a Burkholderia cenocepacia library containing essential gene knockdowns. Using this method, we characterized a novel benzothiadiazole derivative, 10126109 (C109) with antibacterial activity against B. cenocepacia, for which whole-genome sequencing of low-frequency, spontaneous drug-resistant mutants had failed to identify the drug target. By combining identification of hypersusceptible mutants and morphology screening, we show that C109 targets cell division. Furthermore, fluorescence microscopy of bacteria harboring GFP-cell division protein fusions revealed that C109 prevents divisome formation by altering the localization of the essential cell division protein FtsZ. In agreement with this, C109 inhibited both the GTPase and polymerization activities of purified B. cenocepacia FtsZ. C109 displayed antibacterial activity against Gram-positive and Gram-negative cystic fibrosis pathogens, including Mycobacterium abscessus. C109 effectively cleared B. cenocepacia infection in the Caenorhabditis elegans model and exhibited additive interactions with clinically relevant antibiotics. Hence, C109 is an enticing candidate for further drug development.

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Lipase precursor like protein promotes miltefosine tolerance in Leishmania donovani by enhancing parasite infectivity and eliciting anti-inflammatory responses in host macrophages [Mechanisms of Resistance]

Oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the year 2002 for the treatment of visceral leishmaniasis (VL). However, recent reports on its declining efficacy and increasing relapse rates pose a serious concern. An understanding of the factors contributing to MIL tolerance in Leishmania parasites is critical. In the present study, we assessed the role of lipase precursor like protein (Lip) in conferring tolerance towards miltefosine by episomally overexpressing Lip into L. donovani (LdLip⁺⁺). We observed significant increase (~3 fold) in MIL IC₅₀ both at promastigote (3.90 ± 0.68 µM, P<0.05) and at intracellular amastigote (9.10 ± 0.60 µM, P<0.05) stages compared to the wild type counterpart (LdNeo; MIL IC₅₀ promastigote 1.49 ± 0.20 µM; MIL IC₅₀ amastigote 3.95 ± 0.45 µM). LdLip⁺⁺ parasites exhibited significantly (P<0.05) increased infectivity to host macrophages, increased metacyclogenesis and tolerance to MIL induced oxidative stress. The susceptibility of LdLip⁺⁺ towards other antileishmanial drugs (sodium antimony gluconate and amphotericin B) remained unchanged. In comparison to LdNeo, the LdLip⁺⁺ parasites elicited higher host IL-10 cytokine expression (1.6 fold, P<0.05) with reduced expression of TNF-α cytokine (1.5 fold, P<0.05), leading to significantly (P<0.01) increased ratio of IL-10/TNF- α. The above findings suggest a role of lipase precursor like protein in conferring tolerance towards oral antileishmanial drug MIL in L. donovani parasites.

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Button Battery Safety

The pediatric button battery (BB) hazard has been recognized for several decades. In 2012, the National Button Battery Task Force was established, and most manufacturers have improved warning labels, more secure packaging, and made BB compartments in products are more secure. Tissue neutralization before BB removal (ie, honey or sucralfate/Carafate®) is an effective way to reduce the rate of BB injury. In absence of visible perforation, 0.25% sterile acetic acid esophageal tissue irrigation at time of BB removal is recommended as a neutralization strategy to mitigate injury progression. Future BB design changes could eliminate esophageal tissue injury.

https://ift.tt/2RBqpEs

Improved patient adherence to subcutaneous allergen immunotherapy using a modified rush immunotherapy protocol

Despite the efficacy of allergen immunotherapy (AIT), studies demonstrate low compliance rates.1 Adherence during build-up is especially challenging for patients. Rush immunotherapy (RIT) provides a faster method to reach maintenance dose, eliminating several months of build-up, potentially leading to higher patient adherence and accelerated symptom control. Few studies have directly compared the compliance rates of RIT schedules vs conventional schedules in patients from the same office.2 Safety and increased frequency of reaction rate continue to be primary concerns of RIT.

https://ift.tt/2OdKPoL

Anaphylaxis After Anal Intercourse With Tolerance By Vaginal Route

Anaphylaxis induced by coitus is an uncommon phenomenon 1, 2. The true prevalence is unknown, but it is believed to affect up to 40,000 women in the United States 3. The clinical features may vary in severity from mild immediate reactions as vaginal itching after coitus to systemic reactions such as systemic urticaria or even anaphylactic shock 1. The main agent involved in the few reported cases is seminal fluid, although cases of hypersensitivity to other agents such as latex, spermicidal agents, foods, drugs or lubricants have been reported.

https://ift.tt/2QCzOtT

Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT

The clinical benefit of allergen-specific immunotherapy (AIT) involves induction of blocking antibodies. It is not clear if these antibodies function via steric hindrance alone or a combination of levels, avid...

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CPAP-Nutzungsprobleme und Zweitlinientherapie bei obstruktiver Schlafapnoe

https://ift.tt/2E38Vho

Diagnosen von Schilddrüsenerkrankungen in HNO-Praxen und Hausarztpraxen in Deutschland 2008–2016

Zusammenfassung

Zielsetzung

Das Ziel dieser Studie war die Untersuchung von Diagnosen von Schilddrüsenerkrankungen aus deutschen HNO-Praxen im Vergleich zu Hausarztpraxen mithilfe von Daten aus einer repräsentativen deutschlandweiten Praxisdatenbank.

Methode

Die Datenbank wurde retrospektiv nach Diagnosen von Schilddrüsenerkrankungen aus HNO-Praxen und Hausarztpraxen zwischen Januar 2008 und Dezember 2016 durchsucht. Erhoben wurden die häufigsten dreistelligen Krankheitsklassen (Kategorien) aus der Gruppe „Krankheiten der Schilddrüse" (E00–E07) sowie die Kategorien „Gutartige Neubildung der Schilddrüse" (D34) und „Bösartige Neubildung der Schilddrüse" (C73). Ausgewertet wurden die Zeiträume 2008–2010, 2011–2013 sowie 2014–2016.

Ergebnisse

Die Datenbank enthielt 71 HNO-Praxen und 506 Hausarztpraxen mit kontinuierlicher Mitarbeit von 2008–2016. Die relative Häufigkeit (Patienten pro Praxis) von Diagnosen aus der Gruppe „Erkrankungen der Schilddrüse" war in Hausarztpraxen 4,4-mal höher als in HNO-Praxen. Die relative Häufigkeit von gutartigen Neubildungen der Schilddrüse war in Hausarztpraxen 5‑mal höher als in HNO-Praxen. Die relative Häufigkeit von bösartigen Neubildungen der Schilddrüse war in Hausarztpraxen und HNO-Praxen in etwa gleich hoch. Die häufigsten Diagnosen stammten sowohl in HNO-Praxen als auch in Hausarztpraxen aus den Kategorien „Sonstige nichttoxische Struma" (E04) und „Sonstige Hypothyreose" (E03). Weniger häufig waren Diagnosen aus den Kategorien „Hyperthyreose" (E05) und „Thyreoiditis" (E06). Die geringste Häufigkeit wiesen Diagnosen von Neubildungen der Schilddrüse auf, wobei in Hausarztpraxen Diagnosen von gutartigen Neubildungen, in HNO-Praxen hingegen Diagnosen von bösartigen Neubildungen der Schilddrüse überwogen. Im Verlauf des Studienzeitraums nahm die Diagnosehäufigkeit von Schilddrüsenerkrankungen in HNO-Praxen ab, wohingegen sie in Hausarztpraxen zunahm.

