Erythema elevatum diutinum in a healthy child

http://ift.tt/2nXJxfR

Focal dermal hypoplasia: inheritance from father to daughter

http://ift.tt/2olWXWv

Primary cutaneous nocardiosis caused by Nocardia brasiliensis following a wasp sting

Summary

We report a case of an 87-year-old woman who presented with painful erythema of her right forearm 10 days after she had been stung by a wasp on her right hand. The lesion had rapidly deteriorated during the week before presentation, and treatment with antibiotics and glucocorticoids did not improve the condition. After careful evaluation, we performed cultures from the lesion aspiration, and morphological and genetic analysis of bacteria cultures confirmed a bacterial infection with Nocardia brasiliensis. The patient recovered after 3 weeks. Primary cutaneous nocardiosis due to Nocardia spp. is relatively uncommon in clinics, but it was the distance of the lesions from the affected area of the wasp sting that has made this an even rarer case and of interest to report.

http://ift.tt/2nXyKlP

The role of fillers in the management of acne scars

Summary

Acne scars are present in 95% of patients with acne, and can cause profound psychosocial morbidity. Fillers are commonly used for facial soft tissue augmentation, and there is increasing interest in their use for the treatment of acne scars, particularly for the atrophic subtype. We review the evidence for the use of temporary, semi-permanent and permanent fillers for acne scars. The use of permanent methylmethacrylate fillers for acne scarring is supported by a randomized controlled trial, and is approved by the United States Food and Drug Administration. There is initial evidence supporting the use of poly-L-lactic acid and hyaluronic acid fillers, but evidence is still lacking about the use of polyacrylamide and polyalkylimide fillers.

http://ift.tt/2om0PXb

An unusual and potentially fatal cause of scalp crusting

http://ift.tt/2om5ybx

Extensive levamisole-induced vasculitis

Summary

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman.

http://ift.tt/2nXyJON

‘Super bloom’ dermatitis

http://ift.tt/2olW7ZO

Role of nail bed methotrexate injections in isolated nail psoriasis: conventional drug via an unconventional route

Summary

Nail psoriasis can be a debilitating condition; however, in patients with isolated nail involvement, the use of toxic systemic therapies such as methotrexate may not be justified. We report on 4 patients (30 involved nails between them), who were treated with injections of methotrexate (0.1 mL of a 25 mg/mL solution) into the nail bed at 3-weekly intervals. Mean baseline Nail Psoriasis Severity Index (NAPSI) was 4.77 (range 2–8, cumulative score 143; n = 30); dropping successively at each visit to 2.43 (range 0–4, cumulative score 73; n = 30) at 15 weeks. The decline in mean NAPSI from 4.87 to 2.17 was statistically significant (P < 0.001; Friedman analysis). Reported adverse effects were pain, injection site pigmentation and nail bed haemorrhage. Administration of specific targeted therapy to the nail bed may help manage nail psoriasis effectively.

http://ift.tt/2nXNIrY

Change of somatosensory function of the tongue caused by chorda tympani nerve disorder after stapes surgery

Objectives

Patients after middle ear surgery often complain of taste disturbance and a lingual numbness. The purpose of this study was to objectively assess changes in the somatosensation of the tongue and taste function in patients undergoing stapes surgery.

Study Design

Prospective study.

Methods

Symptoms of taste disturbance and tongue numbness after surgery were investigated before and after surgery in 41 patients (13 males, 28 females; mean age 41.8 years) who underwent stapes surgery. Twenty-eight patients (9 males, 19 females; mean age 43.1 years) underwent sensory and taste function tests before and after surgery. Sensory function of the tongue was measured at the operated side and the nonoperated side using the 2-point discrimination test and an electrostimulator test. Taste function was assessed with electrogustometry (EGM).

Results

The chorda tympani nerve (CTN) was gently touched or stretched in all patients. Postoperative thresholds on the operated side were significantly higher than preoperative thresholds in all tests in the patients who underwent all three kinds of tests. Tongue somatosensory symptoms improved significantly earlier than the taste disturbance postoperatively, and the sensory thresholds returned to the baseline along with recovery of symptoms.

Conclusion

These findings suggest that dysfunction of the CTN occurred following surgery even when the CTN was preserved, and that the sensory nerve threshold of the tongue correlated with the symptom of lingual numbness. The CTN may play a role not only in taste function but also in the somatosensory function of the tongue.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2oZTdeo

Sinus procedures in the Medicare population from 2000 to 2014: A recent balloon sinuplasty explosion

Objective

To describe sinus procedure trends from 2000 to 2014, particularly following the introduction of balloon sinuplasty Common Procedural Technology (CPT) codes in 2011.

Study Design

Retrospective review of Medicare billing data available to the public.

Methods

Procedure and beneficiary data from 2000 to 2014 and provider data from 2012 to 2014 were obtained online from the Centers for Medicare and Medicaid Services. Sinus CPT codes were classified as balloon sinus procedure (BSP) or nonballoon sinus procedure (nBSP). Providers billing for sinus procedures were categorized as BSP only, nBSP only, or both. For comparison, data on septoplasty procedures from 2000 to 2014 were obtained.

Results

From 2000 to 2014, the total number of sinus procedures per 10 thousand beneficiaries (PP10K) nationwide increased by 3.7% annually. From 2011 to 2014, nBSP PP10K decreased by 3.1% annually, and BSP PP10K increased by 59% annually. Septoplasty PP10K changed by < 1% annually between 2000 and 2014. States with the highest BSP PP10K from 2012 to 2014 were Kansas, Texas, and Louisiana. Providers performing sinus procedures increased by 30.9% from 2012 to 2014. There was a 244% increase in BSP-only providers, a 0.7% increase in nBSP-only providers, and an 83.3% increase in providers using both. Septoplasty providers increased by 4.1%.

Conclusion

Although the total number of sinus procedures increased from 2000 to 2014, the number of BSP increased at a substantially greater rate since the introduction of CPT codes for these procedures in 2011. Nationwide increases in sinus providers were driven by new providers performing balloon-guided procedures.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2p087Ry

Polydioxanone plates are safe and effective for L-strut support in functional septorhinoplasty

Objectives/Hypothesis

To evaluate the safety, efficacy, and result stability of polydioxanone (PDS) plate use for L-strut stabilization.

Study Design

Retrospective analysis of a prospective cohort.

Methods

Patients who underwent functional septorhinoplasty with the use of PDS plates between January 2013 and January 2017 were administered the Nasal Obstruction Symptom Evaluation (NOSE) scale pre- and postoperatively at 2, 4, 6, and 12 months. Patient demographics, reason for PDS use, graft type, complications, and outcomes were analyzed.

Results

Eighty-eight patients aged 34.3 years (standard deviation [SD] = 15.7 years; range, 7.5–71.5 years) were included. All patients were found to have a fracture and/or severe deviation of the L-strut for which the PDS plate was used for rigid support. Mean preoperative NOSE score 65.2 (SD = 22.1) significantly decreased to 19.6 (SD = 21.6) at 7.2 months (SD = 5.5 months) postoperatively. There were no significant differences in NOSE scores between follow-up time points. There was one complication, a septal abscess, and one revision.

Conclusions

A PDS plate is a safe and effective material to be utilized in functional septorhinoplasty for patients with a fracture or iatrogenic injury to the septal L-strut or poor quality septal cartilage that requires stability without additional width. Outcomes are stable at 6 and 12 months, after the plate has dissolved. The use of a PDS plate may decrease the need for rib grafting in patients with a history of previous septoplasty and persistent nasal obstruction with a dorsal or caudal C-shaped septal deformity or fracture of the L-strut.

Level of Evidence

2c Laryngoscope, 2017

http://ift.tt/2olypLm

Recent trends in oropharyngeal cancer funding and public interest

Objectives/Hypothesis

The incidence of oropharyngeal cancer (OPC) has increased in the United States. This has been driven by an increase in human papillomavirus (HPV)-positive OPC. Our objective is to determine trends in National Institutes (NIH)-supported research funding and public interest in OPC.

Methods

The NIH Research Portfolio Online Reporting Tools database was evaluated for projects related to OPC between 2004 and 2015. Projects were evaluated for total funding, relation to HPV, principal investigator departmental affiliation and degree, and NIH agency or center responsible for grant. The Google Trends database was evaluated for relative Internet search popularity of oropharyngeal cancer and related search terms between 2004 and 2015.

Results

In terms of NIH funding, 100 OPC-related projects representing 242 grant years and $108.5 million were funded between 2004 and 2015. Total NIH funding for OPC projects increased from $167,406 in 2004 to $16.2 million in 2015. Funding for HPV-related OPC increased from less than $2 million yearly between 2004 and 2010 up to $12.7 million in 2015. Principal investigators related to radiation oncology ($41.8 million) and with doctor of medicine degrees ($52.8 million) received the largest share of total funding. Relative Internet search popularity for oropharyngeal cancer has increased from 2004 to 2015 compared to control cancer search terms.

