bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity
Authors: Baradaran-Heravi Alireza , Niesser Jürgen , Balgi Aruna D. , Choi Kunho , Zimmerman Carla , South Andrew P. , Anderson Hilary J. , Strynadka Natalie C. , Bally Marcel B. , Roberge Michel
Published: March 2017

Nonsense mutations underlie about 10% of rare genetic disease cases. They introduce a premature termination codon (PTC) and prevent the formation of full-length protein. Pharmaceutical gentamicin, a mixture of several related aminoglycosides, is a frequently used antibiotic in humans that can induce PTC readthrough and suppress nonsense mutations at high concentrations. However, testing of gentamicin in clinical trials has shown that safe doses of this drug produce weak and variable readthrough activity that is insufficient for use as therapy. In this study we show that the major components of pharmaceutical gentamicin lack PTC readthrough activity but the minor component gentamicin B1 (B1) is a potent readthrough inducer. Molecular dynamics simulations reveal the importance of ring I of B1 in establishing a ribosome configuration that permits pairing of a near-cognate complex at a PTC. B1 induced readthrough at all three nonsense codons in cultured cancer cells with
TP53
(tumor protein p53) mutations, in cells from patients with nonsense mutations in the
TPP1
(tripeptidyl peptidase 1),
DMD
(dystrophin),
SMARCAL1
(SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), and
COL7A1
(collagen type VII alpha 1 chain) genes, and in an in vivo tumor xenograft model. The B1 content of pharmaceutical gentamicin is highly variable and major gentamicins suppress the PTC readthrough activity of B1. Purified B1 provides a consistent and effective source of PTC readthrough activity to study the potential of nonsense suppression for treatment of rare genetic disorders.
Naturally occurring fluorescence in frogs
Authors: Taboada Carlos , Brunetti Andrés E. , Pedron Federico N. , Carnevale Neto Fausto , Estrin Darío A. , Bari Sara E. , Chemes Lucía B. , Peporine Lopes Norberto , Lagorio María G. , Faivovich Julián
Published: March 2017

Significance

In this interdisciplinary study, we report naturally occurring fluorescence in amphibians; specifically, in a common South American tree frog. We show that fluorescence is traceable to a class of compound that occurs in lymph and skin glands. Our study indicates that in our model species, in low-light conditions, fluorescence accounts for an important fraction of the total emerging light, largely enhancing brightness of the individuals and matching the sensitivity of night vision in amphibians. These findings open an exciting perspective into frog visual physiology and ecology and into the role of fluorescence in terrestrial environments, where classically it has been considered irrelevant.
Isolation and amino acid sequence of a dehydratase acting on d-erythro-3-hydroxyaspartate from Pseudomonas sp. N99, and its application in the production of optically active 3-hydroxyaspartate
Authors: Nagano Hiroyuki , Shibano Kana , Matsumoto Yu , Yokota Atsushi , Wada Masaru
Published: March 2017

An enzyme catalyzing the ammonia-lyase reaction for the conversion of d-erythro-3-hydroxyaspartate to oxaloacetate was purified from the cell-free extract of a soil-isolated bacterium Pseudomonas sp. N99. The enzyme exhibited ammonia-lyase activity toward l-threo-3-hydroxyaspartate and d-erythro-3-hydroxyaspartate, but not toward other 3-hydroxyaspartate isomers. The deduced amino acid sequence of the enzyme, which belongs to the serine/threonine dehydratase family, shows similarity to the sequence of l-threo-3-hydroxyaspartate ammonia-lyase (EC 4.3.1.16) from Pseudomonas sp. T62 (74%) and Saccharomyces cerevisiae (64%) and serine racemase from Schizosaccharomyces pombe (65%). These results suggest that the enzyme is similar to l-threo-3-hydroxyaspartate ammonia-lyase from Pseudomonas sp. T62, which does not act on d-erythro-3-hydroxyaspartate. We also then used the recombinant enzyme expressed in Escherichia coli to produce optically pure l-erythro-3-hydroxyaspartate and d-threo-3-hydroxyaspartate from the corresponding dl-racemic mixtures. The enzymatic resolution reported here is one of the simplest and the first enzymatic method that can be used for obtaining optically pure l-erythro-3-hydroxyaspartate.
Quantum size confinement in gallium selenide nanosheets: band gap tunability versus stability limitation
Authors: Andres-Penares Daniel , Cros Ana , Martínez-Pastor Juan P , Sánchez-Royo Juan F
Published: March 2017