Schlussfolgerung

Trotz des in den letzten Jahren in Deutschland deutlich zunehmenden Interesses an der Etablierung der Schilddrüsenchirurgie in HNO-Kliniken zeigt sich ein kontinuierlicher Rückgang von Schilddrüsendiagnosen in deutschen HNO-Praxen bei gleichzeitiger deutlicher Zunahme in Hausarztpraxen. Ursächlich hierfür könnten kassenärztliche Vergütungsunterschiede zwischen hausärztlicher und fachärztlicher Tätigkeit sein.

https://ift.tt/2RCHCxp

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

Abstract

Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.

https://ift.tt/2INxCgI

Developmental origin and sex-specific risk for infections and immune diseases later in life

Abstract

The intrauterine environment is an important determinant of immunity later in life of the offspring. An altered prenatal immune development can result in a high postnatal risk for infections, chronic immune diseases, and autoimmunity. Many of these immune diseases show a strong sex bias, such as a high incidence of autoimmune diseases and allergies in adult females or a high risk for infections in males. Here, we comprehensively review established pathways and propose novel concepts modulating the risk for such poor immunity during childhood and throughout life. Moreover, we highlight how an adverse fetal environment may affect or aggravate the risk for poor immunity in a sex-specific manner. An improved understanding of a sex-specific susceptibility to poor immunity along with insights on how such risk can be modulated before or around birth will allow the development of tailored prevention strategies.

https://ift.tt/2CwaW41

Sex and sex steroids impact influenza pathogenesis across the life course

Abstract

Males and females differ in the outcome of influenza A virus (IAV) infections, which depends significantly on age. During a typical seasonal influenza epidemic, young children (< 10 years of age) and aged adults (65+ years of age) are at greatest risk for severe disease, and among these age groups, males tend to suffer a worse outcome from IAV infection than females. Following infection with either pandemic or outbreak strains of IAVs, females of reproductive ages (i.e., 15–49 years of age) experience a worse outcome than their male counterparts. Among females of reproductive ages, pregnancy is one factor linked to an increased risk of severe outcome of influenza, although it is not the sole factor explaining the female-preponderance of severe disease. Small animal models of influenza virus infection illustrate that inflammatory immune responses and repair of damaged tissue following IAV infection also differ between the sexes and impact the outcome of infection. There also is growing evidence that sex steroid hormones, including estrogens, progesterone, and testosterone, directly impact immune responses during IAV infection to alter outcomes. Greater consideration of the combined effects of sex and age as biological variables in epidemiological, clinical, and animal studies of influenza pathogenesis is needed.

https://ift.tt/2IJJboX

Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease with vascular malformations in several systems of the body, most commonly the skin and gastrointestinal tract. Bleeding from the gastrointestinal (GI) tract is a major complication, which may lead to chronic iron deficiency anemia and the need for frequent blood transfusions due to ongoing gastrointestinal blood loss. In this case report, we describe a now 19-year-old female with BRBNS who required six blood transfusions per year and after starting sirolimus is symptom- and transfusion-free.

https://ift.tt/2NsL2zr

Serum miRNA-371b-5p and miRNA-5100 act as biomarkers for systemic lupus erythematosus

Publication date: Available online 7 October 2018

Source: Clinical Immunology

Author(s): Li Zeng, Jia-li Wu, Li-min Liu, Ju-qing Jiang, Hai-jing Wu, Ming Zhao, Qian-jin Lu

Abstract

MicroRNAs (miRNAs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here, we investigated the serum miRNAs expression profiles in the serum of SLE and healthy controls, and identified the potential serum biomarkers for SLE. We screened and identified the differentially expressed miRNAs such as miR-371b-5p, miR-5100, miR-146a-5p among active SLE, inactive SLE and healthy controls based on the miRNAs expression array. Furthermore, the results of RT-qPCR confirmed that miR-371b-5p and miR-5100 expression was different among active SLE, inactive SLE and healthy controls. Moreover, we performed in a large cohort which we validated that expression of miR-371b-5p and miR-5100 was increased significantly in the serum of SLE compared with healthy controls and rheumatoid arthritis (RA), and was also higher in active SLE than that in inactive SLE. In addition, we found the associations between the expression levels of miR-371b-5p and miR-5100 and these clinical parameters of SLE. These results suggested that miR-371b-5p and miR-5100 may act as serum biomarkers for SLE.

https://ift.tt/2ynkutQ

Early (90‐day) mortality after radical radiotherapy for head and neck squamous cell carcinoma: A population‐based analysis

Head &Neck, EarlyView.


https://ift.tt/2ylhUof

Effective connectivity inferred from fMRI transition dynamics during movie viewing points to a balanced reconfiguration of cortical interactions

Gilson, M; Deco, G; Friston, KJ; Hagmann, P; Mantini, D; Betti, V; Romani, GL; Gilson, M; Deco, G; Friston, KJ; Hagmann, P; Mantini, D; Betti, V; Romani, GL; Corbetta, M; - view fewer (2018) Effective connectivity inferred from fMRI transition dynamics during movie viewing points to a balanced reconfiguration of cortical interactions. NeuroImage , 180 pp. 534-546. 10.1016/j.neuroimage.2017.09.061 .

https://ift.tt/2pImRDJ

The impact of Western criticisms of Japanese rhetorical approaches on learners of Japanese

McKinley, J; (2014) The impact of Western criticisms of Japanese rhetorical approaches on learners of Japanese. Language Learning in Higher Education , 4 (2) pp. 303-319. 10.1515/cercles-2014-0017 . Green open access

https://ift.tt/2yqVwcS

Controlled Arrangement of Neuronal Cells on Surfaces Functionalized with Micropatterned Polymer Brushes

Pardo-Figuerez, M; Martin, NRW; Player, DJ; Roach, P; Christie, SDR; Capel, AJ; Lewis, MP; (2018) Controlled Arrangement of Neuronal Cells on Surfaces Functionalized with Micropatterned Polymer Brushes. ACS Omega 10.1021/acsomega.8b01698 . (In press). Green open access

https://ift.tt/2pIFpU0

Limits on the Contribution of Endogenic Radiolysis to the Presence of Molecular Oxygen in Comet 67P/Churyumov-Gerasimenko

Bouquet, A; Mousis, O; Teolis, B; Nicolaou, G; Ozgurel, O; Pauzat, F; Ellinger, Y; ... Waite, JH; + view all Bouquet, A; Mousis, O; Teolis, B; Nicolaou, G; Ozgurel, O; Pauzat, F; Ellinger, Y; Ronnet, T; Waite, JH; - view fewer (2018) Limits on the Contribution of Endogenic Radiolysis to the Presence of Molecular Oxygen in Comet 67P/Churyumov-Gerasimenko. Astrophysical Journal , 864 (1) 10.3847/1538-4357/aad22f . Green open access

https://ift.tt/2ylcF83

Clinical Applications of Stochastic Dynamic Models of the Brain, Part I: A Primer

Roberts, JA; Friston, KJ; Breakspear, M; (2017) Clinical Applications of Stochastic Dynamic Models of the Brain, Part I: A Primer. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging , 2 (3) pp. 216-224. 10.1016/j.bpsc.2017.01.010 . Green open access

https://ift.tt/2pGzcIr

Maternal Stress and the Functions of Positivity in Mothers of Children with Intellectual Disability

Jess, M; Totsika, V; Hastings, RP; (2018) Maternal Stress and the Functions of Positivity in Mothers of Children with Intellectual Disability. Journal of Child and Family Studies , 27 (11) pp. 3753-3763. 10.1007/s10826-018-1186-1 . Green open access

https://ift.tt/2ynyQKH

A mathematical model of embodied consciousness

Rudrauf, D; Bennequin, D; Granic, I; Landini, G; Friston, K; Williford, K; (2017) A mathematical model of embodied consciousness. Journal of Theoretical Biology , 428 pp. 106-131. 10.1016/j.jtbi.2017.05.032 . Green open access

https://ift.tt/2pIl8hK

Google search patterns monitoring the daily health impact of heatwaves in England: How do the findings compare to established syndromic surveillance systems from 2013 to 2017?