Conclusion

Increased public interest and NIH funding has paralleled the rising incidence of OPC. NIH funding has been driven by projects related to the role of HPV in OPC.

Level of Evidence

2c. Laryngoscope, 2017

http://ift.tt/2olrKB1

MRI surveillance of vestibular schwannomas without contrast enhancement: Clinical and economic evaluation

Objectives

To determine if high-resolution T2-weighted (HRT2) magnetic resonance imaging (MRI) is a comparably accurate and economical alternative to the gold standard of contrast-enhanced T1-weighted (T1C) MRI for surveillance of know vestibular schwannomas (VSs).

Study Design

Retrospective case-control analysis, systematic review, and economic evaluation.

Methods

Vestibular schwannoma size in anteroposterior, mediolateral, and superoinferior axes were measured by two neuroradiologists, both blinded to previous measurements, for 50 randomized patients with T1C and HRT2 on two separate occasions. Measurements were assessed by Pearson product-moment correlation coefficients, and differences were analyzed by Student t test. Once the data were analyzed, appropriate economic evaluation was performed utilizing institutional-, federal-, and literature-based estimates of cost and incidence/prevalence.

Results

Pearson correlations (r) between T1C and HRT2 were 0.991 and 0.973 for radiologists 1 and 2, respectively, with no statistically significant differences (P ≤ 0.05) between imaging techniques. Intraobserver and interobserver reliability estimates (κ) were 0.88 to 1 for both T1C and HRT2, indicating very high reliability. Cost-minimization analysis demonstrated cost and charge differences of $148.02 and $1,284 per patient per scan, respectively. This represents an overall cost and charge savings for this 50-patient cohort of $7,401 and $64,200, respectively.

Conclusion

HRT2 imaging is a highly reliable and lower-cost alternative to T1C for follow-up surveillance scans in patients with VS.

Level of Evidence

2C. Laryngoscope, 2017

http://ift.tt/2p09Czs

Microbiomes of the normal middle ear and ears with chronic otitis media

Objective

The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media.

Study Design

Prospective multicenter cohort study.

Methods

All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan).

Results

In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears.

Conclusion

The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation.

Level of Evidence

2b. Laryngoscope, 2017

http://ift.tt/2olK2lK

Oral sensory dysfunction following radiotherapy

Objectives/Hypothesis

To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls.

Study Design

Cross-sectional cohort comparison.

Methods

Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts.

Results

Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P < .001 for all comparisons). Combining all four subsites into a single metric to assess an overall level of oral tactile dysfunction, the XRT cohort had reduced sensation by 18.7 dB (P < .001).

Conclusions

After radiation therapy, the oral cavity and oropharynx exhibit global tactile sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB.

Level of Evidence

3b. Laryngoscope, 2017

http://ift.tt/2oZVExg

Does incidental mastoid opacification on computerized tomography necessitate referral to ENT?

Objective

The prevalence of incidental temporal bone disease on magnetic resonance imaging has been widely reported in the medical literature. Despite this, there currently is little evidence regarding incidental otological disease on computerized tomography (CT). Thus, the study aimed to review the CT prevalence of asymptomatic adult ear disease and evaluate the appropriateness of ear, nose, and throat (ENT) referral following its discovery.

Study Design

Retrospective observational study of 468 CT scans.

Methods

All CT head scans performed between January 2015 and January 2016 containing the keyword mastoid in the radiological report initially were recruited for the study. Scans performed in the pediatric population following head trauma or for otological indications were excluded, leaving 468 eligible radiological images. The presence of prior otological disease or referral subsequently was established using electronic patient records.

Results

Mastoid and/or middle ear opacification was noted to be present in 62 patients (13%). Of these patients, 10 subsequently were found to have prior otological intervention or review. Following exclusion of these patients, the rate of incidental temporal bone disease was recorded as 11%.

Conclusion

Data from this study suggests that incidental findings in an asymptomatic individual do not necessitate referral or further intervention. Furthermore, it is the author's recommendation that radiological findings be closely correlated with clinical examination to reduce false diagnosis and inappropriate referral to ENT.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2olIlot

Asian and non-Asian disparities in outcomes of non-nasopharyngeal head and neck cancer

Objectives/Hypothesis

To evaluate disparities in overall survival (OS) between Asian and non-Asian patients diagnosed with non-nasopharyngeal head and neck cancer (HNC).

Study Design

This was a population-based, retrospective study of patients diagnosed with non-nasopharyngeal HNC of squamous cell carcinoma histology between 2001 and 2010 in British Columbia, Canada.

Methods

Using Kaplan-Meier methods and Cox regression models, we examined the relationship between race and OS.

Results

A total of 3,036 patients were included in the study. Median age was 64 years, 74% were men, and 7% were Asians. Asians had worse Eastern Cooperative Oncology Group (ECOG) status (29% vs. 23%, P = .07) and larger tumors (33% vs. 21%, P = .02), and were more likely to be diagnosed with oral cavity cancers (38% vs. 25%, P < .001) than non-Asians. Asians were also less likely to receive multimodality therapy than non-Asians (90% vs. 95%, P = .02). Asians were more likely to have never smoked (49% vs. 15%, P < .001) and to be married or with a partner (80% vs. 69%, P = .02). Multivariate models showed that Asians had better OS than non-Asians (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.25-0.99, P = .05). Three-year OS did not differ significantly between Asians and non-Asians (41% vs. 42%, P = .18); however, 5-year OS did (22% vs. 19% P = .03). Stratifying by treatment type, outcomes were comparable in both groups except for radiotherapy alone, where Asians showed significantly better OS (HR = 0.71, 95% CI = 0.51-0.99, P = .04). Advanced age, worse ECOG, greater tumor size, and lack of treatment also correlated with inferior OS.

Conclusions

Despite several worse prognostic features and less aggressive treatment, Asians tended to exhibit better OS than non-Asians.

Level of Evidence

2c. Laryngoscope, 2017

http://ift.tt/2oZSjyg

Head and neck sweat gland adenocarcinoma: A population-based perspective of a rare entity

Objectives

Head and neck sweat gland adenocarcinoma (HNSGA) is an extremely rare malignancy. We present the first population-based analysis regarding this entity.

Study Design

Retrospective population-based analysis.

Methods

Using the Surveillance, Epidemiology, and End Results registry from 2000 to 2013, we extracted 627 cases of HNSGA. Data were analyzed for incidence trends, demographic and clinicopathologic traits, and predictors of disease-specific survival (DSS).

Results

The majority HNSGA cases were white, male, and 60 to 79 years old. The incidence was 0.036 per 100,000 people. Tumors most often presented as localized disease and histological grade II/III. The skin of the face was the most common primary site (43.4%), followed by the scalp and neck (31.6%). Overall 5-, 10-, and 20-year DSS were 94.6%, 89.6%, and 79.8%, respectively. Ethnicity did not affect survival, whereas a younger age at diagnosis and female sex conferred an advantage at 10 years (P = 0.0386) and 5 years (P = 0.0191), respectively. The origin of the HNSGA (apocrine vs. eccrine) did not affect outcomes. Regional and distant disease predicted worse DSS at 5, 10, and 20 years (P = 0.0026, P < 0.001, P < 0.001, respectively). Compared to grade I/II disease, grade III/IV dramatically worsened 5-, 10-, and 20-year DSS (P = 0.0035, P < 0.0001, P = 0.0011, respectively). Scalp and neck HNSGA exhibited the poorest 20-year DSS compared to other primary sites (P = 0.0024).