Gallium selenide is one of the most promising candidates to extend the window of band gap values provided by existing two-dimensional semiconductors deep into the visible potentially reaching the ultraviolet. However, the tunability of its band gap by means of quantum confinement effects is still unknown, probably due to poor nanosheet stability. Here, we demonstrate that the optical band gap band of GaSe nanosheets can be tuned by ∼120 meV from bulk to 8 nm thick. The luminescent response of very thin nanosheets (<8 nm) is strongly quenched due to early oxidation. Oxidation favors the emergence of sharp material nanospikes at the surface attributable to strain relaxation. Simultaneously, incorporated oxygen progressively replaces selenium giving rise to Ga2O3, with a residual presence of Ga2Se3 that tends to desorb. These results are relevant for the development and design of visible/ultraviolet electronics and optoelectronics with tunable functionalities based on atomically thin GaSe.
A cascade of multiple proteins and lipids catalyzes membrane fusion
Authors: Wickner William , Rizo Josep
Published: March 2017

Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE assembly into trans-complexes. SNARE-domain zippering draws the bilayers into immediate apposition and provides a platform to position fusion triggers such as Sec 17/α-SNAP and/or synaptotagmin, which insert their apolar “wedge” domains into the bilayers, initiating the lipid rearrangements of fusion.
Rab GTPases: master regulators that establish the secretory and endocytic pathways
Authors: Pfeffer Suzanne R.
Published: March 2017

Several of the most important discoveries in the field of membrane traffic have come from studies of Rab GTPases by Marino Zerial and Peter Novick and their colleagues. Zerial was the first to discover that Rab GTPases represent identity markers for different membrane-bound compartments, and each Rab organizes a collection of specific effectors into function-specifying membrane microdomains to carry out receptor trafficking. Novick discovered that the order (and thus polarity) of Rab GTPases along the secretory and endocytic pathways are established by their specific, cognate guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which partner with one Rab to regulate the subsequent- and prior-acting Rabs. Such so-called Rab cascades have evolved to establish domains that contain unique Rab proteins and their cognate effectors, which drive all steps of membrane trafficking. These findings deserve much broader recognition by the biomedical research community and are highlighted here, along with open questions that require serious attention for full understanding of the molecular basis of Rab GTPase-regulated membrane trafficking in eukaryotic cells.
PathwayMapper: a collaborative visual web editor for cancer pathways and genomic data
Authors: Bahceci Istemi , Dogrusoz Ugur , La Konnor C , Babur Özgün , Gao Jianjiong , Schultz Nikolaus
Published: March 2017

Motivation

While existing network visualization tools enable the exploration of cancer genomics data, most biologists prefer simplified, curated pathway diagrams, such as those featured in many manuscripts from The Cancer Genome Atlas (TCGA). These pathway diagrams typically summarize how a pathway is altered in individual cancer types, including alteration frequencies for each gene.

Results

To address this need, we developed the web-based tool PathwayMapper, which runs in most common web browsers. It can be used for viewing pre-curated cancer pathways, or as a graphical editor for creating new pathways, with the ability to overlay genomic alteration data from cBioPortal. In addition, a collaborative mode is available that allows scientists to co-operate interactively on constructing pathways, with support for concurrent modifications and built-in conflict resolution.

Availability and Implementation

The PathwayMapper tool is accessible at http://pathwaymapper.org and the code is available on Github (https://github.com/iVis-at-Bilkent/pathway-mapper).