Green, HK; Edeghere, O; Elliot, AJ; Cox, IJ; Morbey, R; Pebody, R; Bone, A; ... Smith, GE; + view all Green, HK; Edeghere, O; Elliot, AJ; Cox, IJ; Morbey, R; Pebody, R; Bone, A; McKendry, RA; Smith, GE; - view fewer (2018) Google search patterns monitoring the daily health impact of heatwaves in England: How do the findings compare to established syndromic surveillance systems from 2013 to 2017? Environmental Research , 166 pp. 707-712. 10.1016/j.envres.2018.04.002 .

https://ift.tt/2ym2cJn

Parents’ perceptions of outcomes of orthodontic treatment in adolescent patients: a qualitative study

Shah, R; Alquraini, N; Cunningham, SJ; (2019) Parents' perceptions of outcomes of orthodontic treatment in adolescent patients: a qualitative study. European Journal of Orthodontics (In press).

https://ift.tt/2pIEXoM

Clinical Applications of Stochastic Dynamic Models of the Brain, Part II: A Review

Roberts, JA; Friston, KJ; Breakspear, M; (2017) Clinical Applications of Stochastic Dynamic Models of the Brain, Part II: A Review. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging , 2 (3) pp. 225-234. 10.1016/j.bpsc.2016.12.009 . Green open access

https://ift.tt/2yiEiOM

On the importance of modeling fMRI transients when estimating effective connectivity: A dynamic causal modeling study using ASL data

Havlicek, M; Roebroeck, A; Friston, KJ; Gardumi, A; Ivanov, D; Uludag, K; (2017) On the importance of modeling fMRI transients when estimating effective connectivity: A dynamic causal modeling study using ASL data. NeuroImage , 155 pp. 217-233. 10.1016/j.neuroimage.2017.03.017 . Green open access

https://ift.tt/2pFbbkZ

Embodiment and Schizophrenia: A Review of Implications and Applications

Tschacher, W; Giersch, A; Friston, K; (2017) Embodiment and Schizophrenia: A Review of Implications and Applications. Schizophrenia Bulletin , 43 (4) pp. 745-753. 10.1093/schbul/sbw220 . Green open access

https://ift.tt/2ykxujT

Chaperone-mediated autophagy as a therapeutic target for Parkinson disease

Campbell, P; Morris, H; Schapira, A; (2018) Chaperone-mediated autophagy as a therapeutic target for Parkinson disease. Expert Opinion on Therapeutic Targets , 22 (10) pp. 823-832. 10.1080/14728222.2018.1517156 .

https://ift.tt/2pIl7uc

A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography - case study

Pironti, E; Salpietro, V; Cucinotta, F; Granata, F; Mormina, E; Efthymiou, S; Scuderi, C; ... Di Rosa, G; + view all Pironti, E; Salpietro, V; Cucinotta, F; Granata, F; Mormina, E; Efthymiou, S; Scuderi, C; Gagliano, A; Houlden, H; Di Rosa, G; - view fewer (2018) A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography - case study. Journal of Neurogenetics 10.1080/01677063.2018.1476510 . (In press).

https://ift.tt/2ynUEWF

Local Structure and Polar Order in Liquid N-Methyl-2-pyrrolidone (NMP)

Basma, NS; Headen, TF; Shaffer, MSP; Skipper, NT; Howard, CA; (2018) Local Structure and Polar Order in Liquid N-Methyl-2-pyrrolidone (NMP). The Journal of Physical Chemistry B , 122 (38) pp. 8963-8971. 10.1021/acs.jpcb.8b08020 . Green open access

https://ift.tt/2pFaRmh

Die rolle des kohlenstoffs in der prähistorischen metallurgie

Rehren, T; (1997) Die rolle des kohlenstoffs in der prähistorischen metallurgie. Stahl und Eisen , 117 (9) pp. 87-92.

https://ift.tt/2ykxe4p

A concise patient reported outcome measure for people with aphasia: the aphasia impact questionnaire 21

Swinburn, K; Best, W; Beeke, S; Cruice, M; Smith, L; Pearce Willis, E; Ledingham, K; ... McVicker, SJ; + view all Swinburn, K; Best, W; Beeke, S; Cruice, M; Smith, L; Pearce Willis, E; Ledingham, K; Sweeney, J; McVicker, SJ; - view fewer (2018) A concise patient reported outcome measure for people with aphasia: the aphasia impact questionnaire 21. Aphasiology 10.1080/02687038.2018.1517406 . (In press).

https://ift.tt/2pHHcsx

Revealing silicon crystal defects by conductive atomic force microscope

Liu, X; Yu, B; Zou, Y; Zhou, C; Li, X; Wu, J; Liu, H; ... Qian, L; + view all Liu, X; Yu, B; Zou, Y; Zhou, C; Li, X; Wu, J; Liu, H; Chen, L; Qian, L; - view fewer (2018) Revealing silicon crystal defects by conductive atomic force microscope. Applied Physics Letters , 113 (10) , Article 101601. 10.1063/1.5044518 .

https://ift.tt/2yiE3mQ

A combined experimental and computational study on the reaction of fluoroarenes with Mg–Mg, Mg–Zn, Mg–Al and Al–Zn bonds

Bakewell, C; Ward, BJ; White, AJP; Crimmin, MR; (2018) A combined experimental and computational study on the reaction of fluoroarenes with Mg–Mg, Mg–Zn, Mg–Al and Al–Zn bonds. Chemical Science , 9 (8) pp. 2348-2356. 10.1039/C7SC05059C . Green open access

https://ift.tt/2pJzQoA

Topological phase transitions driven by strain in monolayer tellurium

Zhang, W; Wu, Q; Yazyev, O; Weng, H; Guo, Z; Cheng, W-D; Chai, G-L; (2018) Topological phase transitions driven by strain in monolayer tellurium. Physical Review B , 98 (11) , Article 115411. 10.1103/PhysRevB.98.115411 . Green open access

https://ift.tt/2ynmUZj

Massive retroperitoneal dedifferentiated liposarcoma in a young patient

Abstract

Liposarcomas are rare malignant tumors that mostly develop in the retroperitoneum. They have a broad behavioral spectrum, from small masses of tissue to highly aggressive tumors. The dedifferentiation process occurs in up to 10% and it's most likely to occur in the retroperitoneum, a process that not only changes its components but also its prognosis. These tumors can grow to a massive size since most of them do not give any symptoms until they invade the adjacent structures. Timely detection and surgery could avoid all these potentially lethal scenarios. We present a case of a 34-year-old patient, who reported a growing mass in her abdomen that reached massive proportions but remained untreated due to lack of sufficient access to healthcare facilities in her geographic location. After complete removal of the mass the patient underwent complete recovery, dedifferentiated liposarcoma was the final diagnosis.