Conclusion

We present the largest cohort of HNSGA. Significant poor prognostic indicators include older age, higher tumor grade, greater extent of invasion, and primary site of the scalp or neck.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2olwPsQ

Can we use the status of one ear to predict Eustachian tube function of the contralateral ear?

http://ift.tt/2p06UtK

In reference to “Is esophagoscopy necessary during panendoscopy?”

http://ift.tt/2olrulF

Mustervorlage für Hygieneplan

http://ift.tt/2o21L0B

Sterbegeld muss versteuert werden

http://ift.tt/2olSfaZ

Neue Optionen der Teamarbeit in Kommunen

Eine Versorgung chronisch Kranker über alle Sektoren und Betreuungsbereiche hinweg ist in Deutschland meist noch Utopie. Doch mancherorts gibt es Keimzellen für neue Modelle mit Vorbildcharakter.

http://ift.tt/2o23oLM

Bezolds Reisegepäck

Die medizinische Wissenschaft will messen, vergleichen und einordnen. Die ersten Höhepunkte der vergleichenden Hörprüfungen mit mechanischen Instrumenten verdanken wir Friedrich Bezold und seiner „kontinuierlichen Tonreihe", die im Münchener Physikalisch-Mechanischen Institut von Max T. Edelmann ab 1893 gefertigt wurden.

http://ift.tt/2olCCRa

„Es klappt ja doch mit Familie!“

Beruf und Familie – das funktioniert auch in eigener Praxis. Vielleicht sogar besser als im Krankenhaus. Diese Erkenntnis konnten junge Ärzte vom „Tag der Chancen" in Thüringen im März mitnehmen.

http://ift.tt/2o2dqw8

Videosprechstunde darf persönlichen Kontakt nicht ersetzen

Die Videosprechstunde ist auf dem Weg in die Regelversorgung. Jetzt wurden technische Anforderungen veröffentlicht, ab Juli 2017 soll es eine eigene EBM-Ziffer geben. Alles andere als unmissverständlich sind jedoch die berufsrechtlichen Rahmenbedingungen.

http://ift.tt/2o29qvM

Haben Sie auch eine fachliche Frage?

http://ift.tt/2o2cJTB

Ist eine HPV-Impfung bei Rezidiv eines Virus-Typ-16-Papilloms sinnvoll?

http://ift.tt/2olD9m3

Moderne Wiederherstellungschirurgie mit freien Lappen

Moderne Kopf-Hals-Chirurgie wäre ohne die Einführung von freien, mikrovaskulären Transplantaten vor etwa vier Jahrzehnten in der heutigen Form nicht denkbar. Erst dadurch wurde der Verschluss großer Weichteildefekte möglich oder erheblich vereinfacht. Im Folgenden soll insbesondere auf Aspekte der modernen rekonstruktiven Möglichkeiten im Bereich des Pharynx und der Mundhöhle eingegangen werden.

http://ift.tt/2olBjBJ

Was wächst da im Mundboden?

http://ift.tt/2olIPwt

Praxischefs ziehen Lehren aus Online-Bewertungen

Patientenkritik an der Praxis auf Online-Portalen lassen Praxischefs meist nicht kalt. Mehr als die Hälfte hat bereits reagiert, um die Prozesse in ihrem Versorgungsalltag zu optimieren.

http://ift.tt/2o2hWLp

Otitis media: keine verkürzte Antibiose bei Babys

Gute Gründe sprechen einem US-Ärzteteam zufolge gegen die Abkürzung einer antibiotischen Therapie bei Babys mit Otitis media. In der randomisierten, placebokontrollierten Studie schlug die fünftägige Behandlung deutlich schlechter an als das Standardregime über zehn Tage, und die Kinder benötigten letztlich mehr Antibiotika pro Erkältungssaison.

http://ift.tt/2olICcn

Epidermoidzyste

http://ift.tt/2o2ds7e

Inhaltsverzeichnis

http://ift.tt/2olF21P

SLIT: gute Lebensqualität und hohe Adhärenz

Die Adhärenz zu einer Behandlung mit sublingualer Immuntherapie wird umso besser sein, je mehr ein Patient einen Therapieeffekt etwa in Form einer verbesserten Lebensqualität spürt. Eine Praxisstudie liefert Daten zu diesem postulierten Zusammenhang.

http://ift.tt/2o2aQ9y

Larynx- und Hypopharynxkarzinom: Langzeitergebnisse zum Larynxerhalt

In der Studie EORTC 24954 wurden die sequenzielle und die alternierende Radiochemotherapie bei Patienten mit lokal fortgeschrittenem Larynx- und Hypopharynxkarzinom über einen Zeitraum von zehn Jahren verglichen.

http://ift.tt/2olupMu

Vom Umgang mit der Selbstkritik

http://ift.tt/2o2c1G5

ISDN-Abschied ohne Schrecken

2018 soll Schluss sein mit dem ISDN-Netz. Dann wollen die Telekom, 1&1 und andere große Telefonnetzanbieter ihre Leitungen endgültig auf „All-IP" umstellen. Gerade gewerbliche Kunden wie Arztpraxen kann es auch schon früher treffen. Welche Optionen haben Betroffene?

http://ift.tt/2olIObT

Cardiotoxicity with Itraconazole

Itraconazole is a commonly used antifungal drug. In addition to commonly described adverse effects, there have been few reports of heart failure with its use. We present two cases that developed acute systolic heart failure with Itraconazole use. A man in his early 30s was admitted with worsening leg swelling and dyspnoea on exertion. He had been on Itraconazole for blastomyces skin ulcer. His ejection fraction (EF) was found to be 10%–15%. Another man in his 50s was admitted with similar symptoms; his EF was 40%–45%. He had been on Itraconazole for forearm cellulitis. No other aetiology was identified in both patients despite extensive work-up including cardiac catheterisation. Itraconazole was stopped in both the cases. Our first patient did not improve even months after cessation of therapy and was referred for heart transplant. Our second patient improved after a few weeks, and his ejection fraction had improved on repeat testing.

http://ift.tt/2nzlc4K

Comparison of self-reported signs of facial ageing among Caucasian women in Australia versus those in the USA, the UK and Canada

Abstract

Background/Objectives

Australians are more exposed to higher solar UV radiation levels that accelerate signs of facial ageing than individuals who live in temperate northern countries. The severity and course of self-reported facial ageing among fair-skinned Australian women were compared with those living in Canada, the UK and the USA.

Methods

Women voluntarily recruited into a proprietary opt-in survey panel completed an internet-based questionnaire about their facial ageing. Participants aged 18–75 years compared their features against photonumeric rating scales depicting degrees of severity for forehead, crow's feet and glabellar lines, tear troughs, midface volume loss, nasolabial folds, oral commissures and perioral lines. Data from Caucasian and Asian women with Fitzpatrick skin types I–III were analysed by linear regression for the impact of country (Australia versus Canada, the UK and the USA) on ageing severity for each feature, after controlling for age and race.

Results

Among 1472 women, Australians reported higher rates of change and significantly more severe facial lines (P ≤ 0.040) and volume-related features like tear troughs and nasolabial folds (P ≤ 0.03) than women from the other countries. More Australians also reported moderate to severe ageing for all features one to two decades earlier than US women.

Conclusions

Australian women reported more severe signs of facial ageing sooner than other women and volume-related changes up to 20 years earlier than those in the USA, which may suggest that environmental factors also impact volume-related ageing. These findings have implications for managing their facial aesthetic concerns.

http://ift.tt/2otEesf

What Is the “Screening Effect” Six Years After the Fukushima Nuclear Power Plant Accident?

Thyroid , Vol. 0, No. 0.


http://ift.tt/2nXfGUR

Zukunft jetzt − Implementierung eines IT-gestützten Distress-Screenings

Zusammenfassung

Hintergrund

Eine bedarfsgerechte integrierte Mitbehandlung psychischer Belastungen und Störungen gehört zu den Herausforderungen einer modernen Krebsmedizin. Ohne standardmäßiges Screening auf psychischen Distress bleibt ein großer Teil der versorgungsbedürftigen Krebspatienten unerkannt. Mit der verpflichtenden Einführung von Distress-Screenings in die onkologische Routineversorgung entsteht für die deutschen Krebszentren ein erhöhter Dokumentationsaufwand. IT-gestützte Screening-Prozeduren können diesen kompensieren. Während die S3-Leitlinie Psychoonkologie Methoden und strukturelle Maßnahmen zur fachkundigen Umsetzung eines standardgemäßen Screenings beschreibt, fehlen bisher Handlungsempfehlungen zur Implementierung eines IT-gestützten Distress-Screenings.

Methoden

Es wurde ein Konsensusmeeting „IT-gestütztes Distress-Screening in der onkologischen Routineversorgung" durchgeführt.

Ergebnisse

Es wurden Konsensempfehlungen zur Implementierung und Nutzung IT-gestützter Distress-Screenings ausgearbeitet. Diese beziehen sich auf: 1) Vorbereitung der Implementierung, 2) IT-Ausstattung, 3) Implementierung, 4) Praktische Nutzung, 5) Qualitätssichernde Maßnahmen im Forschungskontext. Ausgewählte deutschsprachige Forschungsprojekte und aktuelle Entwicklungen in der klinischen Versorgungsforschung unterstreichen, welches Potenzial in der Zusammenführung von klinischer Expertise mit der Informationstechnologie steckt.