https://ift.tt/2PmSUUL

Synchronous malignant phyllodes tumour and invasive lobular carcinoma—case report and review

Abstract

Synchronous phyllodes tumour and invasive lobular carcinoma is an extremely rare event. We report these concurrent diagnoses in a patient observed in an ipsilateral breast, suspected due to breast risk factors (family history and lobular carcinoma in situ) and the presence of malignant phyllodes. Screening breast magnetic resonance imaging was able to identify the carcinoma which was occult in other imaging. An understanding of the possibility of dual diagnoses may lead to additional investigations for its identification. Treatment may then be tailored to the individual's pathology.

https://ift.tt/2OJZHe6

Giant myxoid liposarcoma of the gluteal region: case report of patient caused delay of surgical treatment and review of the literature

Abstract

Although adult soft tissue sarcoma is a rare disease, it needs individual treatment by an experienced, interdisciplinary team. We present an exceptional case of a 36-year-old woman suffering from a giant intermediate grade myxoid liposarcoma of the left buttock. She had been seen 4 years earlier but refused to undergo any treatment by then. Now suffering from a foul, ulcerating and superinfected tumor she agreed to surgical treatment. Despite delay, treatment could be performed according to the most up to date sarcoma guidelines which are discussed, including a brief review of the literature.

https://ift.tt/2Pk1DXK

Spontaneous resolution of a spontaneous steinstrasse: a case report

Abstract

A 63-year-old man presented with a 4-day history of right sided loin-to-groin pain. Computed tomography imaging revealed a 22 mm by 7 mm volume of contiguous ureteric calculi at the right vesicoureteric junction. Spontaneous steinstrasse was diagnosed with no recent history of extracorporeal shock wave lithotripsy (ESWL) or other urological intervention to the right kidney. Metabolic testing was negative. An initial plan was made for urgent primary ureteroscopy and lithotripsy, however, the patient spontaneously passed 20–25 calculi at home whilst awaiting his operation date. He was reviewed in clinic and his symptoms had resolved. His ureteroscopy was cancelled. This case represents an example of spontaneous steinstrasse with no identified causative factors, a rare occurrence on which little literature is available presenting a management dilemma to the treating clinician. The case described resolved prior to intervention prompting us to suggest that spontaneous steinstrasse can be initially managed conservatively, as in ESWL-associated steinstrasse.

https://ift.tt/2OMQ4va

Trans-luminal repair of a ruptured AAA with Type Ia and Type II endoleaks

Abstract

Ruptured abdominal aortic aneurysm (rAAA) with an associated Type II endoleak is rare. Emergent surgical repair is often necessary and may be associated with high morbidity and mortality. We report an alternative unique trans-luminal repair strategy in an 84-year-old male who presented with a rAAA with prior EVAR, and Type Ia and Type II endoleaks. The operative strategy consisted of proximal endograft extension into the para-renal aorta, followed by staged sac embolization using glue. Postoperatively, the patient recovered well from the repair, and follow-up imaging demonstrated a stable repair.

https://ift.tt/2PmlTIr

A case of type II Mirizzi syndrome treated by simple endoscopic means

Abstract

Mirizzi syndrome is an uncommon complication of chronic cholelithiasis. Advancement in radiological modalities and minimally invasive surgery has led to improved pre-operative diagnoses and more laparoscopic cholecystectomies. But for unsuitable surgical candidates, endoscopy can be the definitive treatment. In this case, we present a 67-year-old man with type II Mirizzi syndrome treated by simple endoscopic means.

https://ift.tt/2OLzjk7

Abnormal Microvasculature in Laryngectomy Mucosal Margins may be Associated with Increased Risk of Fistula

Abstract

Pharyngocutaneous fistula after laryngectomy is common and significantly increases the morbidity of the procedure. Intraoperative, objective variables that can reliably predict fistula formation would be useful to surgeons deciding how to reconstruct the laryngectomy defect. Retrospective chart review of 50 radiated patients and 10 non-radiated patients who underwent total laryngectomy at a single tertiary care institution. Patients with pharyngocutaneous fistula were selected to ensure a representative sample were available for comparison. All patients had pathology slides available for re-review by a single, blinded pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges were examined for 7 histologic features, and odds ratios were calculated to assess whether these features were associated with fistula. When evaluating all 60 patients, both telangiectatic capillaries and hyalinized arterioles were associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between the variables was evaluated; findings indicated a high likelihood of having hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67 [3.13, 320.06]). Microvascular changes in radiated tissue have previously been described in other anatomic subsites, but the larynx and pharynx have not been specifically evaluated. Laryngectomy mucosal margins appear to display similar changes, and evidence of this damage may be associated with fistula formation. These features could potentially guide the surgeon to alter the reconstructive technique.

https://ift.tt/2NuK9WM

Abnormal Microvasculature in Laryngectomy Mucosal Margins may be Associated with Increased Risk of Fistula

Abstract

Pharyngocutaneous fistula after laryngectomy is common and significantly increases the morbidity of the procedure. Intraoperative, objective variables that can reliably predict fistula formation would be useful to surgeons deciding how to reconstruct the laryngectomy defect. Retrospective chart review of 50 radiated patients and 10 non-radiated patients who underwent total laryngectomy at a single tertiary care institution. Patients with pharyngocutaneous fistula were selected to ensure a representative sample were available for comparison. All patients had pathology slides available for re-review by a single, blinded pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges were examined for 7 histologic features, and odds ratios were calculated to assess whether these features were associated with fistula. When evaluating all 60 patients, both telangiectatic capillaries and hyalinized arterioles were associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between the variables was evaluated; findings indicated a high likelihood of having hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67 [3.13, 320.06]). Microvascular changes in radiated tissue have previously been described in other anatomic subsites, but the larynx and pharynx have not been specifically evaluated. Laryngectomy mucosal margins appear to display similar changes, and evidence of this damage may be associated with fistula formation. These features could potentially guide the surgeon to alter the reconstructive technique.

https://ift.tt/2NuK9WM

Abnormal Microvasculature in Laryngectomy Mucosal Margins may be Associated with Increased Risk of Fistula

Abstract

Pharyngocutaneous fistula after laryngectomy is common and significantly increases the morbidity of the procedure. Intraoperative, objective variables that can reliably predict fistula formation would be useful to surgeons deciding how to reconstruct the laryngectomy defect. Retrospective chart review of 50 radiated patients and 10 non-radiated patients who underwent total laryngectomy at a single tertiary care institution. Patients with pharyngocutaneous fistula were selected to ensure a representative sample were available for comparison. All patients had pathology slides available for re-review by a single, blinded pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges were examined for 7 histologic features, and odds ratios were calculated to assess whether these features were associated with fistula. When evaluating all 60 patients, both telangiectatic capillaries and hyalinized arterioles were associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between the variables was evaluated; findings indicated a high likelihood of having hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67 [3.13, 320.06]). Microvascular changes in radiated tissue have previously been described in other anatomic subsites, but the larynx and pharynx have not been specifically evaluated. Laryngectomy mucosal margins appear to display similar changes, and evidence of this damage may be associated with fistula formation. These features could potentially guide the surgeon to alter the reconstructive technique.

https://ift.tt/2NuK9WM

Torticollis as Presentation for Atypical Kawasaki Disease Complicated by Giant Coronary Artery Aneurysms

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. The diagnosis can be made in a patient who presents with a prolonged high fever and meeting at least four of five criteria including polymorphous rash, mucosal changes, extremity changes (including swelling and/or palmar and plantar erythema), bilateral nonsuppurative conjunctivitis, and unilateral cervical lymphadenopathy. Atypical KD refers to patients who have not met the full criteria and in whom atypical features may be present. We discuss a case of a 6-year-old male who presented to the Emergency Department with torticollis. A series of investigations for elevated inflammatory markers revealed dilated coronary artery aneurysms on echocardiogram, and thus he was diagnosed with atypical KD. His only other criteria were bilateral nonsuppurative conjunctivitis and a prior brief febrile illness. He was treated with high-dose intravenous immune globulin (IVIG) and low-dose aspirin. Low-molecular-weight heparin and atenolol were added due to the presence of giant aneurysms.

https://ift.tt/2E71TIA

Reflections on International Judicialization

Sands, P; (2016) Reflections on International Judicialization. European Journal of International Law , 27 (4) pp. 885-900. 10.1093/ejil/chw052 . Green open access

https://ift.tt/2C2swvu

A review of psychiatric co-morbidity described in genetic and immune mediated movement disorders

Peall, KJ; Lorentzos, MS; Heyman, I; Tijssen, MAJ; Owen, MJ; Dale, RC; Kurian, MA; (2017) A review of psychiatric co-morbidity described in genetic and immune mediated movement disorders. Neuroscience and Biobehavioral Reviews , 80 pp. 23-35. 10.1016/j.neubiorev.2017.05.014 . Green open access

https://ift.tt/2zXk4Mz

Loneliness in people with intellectual and developmental disorders across the lifespan: A systematic review of prevalence and interventions

Alexandra, P; Angela, H; Ali, A; (2018) Loneliness in people with intellectual and developmental disorders across the lifespan: A systematic review of prevalence and interventions. Journal of Applied Research in Intellectual Disabilities , 31 (5) pp. 643-658. 10.1111/jar.12432 .

https://ift.tt/2C5wRyi

Effects of bovine serum albumin on light activated antimicrobial surfaces

Oliveira Lourenco, CR; Macdonald, T; Gavriilidis, A; Allan, E; Macrobert, A; Parkin, I; (2018) Effects of bovine serum albumin on light activated antimicrobial surfaces. Rsc Advances , 8 pp. 34252-34258. 10.1039/c8ra04361b . Green open access

https://ift.tt/2zXeh9O

Going Public: Diversity Disclosures by Large Law Firms

Vaughan, S; (2015) Going Public: Diversity Disclosures by Large Law Firms. Fordham Law Review , 83 (5) pp. 2301-2324.

https://ift.tt/2C1CBc5

Preproglucagon Neurons in the Nucleus of the Solitary Tract are the Main Source of Brain GLP-1, Mediate Stress-Induced Hypophagia, and Limit Unusually Large Intakes of Food

Holt, MK; Richards, JE; Cook, DR; Brierley, DI; Williams, DL; Reimann, F; Gribble, FM; Holt, MK; Richards, JE; Cook, DR; Brierley, DI; Williams, DL; Reimann, F; Gribble, FM; Trapp, S; - view fewer (2018) Preproglucagon Neurons in the Nucleus of the Solitary Tract are the Main Source of Brain GLP-1, Mediate Stress-Induced Hypophagia, and Limit Unusually Large Intakes of Food. Diabetes , 67 (10) 10.2337/db18-0729 . Green open access

https://ift.tt/2zXjKgP

Line structure representation for road network analysis

Marshall, S; (2016) Line structure representation for road network analysis. Journal of Transport and Land Use , 9 (1) pp. 29-64. 10.5198/jtlu.2015.744 . Green open access

https://ift.tt/2C3mfQj

Melatonin as an Adjunct to Therapeutic Hypothermia in a Piglet Model of Neonatal Encephalopathy: a Translational Study

Robertson, NJ; Martinello, K; Lingam, I; Avdic-Belltheus, A; Meehan, C; Alonso-Alconada, D; Ragab, S; ... Facchinetti, F; + view all Robertson, NJ; Martinello, K; Lingam, I; Avdic-Belltheus, A; Meehan, C; Alonso-Alconada, D; Ragab, S; Bainbridge, A; Sokolska, M; Tachrount, M; Middleton, B; Price, D; Hristova, M; Golay, X; Soliani Raschini, A; Aquino, G; Pelizzi, N; Facchinetti, F; - view fewer (2018) Melatonin as an Adjunct to Therapeutic Hypothermia in a Piglet Model of Neonatal Encephalopathy: a Translational Study. Neurobiology of Disease (In press).

https://ift.tt/2zXq1t9

From the Guest Editors

Ali, A; Werner, S; (2017) From the Guest Editors. Journal of Mental Health Research in Intellectual Disabilities , 10 (2) pp. 51-54. 10.1080/19315864.2017.1294850 . Green open access

https://ift.tt/2C2uP1I

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Hiley, CT; Le Quesne, J; Santis, G; Sharpe, R; De Castro, DG; Middleton, G; Swanton, C; (2016) Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease. The Lancet , 388 (10048) pp. 1002-1011. 10.1016/S0140-6736(16)31340-X . Green open access

https://ift.tt/2zXJY35

Oscillatory Beta Power Correlates With Akinesia-Rigidity in the Parkinsonian Subthalamic Nucleus

Beudel, M; Oswal, A; Jha, A; Foltynie, T; Zrinzo, L; Hariz, M; Limousin, P; Beudel, M; Oswal, A; Jha, A; Foltynie, T; Zrinzo, L; Hariz, M; Limousin, P; Litvak, V; - view fewer (2017) Oscillatory Beta Power Correlates With Akinesia-Rigidity in the Parkinsonian Subthalamic Nucleus. Movement Disorders , 32 (1) pp. 174-175. 10.1002/mds.26860 .

https://ift.tt/2C0bBd7

Very early onset IBD: novel genetic aetiologies

Purpose of review To summarize the current understanding and recent advances on the genetic aetiology in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD). Recent findings IBD is a chronic disorder of the gastrointestinal tract whose manifestation is a result of complex interactions between genetics, environment, immune system and microbial flora. Over 230 IBD risk loci have been reported in genome wide association studies but the genetic contribution of the majority of these loci in the manifestation of IBD is very low. Patients with VEO-IBD present with a more severe disease than older patients, characterized by poor prognosis and failure of conventional therapy. Recent studies have reported several monogenic diseases with high penetrance that present with IBD and IBD-like intestinal manifestations and overlap with primary immunodeficiencies. Increasing body of evidence supports a prominent role of genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD are reviewed and current challenges in therapy with potential strategy to manage the disease are discussed. Summary Functional analysis of the genes implicated in monogenic IBD has increased the understanding of the underlying pathobiological mechanism of the disease. This knowledge can be used to personalize medicine for specific patients, improving the standard of care and quality of life. Correspondence to Aleixo M. Muise, MD, PhD, FRCPC, 555 University Ave, Toronto, ON M5G 1X8. Tel: +416-813-7654 X306171; e-mail: aleixo.muise@sickkids.ca Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NuDkVh

Biological treatments for severe asthma: where do we stand?