Schlussfolgerungen

Mit den Ergebnissen des Konsensusmeetings stehen nun ein Leitfaden und Kriterienkatalog für die Implementierung eines IT-basierten Distress-Screenings in der onkologischen Routineversorgung zur Verfügung. Die Umsetzung dieser Empfehlungen kann die Versorgungsqualität von Krebspatienten in Deutschland verbessern.

http://ift.tt/2oZKHJg

Specific blaCTX-M-8/IncI1 Plasmid Transfer among Genetically Diverse Escherichia coli across Humans and Chickens [PublishAheadOfPrint]

We investigated the genetic backbones of 14 bla_CTX-M-8-positive Escherichia coli isolates recovered from human stools and chicken meat. All isolates carried IncI1 plasmids with bla_CTX-M-8 (bla_CTX-M-8/IncI1), and most (9/14) belonged to a specific genetic lineage, namely, plasmid sequence type (pST) 113. The genetic contexts of the 9 bla_CTX-M-8/IncI1-pST113 were similar, regardless of the source. These results suggest probable local transfer of the bla_CTX-M-8/IncI1 between humans and chicken with genetically diverse E. coli.

http://ift.tt/2nzbI9v

Synthetic (p)ppGpp analogue: Inhibitor of stringent response in mycobacteria [PublishAheadOfPrint]

Bacteria elicit an adaptive response against hostile conditions such as starvation and other kind of stresses. Their ability to survive such conditions depends on, in part, stringent response pathways. (p)ppGpp, considered to be the master regulator of stringent response, is a novel target for inhibiting the survival of the bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for its stress response and persistence inside the host. Our aim was to design an inhibitor of (p)ppGpp synthesis, follow efficiency through enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and NMR spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by Rel_Msm in the presence of designed inhibitors in a dose dependent manner, which we further confirmed by following the enzyme kinetics. The Rel enzyme-inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long term persistence, biofilm formation and biofilm disruption were assayed in Mycobacterium smegmatis, where inhibition in each case was observed. In-vivo (p)ppGpp levels were found to be down-regulated in M. smegmatis treated with the synthetic inhibitors. Compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis. The compounds were tested for toxicity by MTT assay using H460 cells and hemolysis assay using Human RBCs, for which they were found to be non-toxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry.

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Click chemistry-facilitated structural diversification of nitrothiazoles, nitrofurans and nitropyrroles enhances antimicrobial activity against Giardia lamblia [PublishAheadOfPrint]

Giardia lamblia is an important and ubiquitous cause of diarrheal disease. The primary agents in the treatment of giardiasis are nitroheterocyclic drugs, particularly the imidazoles metronidazole and tinidazole, and the thiazole, nitazoxanide. Although these drugs are generally effective, treatment failures occur in up to 20% of cases and resistance has been demonstrated in vivo and in vitro. Prior work had suggested that side chain modifications of the imidazole core can lead to effective new 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has not been systematically investigated as an antimicrobial drug scaffold. Click chemistry was employed to synthesize 442 novel nitroheterocyclic compounds with extensive side chain modifications. Screening of this library against representative G. lamblia strains showed a wide spectrum of in vitro activities, with many of the compounds exhibiting superior activity relative to reference drugs and several showing >100-fold increase in potency and the ability to overcome existing forms of metronidazole resistance. The majority of new compounds displayed no cytotoxicity against human cells, and several of them were orally active against murine giardiasis in vivo. These findings provide additional impetus for the systematic development of nitroheterocyclic compounds with non-imidazole cores as alternative and improved agents for the treatment of giardiasis and potentially other infectious agents.

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A Topical Hydrogel With Deferiprone and Gallium-Protoporphyrin Targets Bacterial Iron Metabolism and Has Antibiofilm Activity [PublishAheadOfPrint]

Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. Whilst oral drug-delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection-site while reducing systemic side-effects.

This study determined the antibiofilm activity of a surgical wound-gel loaded with the iron-chelator deferiprone (Def) and the heme-analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. The activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of colony forming units and correlative light/electron microscopy.

While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gel (log10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for a significant activity against P.aeruginosa biofilms (log10 reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds.

Def-GaPP delivered in a surgical wound-gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for a clinical utilization as therapy for topical biofilm-related infections.

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ETHAMBUTOL IS CLEARED BY A CONTEMPORARY HIGH-FLUX HEMODIALYZER, AND DRUG MONITORING ENSURES SAFETY AND THERAPEUTICITY [PublishAheadOfPrint]

It is uncertain, given the lack of recent data and the inconclusive nature of previous data, whether ethambutol is cleared by hemodialysis using contemporary dialyzers. We measured serum ethambutol concentrations before, during and one hour after hemodialysis in a 75-year-old Caucasian male receiving ethambutol for disseminated Bacille Calmette-Guérin infection. There was a mean 41% decrease in serum ethambutol concentration during dialysis, confirming the hemodialyzability of ethambutol and the utility of drug monitoring in ensuring safety.

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Salicylidene acylhydrazides and hydroxyquinolines act as inhibitors of type three secretion systems in Pseudomonas aeruginosa by distinct mechanisms. [PublishAheadOfPrint]

Type three secretion systems (T3SS) are major virulence factors in Gram-negative bacteria. Pseudomonas aeruginosa expresses two T3SS, namely an injectisome (iT3SS) translocating effector proteins in the host cell cytosol, and a flagellum (fT3SS) insuring bacterial motility. Inhibiting these systems is an appealing therapeutic strategy for acute infections. This study examines the protective effects of the salicylidene acylhydrazide INP0341 and of the hydroxyquinoline INP1750 (previously described as T3SS inhibitors in other species) towards cytotoxic effects of P. aeruginosa in vitro. Both compounds reduced cell necrosis and inflammasome activation induced by reference strains or clinical isolates expressing T3SS toxins or only the translocation apparatus. INP0341 inhibited iT3SS transcriptional activation, including in strains with constitutive iT3SS expression, and reduced the total expression of toxins, suggesting it targets iT3SS gene transcription. INP1750 inhibited toxin secretion and flagellar motility and impaired the activity the YscN ATPase from Yersinia pseudotuberculosis (homologous to the ATPase present in the basal body of P. aeruginosa iT3SS and fT3SS), suggesting it rather targets a T3SS core constituent with high homology among iT3SS and fT3SS. This mode of action is similar to that previously described for INP1855, another hydroxyquinoline, against P. aeruginosa. Thus, although acting by different mechanisms, INP0341 and INP1750 appear as useful inhibitors of the virulence of P. aeruginosa. Hydroxyquinolines may have a broader spectrum of activity by the fact they act upon two virulence factors (iT3SS and fT3SS).

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Rifabutin Is Active Against Mycobacterium abscessus Complex [PublishAheadOfPrint]

Lung infections with Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and other patient groups. Recent evidence for human-to-human transmission worsens the situation. M. abscessus is an intrinsically multidrug resistant pathogen showing resistance even against standard anti tuberculosis drugs such as rifampicin. Here, our objective was to identify existing drugs that may be employed for the treatment of M. abscessus lung disease. A collection of more than 2700 approved drugs was screened at a single point concentration against an M. abscessus clinical isolate. Hits were confirmed with fresh solids in dose response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three M. abscessus subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampicin derivative rifabutin had an MIC of 3 ± 2 μM (3 μg/mL) against the screening strain, the reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T and M. abscesuss subsp. massiliense CCUG 48898-T, as well as a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin resistant strains. In conclusion, rifabutin - in contrast to rifampicin - is active against the Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.

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In vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against E. coli, K. pneumoniae, and P. aeruginosa [PublishAheadOfPrint]

Fosfomycin is a broad-spectrum agent with activity against gram-positive and gram-negative bacteria, including drug-resistant strains, such as extended spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) gram-negative rods. In the present study, the pharmacokinetic/pharmacodynamic (PK/PD) activity of ZTI-01 (fosfomycin for injection) was evaluated in the neutropenic murine thigh infection model against 5 E. coli (EC), 3 K. pneumoniae (KPN), and 2 P. aeruginosa (PSA) strains, including a subset with ESBL and CR phenotype. The pharmacokinetics of ZTI-01 were examined in mice after subcutaneous administration of 3.125, 12.5, 50, 200, 400 and 800 mg/kg. The half-life ranged from 0.51 to 1.1 h, area under the concentration-time curve (AUC_0-) ranged from 1.4 to 87 mg*h/L, and maximum concentrations ranged from 0.6 to 42.4 mg/L. Dose fractionation demonstrated AUC/MIC ratio to be the PK/PD index most closely linked to efficacy (R² = 0.70). Net stasis and cidal activity was observed against all strains. Net stasis was observed at 24 h AUC/MIC values of 24, 21, and 15 for EC, KPN and PSA, respectively. For the Enterobacteriaceae group stasis was noted at mean 24 h AUC/MIC targets of 23 and 1 log kill at 83. Survival in mice infected with EC 145 was maximal at 24 h AUC/MIC exposures of 9-43, which is comparable to the stasis exposures identified in the PK/PD studies. These results should prove useful for the design of clinical dosing regimens for ZTI-01 in the treatment of serious infections due to Enterobacteriaceae and Pseudomonas.

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Klebsiella pneumoniae ST11 and ST147 highly resistant to tigecycline from companion animals [PublishAheadOfPrint]

In this study we have characterized two tigecycline resistant Klebsiella pneumoniae clones isolated from dog urine samples. The isolates were genetically unrelated, belonging to sequence types ST11 and ST147, both classically related to human isolates. To the best of our knowledge, this is the first identification of tigecycline resistant isolates from animals. We unveil the worrisome circulation among animals of bacterial clones resistant to this last resort antibiotic.