Purpose of review For patients with severe asthma, disease control is not achieved resulting in persistent morbidity and risks for exacerbations. The advent of biologics is providing a new form of treatment for many with severe asthma. Recent findings Four mAb biologics are approved for clinical use: omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab, reslizumab, and benralizumab). These four biologics target components of the type 2-inflammatory pathway which is reflected by biomarkers: peripheral blood eosinophils and exhaled nitric oxide. In severe asthma, biologics have reduced asthma exacerbations. The antieosinophilic biologics have also improved lung function. The safety profile of these biologics has been good. Summary For patients with severe asthma and biomarkers indicating a type 2 inflammatory pathway, the addition of biologics has proven to be an effective approach to achieve disease control and is an appropriate next step treatment. Correspondence to William W. Busse, MD, Professor of Medicine, University of Wisconsin Hospitals and Clinics, 600 Highland Avenue, Madison, WI 53792, USA. E-mail: wwb@medicine.wisc.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2y6nxaf

Very early-onset inflammatory bowel disease: an integrated approach

Purpose of the review Immune dysregulation disorders are among the most rapidly growing set of inborn errors of immunity. One particular subset is the category where early-onset inflammatory bowel disease (IBD) is the most common manifestation. These disorders are being increasingly appreciated although there has been minimal effort to articulate a unified approach to their diagnosis and management. This review will cover current thinking and strategies related to diagnosis and management of very early-onset IBD. Recent findings There is an expanding set of monogenic causes of early-onset IBD. In many cases, the precise genetic cause dictates management. Lessons learned from the management of these monogenic conditions can sometimes be extrapolated to other refractory cases of IBD. Summary An integrated approach to diagnosis, risk analysis, and management can include diagnostic approaches not often utilized for traditional IBD such as whole exome sequencing. Management can also include nontraditional approaches such as targeted biologics or hematopoietic cell transplantation. Correspondence to Kathleen E. Sullivan, MD, PhD, Immunology, ARC 1216-I, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA. Tel: +1 215 590 1697; fax: +1 267 426 0363; e-mail: sullivank@email.chop.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NusApP

Secondary antibody deficiency in neurology

Purpose of review Induction of lymphocyte depletion is increasingly used as a therapeutic strategy for central and peripheral neuroinflammatory disease. However, there is also a growing recognition of the treatment-related complication of secondary antibody deficiency (SAD). Although the occurrence of hypogammaglobulinaemia is a recognized phenomenon during immunomodulation, robust data on the coexistence of impaired responses to immunization, and significant and/or atypical infections is scarce. Here we review the literature on SAD in anti-CD20 therapy. Recent findings Several factors that may increase the incidence of SAD have now been identified, including low levels of immunoglobulins prior to the commencement of B-cell ablation therapy, duration of maintenance therapy, and concurrent or prior use of other immunosuppressing agents such as cyclophosphamide and steroids. Measurement of disease-specific antibodies and vaccine response are likely to be helpful adjuncts to measurement of serum immunoglobulin levels during B-cell depleting therapy. Supportive treatment may include amending the treatment schedule to limit cumulative dose. Summary B-cell depleting agents offer considerable therapeutic benefit in neurology. We propose modifications in current practice that include risk stratification and early identification of SAD, with the aim of minimising morbidity and mortality related to this underappreciated condition. Correspondence to Dr Emma C. Tallantyre, Department of Psychological Medicine and Clinical Neurosciences, B4-C4 Corridor, University Hospital of Wales, Cardiff, CF14 4XW, Wales, UK. Tel: +44 02920 745403; e-mail: tallantyreec@cardiff.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2y8uR5f

Advances in site-specific gene editing for primary immune deficiencies

Purpose of review Conventional gene therapy has been a successful, curative treatment modality for many primary immune deficiencies with significant improvements in the last decade. However, the risk of leukemic transformation with viral-mediated gene addition still remains, and unregulated gene addition is not an option for certain diseases in which the target gene is closely controlled. The recent bloom in genome modification platforms has created the opportunity to site-specifically correct mutated DNA base pairs or insert a corrective cDNA minigene while maintaining gene expression under control of endogenous regulatory elements. Recent findings There is an abundance of ongoing research utilizing programmable nucleases to facilitate site-specific gene correction of many primary immune deficiencies including X-linked severe combined immune deficiency, X-linked chronic granulomatous disease, Wiskott–Aldrich syndrome, X-linked hyper-IgM syndrome, X-linked agammaglobulinemia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked. In all, these studies have demonstrated the ability to integrate corrective DNA sequences at a precise location in the genome at rates likely to either cure or ameliorate disease. Summary Gene editing for primary immune deficiency (PID) has advanced to the point to that translation to clinical trials is likely to occur in the next several years. At the current pace of research in DNA repair mechanisms, stem cell biology, and genome-editing technology, targeted genome modification represents the next chapter of gene therapy for PID. Correspondence to Caroline Y. Kuo, MD, Division of Allergy and Immunology, Department of Pediatrics, 10833 Le Conte, MDCC 12-430, Los Angeles, CA 90095, USA. Tel: +1 310 825 6481; fax: +1 310 825 9832; e-mail: ckuo@mednet.ucla.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NpC6e5

Very early onset IBD: novel genetic aetiologies

Purpose of review To summarize the current understanding and recent advances on the genetic aetiology in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD). Recent findings IBD is a chronic disorder of the gastrointestinal tract whose manifestation is a result of complex interactions between genetics, environment, immune system and microbial flora. Over 230 IBD risk loci have been reported in genome wide association studies but the genetic contribution of the majority of these loci in the manifestation of IBD is very low. Patients with VEO-IBD present with a more severe disease than older patients, characterized by poor prognosis and failure of conventional therapy. Recent studies have reported several monogenic diseases with high penetrance that present with IBD and IBD-like intestinal manifestations and overlap with primary immunodeficiencies. Increasing body of evidence supports a prominent role of genetics in the onset of VEO-IBD. New genetic variants and diagnoses in VEO-IBD are reviewed and current challenges in therapy with potential strategy to manage the disease are discussed. Summary Functional analysis of the genes implicated in monogenic IBD has increased the understanding of the underlying pathobiological mechanism of the disease. This knowledge can be used to personalize medicine for specific patients, improving the standard of care and quality of life. Correspondence to Aleixo M. Muise, MD, PhD, FRCPC, 555 University Ave, Toronto, ON M5G 1X8. Tel: +416-813-7654 X306171; e-mail: aleixo.muise@sickkids.ca Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NuDkVh

Biological treatments for severe asthma: where do we stand?