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Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex that Confer Multi-Nucleoside Drug Resistance [PublishAheadOfPrint]

HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations emerge that confer resistance to nucleoside RT inhibitors (NRTIs) in clinical use. Q151M, and four associated mutations A62V, V75I, F77L, and F116Y were detected in patients failing therapies to dideoxynucleosides (didanosine, ddI; zalcitabine, ddC) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we have systematically determined crystal structures of wild-type RT/dsDNA/dATP (I), wild-type RT/dsDNA/ddATP (II), Q151M RT/dsDNA/dATP (III), Q151Mc RT/dsDNA/dATP (IV), and Q151Mc RT/dsDNA/ddATP (V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3' -endo and 3' -exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the dNTP-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side-chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed, and has a switched conformation for the key conserved residue R72 compared to that in wtRT. Based on a modeled structure of hepatitis B (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.

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Resistance to ceftazidime-avibactam in Klebsiella pneumoniae due to porin mutations and the increased expression of KPC-3 [PublishAheadOfPrint]

We reported the first clinical case of a ceftazidime-avibactam resistant KPC-3-producing Klebsiella pneumoniae (1), from a patient with no prior history of ceftazidime-avibactam therapy....

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Antibiotic Resistance Markers in Strain Bp1651 of Burkholderia pseudomallei Identified by Genome Sequence Analysis. [PublishAheadOfPrint]

Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis including β-lactams such as penicillins (amoxicillin/clavulanic acid), cephalosporins (ceftazidime), carbapenems (imipenem and meropenem), as well as tetracyclines and sulfonamides. We sequenced, assembled, and annotated the Bp1651 genome, and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance, and T147A contributed to amoxicillin/clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei. Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely due to a frame shift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis.

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Lymph Node Central Necrosis on the Computed Tomography as the Predictor of the Extra Capsular Spread in Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

The aim of this study is to investigate the relationship between the presence of the cervical lymph node with central necrosis as on the preoperative imaging and postoperative histopathological identification of the lymph node extra capsular spread. This study is a prospective study conducted at J.L.N. Hospital and Research Centre, Bhilai (C.G), from August 2011 to January 2014. Thirty patients with metastatic head and neck squamous cell carcinoma were enrolled. All candidates were subjected to a detailed history taking and clinical examination. Their preoperative computed tomography (CT) scans were assessed with attention to the presence and absence of lymph node, lymph node size, shape, level, presence or absence of the lymph node central necrosis and other signs of the ECS such as thick walled enhancing nodal margin, loss of margin definition, alteration of adjacent fat planes. These patients then underwent surgery which included resection of the primary with the neck dissection. The preoperative records of the lymph node size and location were observed radio-graphically and analyzed with the resected lymph node histopathologically. These data was used for finding out correlation. Of the total 30 patients studied, 24 patients were male and 6 patients female with ratio of 4:1. The most common group of the patients were of malignancy of gingivobuccal sulcus. Out of the 30 patients 19 patients had the radiographic evidence of the central necrosis, out of which 11 had the extra capsular spread on the histological analysis. In no patients did we found histopathology extra capsular spread without central necrosis. Thus the central necrosis on the CT has the high sensitivity for detection of the extra capsular spread. Out of the 19 lymph node without extra capsular spread, 11 lymph nodes had no central necrosis on the preoperative CT, remaining 8 lymph node were having central necrosis on CT whereas post op histopathology of these 8 lymph nodes showed metastatic deposit, indicating the low specificity of the central necrosis in detection of the ECS. Lymph node central necrosis on pre-operative CT is sensitive indicator with a high negative predictive value for lymph node extra capsular spread. Future studies focusing on identifying molecular mediator involved in ECS to determine targets for adjuvant therapies in this subset of patients are recommended.

http://ift.tt/2ojaldG

Septorhinoplasty: Our Experience

Abstract

Rhinoplasty is one of the oldest known surgeries to the human kind. However, being a cosmetic of surgery of utmost importance, it has been an attractive and fascinating surgery for the otolaryngologists and plastic surgeons. Along with the evolution of improved techniques and better surgical modalities, this surgery has been growing in panorama including its indications, needs and techniques. We present our experience with rhinoplasty in a tertiary care center of north India. We have included all cases operated with septorhinoplasty from 2001 to 2014 by the senior author in the manuscript. We reviewed their presentations, investigations, preoperative counselling records, operative details and post-operative clinical records to audit our results and hence to document our experiences in septorhinoplasties. A total of 53 cases including 37 males and 16 females had undergone rhinoplasty surgeries. The most common reason of disfigurement was road traffic accident (58.5%). All these patients included different deformities and required varied corrections. There were no major post-operative complications except persistent edema with longest lasting for 23 weeks. Thermal splints gave a better patient satisfaction in post-op compared to POP splints. Results were completely and partially satisfying for 50 patients and not satisfying for three. Unrealistic expectations from the procedure might be the reason for non-satisfactory results in rhinoplasty. Rhinoplasty is a delicate procedure and has greater aesthetic implications in planning surgical techniques and approaches. For better satisfaction of patients, adequate preoperative counseling and realistic expectations are warranted. Skillful surgical techniques null chances of complications.

http://ift.tt/2oZaSQk

Kontaktallergien der Kopfhaut

Zusammenfassung

Kontaktallergien der Kopfhaut stellen eine wichtige Differenzialdiagnose von Kopfhauterkrankungen dar. Die typischen Effloreszenzen bekräftigen zusammen mit Streuherden, Juckreiz und Anamnese die Verdachtsdiagnose. Da die behaarte Kopfhaut eher unempfindlich gegenüber einer Kontaktdermatitis ist, verursachen hier applizierte Allergene oft Reaktionen um Augen, Ohren und Hals. Potente Allergene, wie z. B. para-Phenylendiamin, können aber durchaus auch auf der behaarten Kopfhaut starke Reaktionen auslösen. Die häufigsten für die Kopfhaut relevanten Allergene finden sich in Haarfarben und Bleichmitteln, Shampoos und Haarspülungen, Produkten für Dauerwelle und Haarglättung sowie in topischen Medikamenten. Neben den aktiven Wirkstoffen sind Vehikel und Konservierungsmittel häufige auslösende Allergene. Mittels topischer Steroide und oraler Antihistaminika kommt es rasch zur Abheilung, nur bei schweren Reaktionen werden systemische Steroide benötigt. Eine adäquate Epikutantestung mittels vorhandener Testreihen, kombiniert mit den Inhaltsstoffen patienteneigener Produkte, bekräftigt oder widerlegt die Diagnose und ermöglicht die Allergenkarenz sowie die Auswahl geeigneter Ersatzprodukte.

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Dexamethasone for nerve blocks: Design matters!

With a few notable exceptions, efforts to prolong peripheral nerve blocks with adjuvant drugs have been generally disappointing. One prime exception is dexamethasone: it has been demonstrated to prolong analgesia as well as sensory and motor block in multiple contexts, although numbers are too low to make definitive statements about safety [1]. All the early studies, however, assumed the action of dexamethasone was on the peripheral nerve and therefore did not include systemic controls. Desmet and colleagues upset the apple cart in 2013 with their report that 10mg of systemic dexamethasone appears to prolong the time to first analgesic request as much as perineural administration [2].

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Occupational stress of anesthesia: Effects on aging

Anesthesiology has been identified as a stressful specialty. Chronic psychological stress may lead to biological aging and skin aging.

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Labetalol, nitroglycerin, controlled hypotension, sinus endoscopic surgery

To assess the efficacy of labetalol versus nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery.

http://ift.tt/2p0khaz

Effective sparsity control in deep belief networks using normal regularization term

Abstract

Nowadays the use of deep network architectures has become widespread in machine learning. Deep belief networks (DBNs) have deep network architectures to create a powerful generative model using training data. Deep belief networks can be used in classification and feature learning. A DBN can be learned unsupervised, and then the learned features are suitable for a simple classifier (like a linear classifier) with a few labeled data. In addition, according to researches, by using sparsity in DBNs we can learn useful low-level feature representations for unlabeled data. In sparse representation, we have the property that learned features can be interpreted, i.e., correspond to meaningful aspects of the input, and capture factors of variation in the data. Different methods are proposed to build sparse DBNs. In this paper, we proposed a new method that has different behavior according to deviation of the activation of the hidden units from a (low) fixed value. In addition, our proposed regularization term has a variance parameter that can control the force degree of sparseness. According to the results, our new method achieves the best recognition accuracy on the test sets in different datasets with different applications (image, speech and text) and we can achieve incredible results when using a different number of training samples, especially when we have a few samples for training.