Purpose of review For patients with severe asthma, disease control is not achieved resulting in persistent morbidity and risks for exacerbations. The advent of biologics is providing a new form of treatment for many with severe asthma. Recent findings Four mAb biologics are approved for clinical use: omalizumab (anti-IgE) and three antieosinophilic interventions (mepolizumab, reslizumab, and benralizumab). These four biologics target components of the type 2-inflammatory pathway which is reflected by biomarkers: peripheral blood eosinophils and exhaled nitric oxide. In severe asthma, biologics have reduced asthma exacerbations. The antieosinophilic biologics have also improved lung function. The safety profile of these biologics has been good. Summary For patients with severe asthma and biomarkers indicating a type 2 inflammatory pathway, the addition of biologics has proven to be an effective approach to achieve disease control and is an appropriate next step treatment. Correspondence to William W. Busse, MD, Professor of Medicine, University of Wisconsin Hospitals and Clinics, 600 Highland Avenue, Madison, WI 53792, USA. E-mail: wwb@medicine.wisc.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2y6nxaf

Very early-onset inflammatory bowel disease: an integrated approach

Purpose of the review Immune dysregulation disorders are among the most rapidly growing set of inborn errors of immunity. One particular subset is the category where early-onset inflammatory bowel disease (IBD) is the most common manifestation. These disorders are being increasingly appreciated although there has been minimal effort to articulate a unified approach to their diagnosis and management. This review will cover current thinking and strategies related to diagnosis and management of very early-onset IBD. Recent findings There is an expanding set of monogenic causes of early-onset IBD. In many cases, the precise genetic cause dictates management. Lessons learned from the management of these monogenic conditions can sometimes be extrapolated to other refractory cases of IBD. Summary An integrated approach to diagnosis, risk analysis, and management can include diagnostic approaches not often utilized for traditional IBD such as whole exome sequencing. Management can also include nontraditional approaches such as targeted biologics or hematopoietic cell transplantation. Correspondence to Kathleen E. Sullivan, MD, PhD, Immunology, ARC 1216-I, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA. Tel: +1 215 590 1697; fax: +1 267 426 0363; e-mail: sullivank@email.chop.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NusApP

Secondary antibody deficiency in neurology

Purpose of review Induction of lymphocyte depletion is increasingly used as a therapeutic strategy for central and peripheral neuroinflammatory disease. However, there is also a growing recognition of the treatment-related complication of secondary antibody deficiency (SAD). Although the occurrence of hypogammaglobulinaemia is a recognized phenomenon during immunomodulation, robust data on the coexistence of impaired responses to immunization, and significant and/or atypical infections is scarce. Here we review the literature on SAD in anti-CD20 therapy. Recent findings Several factors that may increase the incidence of SAD have now been identified, including low levels of immunoglobulins prior to the commencement of B-cell ablation therapy, duration of maintenance therapy, and concurrent or prior use of other immunosuppressing agents such as cyclophosphamide and steroids. Measurement of disease-specific antibodies and vaccine response are likely to be helpful adjuncts to measurement of serum immunoglobulin levels during B-cell depleting therapy. Supportive treatment may include amending the treatment schedule to limit cumulative dose. Summary B-cell depleting agents offer considerable therapeutic benefit in neurology. We propose modifications in current practice that include risk stratification and early identification of SAD, with the aim of minimising morbidity and mortality related to this underappreciated condition. Correspondence to Dr Emma C. Tallantyre, Department of Psychological Medicine and Clinical Neurosciences, B4-C4 Corridor, University Hospital of Wales, Cardiff, CF14 4XW, Wales, UK. Tel: +44 02920 745403; e-mail: tallantyreec@cardiff.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2y8uR5f

Advances in site-specific gene editing for primary immune deficiencies

Purpose of review Conventional gene therapy has been a successful, curative treatment modality for many primary immune deficiencies with significant improvements in the last decade. However, the risk of leukemic transformation with viral-mediated gene addition still remains, and unregulated gene addition is not an option for certain diseases in which the target gene is closely controlled. The recent bloom in genome modification platforms has created the opportunity to site-specifically correct mutated DNA base pairs or insert a corrective cDNA minigene while maintaining gene expression under control of endogenous regulatory elements. Recent findings There is an abundance of ongoing research utilizing programmable nucleases to facilitate site-specific gene correction of many primary immune deficiencies including X-linked severe combined immune deficiency, X-linked chronic granulomatous disease, Wiskott–Aldrich syndrome, X-linked hyper-IgM syndrome, X-linked agammaglobulinemia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked. In all, these studies have demonstrated the ability to integrate corrective DNA sequences at a precise location in the genome at rates likely to either cure or ameliorate disease. Summary Gene editing for primary immune deficiency (PID) has advanced to the point to that translation to clinical trials is likely to occur in the next several years. At the current pace of research in DNA repair mechanisms, stem cell biology, and genome-editing technology, targeted genome modification represents the next chapter of gene therapy for PID. Correspondence to Caroline Y. Kuo, MD, Division of Allergy and Immunology, Department of Pediatrics, 10833 Le Conte, MDCC 12-430, Los Angeles, CA 90095, USA. Tel: +1 310 825 6481; fax: +1 310 825 9832; e-mail: ckuo@mednet.ucla.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NpC6e5

Effect of methotrexate monotherapy on T‐cell subsets in the peripheral circulation in psoriasis

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2C1TRhq

Linear nail bed dyschromia: a distinctive dermoscopic feature of nail lichen planus

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2zYQTsH

Asymptomatic solitary mass on the sacral region

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2C4ji24

Acitretin: a promising therapy for localized childhood lichen myxoedematosus

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2zY4osp

Hypopigmented patches in childhood: do not forget mycosis fungoides

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2C4jazC

Bullous pyoderma gangrenosum secondary to underlying multiple myeloma: treated with ciclosporin

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2zY4i41

Sporadic case of Darier disease caused by a novel splice‐site mutation in the ATP2A2 gene

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2BZoUKV

A survey of the treatment and management of patients with severe chronic spontaneous urticaria

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2zXt2JW

Alteration of serum and tissue tumor necrosis factor alpha levels: A possible mechanism of action of oral pulse steroids in the treatment of alopecia areata

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2NsKcTa

Improvement of alopecia areata with apremilast

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2QB04oB

Chondrodysplasia punctata (CDPX2) in a male caused by single‐gene mosaicism: A 20‐year follow‐up

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2O9NUGo

Sentinel lymph node biopsy remains the most accurate method of obtaining staging and prognostic information for patients with primary cutaneous melanomas

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2QAcrBd

Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416 patients

International Journal of Dermatology, EarlyView.


https://ift.tt/2C296Hc

Issue Information

International Journal of Dermatology, Volume 57, Issue 11, Page i-iii,1273-1274, November 2018.


https://ift.tt/2zXVECN

Rare case of adult pancreatic haemangioma and literature review

Pancreatic haemangiomas are benign vascular tumours very rare in adults. Twenty-two cases are described in the literature. The symptoms are non-specific, and therefore rarely clinically suspected, and the vast majority are incidental findings in imaging tests such as ultrasound, CT, angiography or MRI. They appear on CT as a cystic lesion with contrast enhancement in the arterial phase. We present the case of a 36-year-old male patient with no history of disease, referred with lumbar pain and suspected renal calculus after tomography showing hypervascular enhancement in the pancreatic body and infiltrative lesion (possible neuroendocrine neoplasia) on MRI and biliopancreatic echoendoscopy. He was submitted to laparotomy with subtotal pancreatectomy and splenectomy and satisfactory evolution.

https://ift.tt/2C2a8D3

Uncommon manifestation of leptospirosis: a diagnostic challenge

Leptospirosis is a zoonotic disease commonly affecting the tropical countries. It may have protean clinical manifestations including hepatorenal dysfunction, myocarditis, pulmonary haemorrhage, meningitis, optic neuritis and rhabdomyolysis. Neurological manifestation of leptospirosis without the classical hepatorenal dysfunction is a rare entity. This complication of leptospirosis can present with diverse central and peripheral neurological presentations. The overlapping clinical manifestations with many common tropical pathogens often pose diagnostic dilemma and delay in definitive therapy may lead to adverse clinical consequences. We report a case of a 19-year-old man with no prior comorbidities presenting with high-grade fever and altered sensorium. He was diagnosed to be a probable case of leptospirosis, based on all available test results and by fulfilment of parameters under modified Faine's criteria. The patient was successfully managed and discharged in stable condition.