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Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients

Summary

Little is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed. Body mass index (BMI; kg/m²) and muscle mass using CT were measured prior to treatment initiation. Chi-squared test and Mann-Whitney's tests were used for the comparison of categorical and continuous variables respectively. Among 68 melanoma patients treated with anti-PD1 (47 pembrolizumab, 21 nivolumab), 38 (56%) patients had a BMI ≥ 25 kg/m² and 11 (16%) a BMI ≥ 30, while 13 (19%) had both sarcopenia and a BMI ≥ 25 kg/m². For the 11 (16%) patients who experienced early ALT, the mean BMI was higher (27.9 versus 24.7 kg/m²; p = 0.04). Among the 32 female patients, sarcopenic overweight patients had a 6.5-fold increased risk of ALT (50 versus 7.7%; p = 0.01). Sarcopenic overweight is associated with more early ALT of anti-PD1 in melanoma patients.

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Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results

Abstract

Purpose

The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE).

Methods

In 14 TS (mean age 13.8), LE (17β-estradiol, 62.5 μg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17β-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed.

Results

There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17β-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 μIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group.

Conclusion

Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

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Validation of the Italian Quality of Life in Short Stature Youth (QoLISSY) questionnaire

Abstract

Purpose

The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation.

Methods

Focus group discussions and a cognitive debriefing process with children (N = 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (N = 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (N = 32).

Results

The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity.

Conclusion

In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.

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Quality of life after thyroid surgery

Abstract

Purpose

The purpose of this study was to inquire how patients' quality of life is affected after thyroid surgery and the factors involved.

Methods

A semi-structured questionnaire and the World Health Organization Quality of Life Scale (WHOQOL-BREF) were applied to 101 patients prior to surgery. Thereafter data was collected in the early and again in the late post-operative period.

Results

Mean general health score for pre-operative quality of life was 6.72 ± 1.53 (3–10), mean physical field score was 22.81 ± 2.77 (17–31), mean psychological field score was 21.69 ± 2.78 (15–28), mean social field score was 11.10 ± 1.94 (5–15) and mean environmental field score was 27.86 ± 4.30 (18–39). In the early post-operative period, mean general health score was 7.05 ± 1.45 (4–10), mean physical field score was 22.84 ± 2.83 (14–29), mean psychological field score was 21.67 ± 2.32 (16–27), mean social field score was 10.89 ± 1.96 (5–15) and mean environmental field score was 28.56 ± 4.18 (18–40). In the late post-operative period, the general health score for quality of life was 7.43 ± 1.34 (4–10), mean physical field score was 23.59 ± 2.70 (17–35), mean psychological field score was 21.75 ± 2.34 (14–29), mean social field score was 11.23 ± 1.94 (6–15) and mean on-field environment score was 29.30 ± 3.96 (16–40). The pre-operative levels of symptoms were found to be higher than early and late post-operative periods.

Conclusions

Quality of life increased after total thyroidectomy and statistically significant improvement was observed in late post-operative stage.

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Elevated levels of TL1A are associated with disease activity in patients with systemic sclerosis

Abstract

TL1A is a member of the TNF superfamily. It performs significantly in the pathogenesis of rheumatic and autoimmune diseases partly through regulating the Th17 pathway. The clinical implication of circulating TL1A in patients with systemic sclerosis (SSc) remains unclear, and correlation between TL1A and Th17-related cytokines in the pathogenesis of SSc needs to be discussed. We measured serum levels of TL1A and Th17-related cytokines by ELISA in 47 patients with SSc, 56 patients with SLE, and 53 healthy subjects, and investigated association of these cytokines with clinical manifestations and laboratory variables. TL1A in relation to Th17-related cytokines were examined. In addition, the transcript level of TL1A in peripheral blood mononuclear cells (PBMCs) was determined by real-time reverse transcription polymerase chain reaction (real-time PCR). Serum TL1A levels were higher in patients with SSc than in healthy controls (P = 0.001), but were lower compared with SLE patients (P = 0.004). Diffuse cutaneous SSc or limited cutaneous SSc patients reported elevated expression of TL1A than those in healthy controls (P = 0.002, P = 0.007). Patients with active disease showed significantly higher expression of TL1A when compared with less active disease (P = 0.014). SSc patients with arthritis, elevated IgG titer, ESR >30 mm/h, and CRP >5 mg/l displayed elevated expression of TL1A, respectively. Serum levels of IL-17 and IL-21 were increased in SSc patients compared with healthy controls and positively related to TL1A levels (r _s = 0.373, P = 0.010; r _s = 0.370, P = 0.011, respectively). Moreover, TL1A mRNA expression in PBMCs was significantly higher in patients with SSc compared with healthy controls (P < 0.001). TL1A may play a role in the development of SSc.

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Multidisciplinary team approach to traumatic spinal cord injuries: a single institution’s quality improvement project

Abstract

Background

A stepwise multidisciplinary team (MDT) approach to the injured trauma patient has been reported to have an overall benefit, with reduction in mortality and improved morbidity. Based on clinical experience, we hypothesized that implementation of a dedicated Spinal Cord Injury Service (SCIS) would impact outcomes of a patient specific population on the trauma service.

Methods

The trauma center registry was retrospectively queried, from January 2011 through December 2015, for patients presenting with a spinal cord injury. In 2013, a twice weekly rounding SCIS MDT was initiated. This new multidisciplinary service, the post-SCIS, was compared to the 2011–2012 pre-SCIS. The two groups were compared across patient demographics, mechanism of injury, surgical procedures, and disposition at discharge. The primary outcome was mortality. Secondary endpoints also included the incidence of complications, hospital length of stay (HLOS), ICU LOS, ventilator free days, and all hospital-acquired infectious complications. Logistic regression and Student's t test were used to analyze data.

Results

Ninety-five patients were identified. Of these patients, 41 (43%) pre-SCIS and 54 (57%) post-SCIS patients were compared. Mean age was 46.9 years and 79% male. Overall, adjusted mortality rate between the two groups was significant with the implementation of the post-SCIS (p = 0.033). In comparison, the post-SCIS revealed shorter HLOS (23 vs 34.8 days, p = 0.004), increased ventilator free days (20.2 vs 63.3 days, p < 0.001), and less nosocomial infections (1.8 vs 22%, p = 0.002). While the post-SCIS mean ICU LOS was shorter (12 vs 17.9 days, p = 0.089), this relationship was not significant.

Conclusions

The application of an SCIS team in addition to the trauma service suggests that a structured coordinated approach can have an expected improvement in hospital outcomes and shorter length of stays. We believe that this clinical collaboration provides distinct specialist perspectives and, therefore, optimizes quality improvement.

Level of evidence Epidemiologic study, level III.

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Effects of Early Smoking Habits on Young Adult Female Voices in Greece

Publication date: Available online 10 April 2017
Source:Journal of Voice
Author(s): Dionysios Tafiadis, Eugenia I. Toki, Kevin J. Miller, Nausica Ziavra
Cigarette use is a preventable cause of mortality and diseases. The World Health Organization states that Europe and especially Greece has the highest occurrence of smoking among adults. The prevalence of smoking among women in Greece was estimated to be over 30% in 2012. Smoking is a risk factor for many diseases. Studies have demonstrated the association between smoking and laryngeal pathologies as well as changes in voice characteristics. The purpose of this study was to estimate the effect of early smoking habit on young adult female voices and if they perceive any vocal changes using two assessment methods. The Voice Handicap Index and the acoustic analyses of voice measurements were used, with both serving as mini-assessment protocols. Two hundred and ten young females (110 smokers and 100 nonsmokers) attending the Technological Educational Institute of Epirus in the School of Health and Welfare were included. Statistically significant increases for physical and total scores of the Voice Handicap Index were found in the smokers group (P < 0.05). Significant changes were observed for the acoustic parameters between smoker and nonsmoker groups. The results of this study indicated observable signs of change in the voice acoustic characteristics of young adults with early smoking habits.



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Crura augmentation with Bio-A ® mesh for laparoscopic repair of hiatal hernia: single-institution experience with 100 consecutive patients

Abstract

Background

The potential utility of both non-absorbable and absorbable meshes to reinforce the esophageal hiatus and prevent recurrent hernia has been investigated in observational studies and a few randomized clinical trials. Use of absorbable mesh has been associated with lesser side-effects, but the long-term safety and effectiveness are still debated. This rather scanty clinical evidence is due to heterogeneity and bias regarding the type of mesh and operation used, the modalities of follow-up, and the reporting of objective results.

Objectives

The aim of the study was to assess safety, quality of life, and recurrence-free probability after laparoscopic repair of hiatal hernia reinforced with a synthetic absorbable mesh.

Methods

Observational, retrospective, single-center cohort study. All patients with hiatal hernia who underwent laparoscopic crura repair using a biosynthetic mesh (Gore Bio A^® tissue reinforcement, Flagstaff, AZ) were included. Pre- and post-operative symptoms were assessed with the GERD-HRQL questionnaire. Objective follow-up consisted of upper gastrointestinal endoscopy and barium swallow study.