https://ift.tt/2zYpfMn

Isoniazid-induced pure red cell aplasia

The pure red cell aplasia (PRCA) is an uncommon side effect of isoniazid. We describe a 28-year-old man who developed a severe anaemia caused by PRCA. The patient received antituberculous therapy including isoniazid for his pulmonary tuberculosis. On discontinuation of isoniazid, the anaemia recovered promptly. PRCA should be considered in case of unexplained anaemia during isoniazid treatment.

https://ift.tt/2C21JPT

Solitary vallecular neurofibroma presenting with respiratory obstruction: an unusual presentation

An occurrence of vallecular neurofibroma with airway obstruction is extremely rare and to the best of our knowledge, no case report has been documented in the literature to date. Although microlaryngeal surgery with cold knife excision is the standard surgical procedure offered to patients of vallecular lesions, it can be successfully managed with the help of endoscopic coblation as later can provide a bloodless surgical field preventing the unmet need for the tracheostomy and reducing the postoperative morbidities.

https://ift.tt/2zYp97t

RCC in cross ectopic kidney: a challenging diagnosis and management

Description 

A 57-year-old woman with a 5-month history of left-upper quadrant (LUQ) abdominal pain was referred after a retroperitoneal mass was discovered on CT scan of the abdomen and pelvis. Clinical history revealed mild LUQ abdominal pain over the course of 5 months, associated with anorexia, unintended weight loss and several episodes of painless gross haematuria. Physical examination was positive for an ill-defined mass in the LUQ extending to the umbilical region. Routine laboratory tests did not reveal abnormal findings except for microscopic haematuria. CT scan images revealed a left cross ectopic kidney fusing laterally with the lower pole of right kidney in addition to a mass measuring 7.5x8.5 cm emerging from the ectopic kidney. The mass extended to the left flank crossing the abdominal aorta and passing behind the inferior mesenteric artery. This structure mimicked a horseshoe kidney (figures 1 and 2). Retrograde pyelography confirmed...

https://ift.tt/2C21zIh

Woman with lower back pain, SIADH and a twist of Lyme

A 62-year-old woman was admitted with a 3-week history of atraumatic bilateral lower back pain, progressive ascending flaccid paralysis, hyponatraemia and constipation. She was otherwise in good health with only a recent diagnosis of acute gastroenteritis that preceded her presenting symptoms. Her initial laboratory evaluation was consistent with Syndrome of Inappropriate Antidiuretic Hormone (SIADH) but was otherwise unremarkable. MRI of the spine revealed bilateral diffuse nerve root enhancement from at least C6 to the conus level, suggesting an inflammatory process. Lumbar puncture demonstrated high protein (629 mg/dL) with marked pleocytosis (363 cells/mcL) incompatible with albuminocytological dissociation typically seen in Guillain-Barre syndrome. A thorough diagnostic evaluation was undertaken to explore potential infectious, malignant and autoimmune conditions. Lyme disease serology (ELISA and Western Blot, IgM and IgG) was positive leading to a final diagnosis of lymphocytic meningoradiculitis or Bannwarth syndrome.

https://ift.tt/2zYykVE

Large mesenteric lymphangioma in an adult patient: an unusual presentation of a rare disease

Lymphangiomas are most commonly described as a small painless mass in the neck or a vesicular rash in an infant patient. Ninety per cent of cases are diagnosed before the age of 2. Treatment usually involves surgical resection. Intra-abdominal lymphangiomas and mesenteric lymphangiomas, as described in our case report, represent a rare pathology. The exact prevalence of this condition is unclear but it has been suggested in the literature that there have been as few as 820 cases since the 16th century. The clinical presentation is usually subacute and diagnosis made incidentally during a workup of chronic gastrointestinal symptoms. Acute abdominal symptoms, as in our case presentation, are unusual but may be explained by the mass effect of a large intra-abdominal lesion. Cross-sectional imaging is key in preoperative workup and operative planning. Complete surgical resection is recommended and curative in the majority of cases with a low risk of local recurrence.

https://ift.tt/2C21mEZ

Pericardial sarcoma

Pericardial sarcomas are extremely rare aggressive neoplasms. Non-specific symptoms and incidental discovery are usually the rule. Multimodality imaging is extremely important for diagnosis and tissue characterisation of all cardiac masses. Despite treatment, pericardial sarcomas are considered extremely fatal. We encountered a 27-year-old female patient who presented to our facility with progressive dyspnoea. On examination, clinical signs of cardiac tamponade were appreciated, transthoracic echocardiography revealed a tamponading pericardial effusion and a large heterogeneous pericardial mass. Pericardiocentesis revealed haemorrhagic fluid. Subsequently, CT revealed a pericardial mass compressing the right atrium. Excision biopsy showed a well-circumscribed mass, and cut sections showed friable grey–white tissue with areas of haemorrhage and necrosis. Pathological examination confirmed the diagnosis of high-grade undifferentiated sarcoma of the pericardium. The patient was started on adjuvant chemotherapy and radiotherapy. Follow-up after 1 year showed no relapse.

https://ift.tt/2zXreAE

Cutis marmorata telangiectatica congenita with skin ulceration: a rare benign skin vascular malformation

Description 

Cutis marmorata telangiectatica congenita (CMTC) is a sporadic congenital disorder characterised by localised or generalised cutaneous vascular anomaly. CMTC was first described in 1922 by Van Lohuizen as a pattern of reticulate erythema and telangiectasia infrequently associated with skin atrophy and/or ulceration.1 It is a rare benign skin lesion that is often apparent at birth with more than 50% of patients with CMTC having variations of associated defects. Body asymmetry is the most common (33%) associated anomaly reported.1

A 5-day-old female baby was born at term following an uneventful pregnancy. At birth, she weighed 2800 g, and her growth profile was appropriate for her age. Her general physical examination was unremarkable except for the appearance of a 3x4 cm bluish-purple skin lesion over the right knee. The skin lesion had erythematous reticulated appearance at the periphery and ulceration at the centre with subcutaneous atrophy (

https://ift.tt/2C0uWuK

Strangulated urethral prolapse in a postmenopausal woman presenting as acute urinary retention

Description 

A 48-year-old woman presented with acute urinary retention for 1 day and severe periurethral pain for last 3 days. She also revealed a history of occasional blood spotting of undergarments, dysuria and a protruding mass from the urethra for the last 3 months. Her medical/surgical and personal histories were unremarkable. Her obstetric history revealed presence of three normal vaginal deliveries and menopause at the age of 45 years. Local examination revealed presence of irreducible dusky red oedematous tender donut-shaped swelling measuring 2x2 cm around the urethral orifice suggestive of strangulated urethral prolapse (figure 1). A gentle attempt at reduction of the prolapsed mass was done under sedation which was successful following which a Foley catheter was placed. Cystourethroscopy revealed excess urethral mucosa with normal bladder mucosa. Ultrasonography of the abdomen was suggestive of normal bladder parameters with bilateral normal upper tracts. After proper counselling and consent, the patient was taken for surgery under general anaesthesia....

https://ift.tt/2zYp43F