Results

From September 2011 to March 2016, a total of 100 patients underwent hiatal hernia repair using a Bio-A^® mesh. All surgical procedures were completed laparoscopically. Postoperative morbidity rate was 10%. All patients had a minimum follow-up of 6 months, and the median follow-up was 30 (IQR = 22) months. No mesh-related complications occurred. The incidence of recurrent hernia ≥2 cm was 9%, and eight of the nine patients had a preoperative type III hernia. The median GERD-HRQL score was significantly reduced after operation (p < 0.001). The recurrence-free probability at 1 and 5 years was, respectively, 0.99 (CI 0.97–1.00) and 0.84 (CI 0.74–0.97), and no reoperation was required. No association was found between age, BMI, hernia size, previously failed surgical repairs and hernia recurrence.

Conclusions

The use of a synthetic absorbable mesh to reinforce the esophageal hiatus is safe and appears to be effective and durable over a medium-term follow-up.

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The activity of selective sigma-1 receptor ligands in seizure models in vivo

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Edijs Vavers, Baiba Svalbe, Lasma Lauberte, Ilmars Stonans, Ilga Misane, Maija Dambrova, Liga Zvejniece
Sigma-1 receptor (Sig1R) is a ligand-regulated protein which, since its discovery, has been widely studied as a novel target to treat neurological disorders, including seizures. However, the roles and mechanisms of Sig1R in the regulation of seizures are not fully understood. The aim of the present study was to test and compare effects of often used selective Sig1R ligands in models of experimentally induced seizures. The anti-seizure activities and interactions of selective Sig1R agonist PRE-084, selective Sig1R antagonist NE-100 and novel positive allosteric Sig1R modulator E1R were evaluated in pentylenetetrazol (PTZ) and (+)-bicuculline (BIC)-induced seizure models in mice.Sig1R antagonist NE-100 at a dose of 25mg/kg demonstrated pro-convulsive activity on PTZ-induced seizures. Agonist PRE-084 did not change the thresholds of chemoconvulsant-induced seizures. Positive allosteric modulator E1R at a dose of 50mg/kg showed anti-convulsive effects on PTZ- and BIC-induced clonic and tonic seizures. The anti-seizure activity of E1R was blocked by NE-100. Surprisingly, NE-100 at a dose of 50mg/kg induced convulsions, but E1R significantly alleviated the convulsive behaviour induced by NE-100.In conclusion, the selective Sig1R antagonist NE-100 induced seizures that could be partially attenuated by positive allosteric Sig1R modulator. Our results confirm that Sig1R could be a novel molecular target for new anti-convulsive drugs.



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Dissociable effects of systemic and orbitofrontal administration of adrenoceptor antagonists on yohimbine-induced motor impulsivity

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Wendy K. Adams, Michael M. Barrus, Fiona D. Zeeb, Paul J. Cocker, James Benoit, Catharine A. Winstanley
The α2-adrenoceptor antagonist, yohimbine, is commonly used as a pharmacological stressor. Its behavioural effects are typically attributed to elevated noradrenaline release via blockade of central, inhibitory autoreceptors. We have previously reported that yohimbine increases motor impulsivity in rats on the five-choice serial reaction time task (5CSRTT), a cognitive behavioural assessment which measures motor impulsivity and visuospatial attention. Furthermore, this effect depended on cyclic adenomonophosphate (cAMP) signalling via cAMP response element binding (CREB) protein in the orbitofrontal cortex (OFC). However, the role of specific adrenoceptors in this effect is not well-characterised. We therefore investigated whether the pro-impulsive effects of systemic yohimbine could be reproduced by direct administration into the OFC, or attenuated by intra-OFC or systemic administration of prazosin and propranolol—antagonists at the α1- and β-adrenoceptor, respectively. Male Long-Evans rats were trained on the 5CSRTT and implanted with guide cannulae aimed at the OFC. Systemically administered α1- or β-adrenoceptor antagonists attenuated yohimbine-induced increases in premature responding. In contrast, local infusion of yohimbine into the OFC reduced such impulsive responding, while blockade of α1- or β-adrenoceptors within the OFC had no effect on either basal or yohimbine-stimulated motor impulsivity. Direct administration of selective antagonists at the α1-, α2- or β-adrenoceptor into the OFC therefore produce clearly dissociable effects from systemic administration. Collectively, these data suggest that the pro-impulsivity effect of yohimbine can be modulated by adrenergic signalling in brain areas outside of the OFC, in addition to non-adrenergic signalling pathways within the OFC.



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Recognition memory-induced gene expression in the perirhinal cortex: A transcriptomic analysis

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Hannah Scott, Mark F. Rogers, Helen L. Scott, Colin Campbell, Elizabeth C. Warburton, James B. Uney
We have used transcriptome analysis to identify genes and pathways that are activated during recognition memory formation in the perirhinal cortex. Rats were exposed to objects either repeatedly, so that the objects become familiar, or to novel objects in a bow-tie maze over six consecutive days. On the final day, one hour after the last exposure to the series of objects, RNA from the perirhinal cortex was sequenced to compare the transcriptome of naïve control rats and rats exposed to either novel or familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats. These included genes coding for transcription factors, GDNF receptors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups, which suggests that this post-transcriptional mechanism may play a role in the consolidation of object recognition memory. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures.



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Chronic social stress leads to altered sleep homeostasis in mice

Publication date: 1 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 327
Author(s): Nadja Olini, Iru Rothfuchs, Damiano Azzinnari, Christopher R. Pryce, Salome Kurth, Reto Huber
Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1–4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression.



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Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Yaminah D. Gilles, Eva K. Polston
Social isolation is a known stressor that negatively impacts the well-being of social species. In rodents, social deprivation experienced either before or after weaning profoundly impacts adult behavioral and neuroendocrine profiles. This study compared the effects of post-natal and post-weaning social deprivation on behavioral profiles and hypothalamic oxytocin (OT) neurons. Male and female Sprague–Dawley rats were assigned to two post-natal groups, maternally separated (MS) or non-MS. MS pups were separated from their mothers for 4h daily during post-natal days 2–21 while non-MS litters remained undisturbed. Animals were then weaned and assigned to single or group housing conditions (SH/GH). Social behaviors were evaluated two weeks later and at 2–3 months of age, depressive-like behavioral profiles were assessed using the forced swim and sucrose preference tests. Animals were euthanized, and hypothalamic OT neurons were quantified. Post-weaning isolation significantly impacted behavioral profiles, with SH animals displaying more social behaviors than GH animals. SH animals also exhibited more immobility behavior in the forced swim test and a decreased sucrose preference. Effects of sex and MS were relatively limited. Correlation analyses revealed an inverse relationship between the display of antagonistic social behaviors and the numbers of OT cells in the anterior parvicellular division of the paraventricular nucleus (PVNap). There were no correlations between numbers of OT neurons and prosocial or depressive-like behaviors. Our results demonstrate a rapid and persistent disruption of behaviors in SH animals and suggest that some of these effects may be associated with numbers of OT neurons in the PVNap.



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Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients

Summary

Little is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed. Body mass index (BMI; kg/m²) and muscle mass using CT were measured prior to treatment initiation. Chi-squared test and Mann-Whitney's tests were used for the comparison of categorical and continuous variables respectively. Among 68 melanoma patients treated with anti-PD1 (47 pembrolizumab, 21 nivolumab), 38 (56%) patients had a BMI ≥ 25 kg/m² and 11 (16%) a BMI ≥ 30, while 13 (19%) had both sarcopenia and a BMI ≥ 25 kg/m². For the 11 (16%) patients who experienced early ALT, the mean BMI was higher (27.9 versus 24.7 kg/m²; p = 0.04). Among the 32 female patients, sarcopenic overweight patients had a 6.5-fold increased risk of ALT (50 versus 7.7%; p = 0.01). Sarcopenic overweight is associated with more early ALT of anti-PD1 in melanoma patients.

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MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1

Abstract

Purpose

The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively.

Results

MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3′UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05).

Conclusions

Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

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High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Bruna C. Favoretto, Adriana A.C. Casabuono, José A. Portes-Junior, Jacqueline F. Jacysyn, Alicia S. Couto, Eliana L. Faquim-Mauro
Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.



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Longevity of metal-ceramic crowns cemented with self-adhesive resin cement: a prospective clinical study

Abstract Resin cements are often used for single crown cementation due to their physical properties. Self-adhesive resin cements gained widespread due to their simplified technique compared to regular resin cement. However, there is lacking clinical evidence about the long-term behavior of this material. The aim of this prospective clinical trial was to assess the survival rates of metal-ceramic crowns cemented with self-adhesive resin cement up to six years. One hundred and twenty-nine subjects received 152 metal-ceramic crowns. The cementation procedures were standardized and performed by previously trained operators. The crowns were assessed as to primary outcome (debonding) and FDI criteria. Statistical analysis was performed using Kaplan-Meier statistics and descriptive analysis. Three failures occurred (debonding), resulting in a 97.6% survival rate. FDI criteria assessment resulted in scores 1 and 2 (acceptable clinical evaluation) for all surviving crowns. The use of self-adhesive resin cement is a feasible alternative for metal-ceramic crowns cementation, achieving high and adequate survival rates.

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Dental Management Survey Brazil (DMS-BR): creation and validation of a management instrument

Abstract Questionnaires for the assessment of knowledge and self-perception can be useful to diagnose what a dentist knows about management and administration. The aim of the present study was to create and validate the Dental Management Survey Brazil (DMS-BR) scale, based on meetings with experts in the field. After having elaborated the first version, 10 audits were performed in dental offices in order to produce the final version, which included nine dimensions: location, patient, finance, marketing, competition, quality, staff, career, and productivity. The accuracy of the instrument was measured by intrarater and interrater reliability. In the validation phase, 247 Brazilian dentists answered a web-based questionnaire. The data were processed using Stata 13.0 and the significance level was set at 95%. The instrument had intrarater and interrater reliability (ICC-0.93 and 0.94). The overall average of respondents for the DMS-BR scale was 3.77 (SD = 0.45). Skewness and kurtosis were below absolute values 3 and 7, respectively. Internal validity measured by Cronbach's alpha was 0.925 and the correlation of each dimension with the final result of the DMS-BR ranged between 0.606 and 0.810. Correlation with the job satisfaction scale was 0.661. The SEM data ranged between 0.80 and 0.56. The questionnaire presented satisfactory indicators of dentists' self-perception about management and administration activities.

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Effects of avocado/soybean unsaponifiables (ASU) on the treatment of ligature-induced periodontitis in rats

Abstract The purpose of this study is to evaluate the effect of the avocado/soybean unsaponifiables (ASU) on the treatment of induced periodontitis in rats. Periodontitis was induced in 84 rats via ligature placement around the second upper molar, which was removed after 7 days, and scaling and root planning (SRP) was performed at this time. Subsequently, the rats were randomly allocated to four groups with 21 animals each: One SRP group in which saline solution was administered (SS), and three groups in which ASU was administered (0.6 g/kg/day), beginning either 7 days before the induction of periodontitis (SRP/ASU-7), on the day of periodontitis induction (SRP/ASU0), or on the day of treatment (SRP/ASU+7). ASU and SS were administered daily by gavage until the sacrifice of the animals (7, 15, and 30 days after SRP). The % bone in the furcation area was evaluated by histomorphometry and micro-CT. The expression of proteins (TRAP, RANKL, and alkaline phosphatase) and mRNA (IL-1β, TNF-α, IL-6, RANKL, and alkaline phosphatase) were evaluated by immunohistochemistry and qPCR. The SRP/ASU+7 group presented a higher percentage of bone fill in the furcation area and higher expression of alkaline phosphatase than in the SRP group (at 7 and 30 days, respectively). The SRP/ASU0 and SRP/ASU+7 groups presented lower expression levels of RANKL mRNA than the SRP and SRP/ASU-7 groups at 15 days. ASU administration on the day of the SRP treatment of the ligature-induced periodontitis promoted subtle beneficial effects on periodontal repair following the treatment of induced periodontitis within the experimental period of 7 days.

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Influence of root dentin treatment on the push-out bond strength of fibre-reinforced posts

Abstract This study evaluates the influence of root dentin treatment with NaOCl alone and combined with EDTA, with and without ultrasound activation, on the push-out bond strength (BS) of fiber-reinforced posts in weakened roots, cemented with RelyX or Panavia. The root canals of 42 maxillary canines were instrumented with Reciproc and 2.5% NaOCl. In the coronal 12mm of all canals, experimental weakening of the roots was produced by reducing dentin thickness with 2.44mm diameter diamond burs. The roots were assigned to 3 groups (n = 14) according to root dentin treatment: 2.5% NaOCl; 2.5% NaOCl + 17% EDTA; and 2.5% NaOCl + 17% EDTA, with solutions agitated using passive ultrasonic irrigation. After cementation of the fiber-reinforced posts the roots were divided in thirds. The first slice of each third was used for the push-out BS test, the second slice for confocal laser scanning microscopy and dentin microhardness (Knoop) analysis. Data were analysed by a two-way ANOVA and Tukey test (a = 0.05). NaOCl + EDTA provided highest BS values than NaOCl (p < 0.0001). Specimens cemented with Panavia presented significantly higher BS than those with RelyX in the three root thirds (p < 0.0001). The highest BS values occurred in the cervical third (p < 0.001). Ultrasound-activated NaOCl + EDTA promoted the greatest reduction in dentin microhardness, followed by NaOCl/EDTA and NaOCl. Ultrasonic activation of NaOCl and EDTA reduced root dentin microhardness, but did not improve the push-out BS of resin-based cements. Panavia presented higher BS than RelyX. RelyX was not influenced by the root dentin treatment protocols.

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High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Bruna C. Favoretto, Adriana A.C. Casabuono, José A. Portes-Junior, Jacqueline F. Jacysyn, Alicia S. Couto, Eliana L. Faquim-Mauro
Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs.



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Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016

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Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016

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Comparison of levetiracetam and oxcarbazepine monotherapy among Korean patients with newly diagnosed focal epilepsy: A long-term, randomized, open-label trial

Summary

This open-label, multicenter, randomized phase IV trial (NCT01498822) of noninferiority design compared the long-term effectiveness, safety, and tolerability of levetiracetam (LEV) monotherapy with those of oxcarbazepine (OXC) monotherapy in adults with newly diagnosed focal epilepsy. Korean patients (16–80 years), with ≥2 unprovoked focal seizures in the year preceding the trial, who had not taken any antiepileptic drugs (AEDs) in the last 6 months, were randomized to receive LEV or OXC (1:1). Effectiveness, safety, and tolerability were assessed over a 50-week period. Treatment failure rates (per protocol set) were 15/118 (12.7%) in the LEV-treated group and 30/128 (23.4%) in the OXC-treated group, an absolute difference of −10.7% (95% confidence interval [CI] −20.2, −1.2). Because the upper 95% CI limit was less than the pre-specified noninferiority margin of 15%, LEV was considered noninferior to OXC. Twenty-four-week and 48-week seizure freedom rates were 53.8% and 34.7% for LEV vs. 58.5% and 40.9% for OXC. Both LEV and OXC were well tolerated, with 8.7% and 8.6% of patients reporting serious treatment-emergent adverse events, respectively. By comparing LEV with OXC, another newer AED, LEV can be considered a useful option as initial monotherapy for patients with newly diagnosed focal epilepsy.

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Announcements

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Issue Information–ISSN page

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Routine Contrast Esophagram in Anastomotic Leaks After Esophagectomy: Methodological Issues on Diagnostic Value

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Health Status Disparities and the Microbiome

Bacteria of the microbiome are essential aspects of human health. The best example is in the human gut. Home to nearly three pounds of bacteria (with recent estimates at 3.8·1013 bacteria), our gut uses its microbiome to neutralize toxic byproducts of digestion, stimulate digestion, assist with ...

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Influence of an Interdisciplinary Re-employment Programme Among Unemployed Persons with Mental Health Problems on Health, Social Participation and Paid Employment

Abstract

Purpose To evaluate the influence of an interdisciplinary re-employment programme on labour force participation and perceived health among unemployed persons with common mental health problems. In addition, the influence of entering paid employment on self-rated physical health and mental health was investigated. Methods In this quasi-experimental study with 2 years follow up, 869 persons were enrolled after referral to an interdisciplinary re-employment programme (n = 380) or regular re-employment programme (n = 489). The propensity score technique was used to account for observed differences between the intervention and control group. The intervention programme was provided by an interdisciplinary team, consisting of mental health care professionals as well as employment specialists. Mental health problems were addressed through cognitive counselling and individual tailored job-search support was provided by an employment professional. Primary outcome measures were paid employment and voluntary work. Secondary outcome measures were self-rated mental and physical health, measured by the Short Form 12 Health Survey, and anxiety and depressive symptoms, measured by the Kessler Psychological Distress Scale. Changes in labour force participation and health were examined with repeated-measures logistic regression analyses by the generalized estimating equations method. Results The interdisciplinary re-employment programme did not have a positive influence on entering employment or physical or mental health among unemployed persons with mental health problems. After 2 years, 10% of the participants of the intervention programme worked fulltime, compared to 4% of the participants of the usual programmes (adjusted OR 1.65). The observed differences in labour force participation were not statistically significant. However, among persons who entered paid employment, physical health improved (+16%) and anxiety and depressive symptoms decreased (−15%), whereas health remained unchanged among persons who continued to be unemployed. Conclusions Policies to improve population health should take into account that promoting paid employment may be an effective intervention to improve health. It is recommended to invest in interdisciplinary re-employment programmes with a first place and train approach.

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