Supplementary information

Supplementary data are available at Bioinformatics online.
Characterization of VdASP F2 Secretory Factor from Verticillium dahliae by a Fast and Easy Gene Knockout System
Authors: Xie Chengjian , Li Qiaoling , Yang Xingyong
Published: March 2017

The vascular wilt fungus Verticillium dahliae produces persistent resting structures known as microsclerotia, which enable long-term survival of this plant pathogen in soil. The completed genome sequence of V. dahliae has facilitated large-scale investigations of individual gene functions using gene-disruption strategies based on Agrobacterium tumefaciens-mediated transformation. However, the construction of gene-deletion vectors and screening of deletion mutants have remained challenging in V. dahliae. In this study, we developed a fast and easy gene knockout system for V. dahliae using ligation-independent cloning and fluorescent screening. We identified secretory factor VdASP F2 in a T-DNA insertion library of V. dahliae and deleted the VdASP F2 gene using the developed knockout system. Phenotypic analysis suggests that VdASP F2 is not necessary for V. dahliae growth on potato dextrose agar under various stress conditions. However, on semisynthetic medium or under limited nutrient conditions at lower temperatures, the VdASP F2 deletion mutant exhibited vigorous mycelium growth, less branching, and a significant delay in melanized microsclerotial formation. Further assessment revealed that VdASP F2 was required for the expression of VDH1 and VMK1, two genes involved in microsclerotial formation. Cotton inoculated with the VdASP F2 deletion mutant wilted, demonstrating that VdASP F2 is not associated with pathogenicity under normal conditions. However, after inducing microsclerotial formation and incubation at low temperatures, cotton infected with the VdASP F2 deletion mutant did not exhibit wilt symptoms. In conclusion, our results show that VdASP F2 plays an important role in the response of V. dahliae to adverse environmental conditions and is involved in a transition to a dormant form for prolonged survival.
Further Support of Conspecificity of Oak and Mango Powdery Mildew and First Report of Erysiphe quercicola and Erysiphe alphitoides on Mango in Mainland Europe
Authors: Desprez-Loustau Marie-Laure , Massot Marie , Feau Nicolas , Fort Tania , de Vicente Antonio , Torés Juan Antonio , Ortuño Dolores Fernández
Published: March 2017

Mango leaves and inflorescences infected by powdery mildew in southern Spain were analyzed using multigene sequencing (ITS + 4 single-copy coding genes) to identify the causal agent. Erysiphe quercicola was detected in 97% out of 140 samples, collected in six different orchards in the Malaga region. Among these, a small proportion also yielded E. alphitoides (8% of all samples) and E. alphitoides was found alone in 3% of samples. A phylogenetic approach was completed by cross inoculations between oak and mango, which led to typical symptoms, supporting the conspecificity of oak and mango powdery mildews. To our knowledge, this is the first report of E. quercicola and E. alphitoides causing powdery mildew on mango trees in mainland Spain, and thus mainland Europe, based on unequivocal phylogenetic and biological evidence. Our study thus confirmed the broad host range of both E. quercicola and E. alphitoides. These results have practical implications in terms of the demonstrated ability for host range expansion in powdery mildews. They also open interesting prospects to the elucidation of molecular mechanisms underlying the ability to infect single versus multiple and unrelated host plants since these two closely related powdery mildew species belong to a small clade with both generalist and specialist powdery mildews.
The Tobacco Trichome Exudate Z-abienol and Its Relationship With Plant Resistance to Phytophthora nicotianae
Authors: Steede William T. , Ma Justin M. , Eickholt David P. , Drake-Stowe Katherine E. , Kernodle Sheri P. , Shew H. David , Danehower David A. , Lewis Ramsey S.
Published: March 2017

In previous research, we discovered a favorable quantitative trait locus (QTL) in cigar tobacco cultivar ‘Beinhart 1000’ designated as Phn15.1, which provides a high level of partial resistance to the black shank disease caused by Phytophthora nicotianae. A very close genetic association was also found between Phn15.1 and the ability to biosynthesize Z-abienol, a labdanoid diterpene exuded by the trichomes onto above-ground plant parts, and that imparts flavor and aroma characteristics to Oriental and some cigar tobacco types. Because accumulation of Z-abienol is considered to be undesirable for cultivars of other tobacco types, we herein describe a series of experiments to gain insight on whether this close association is due to genetic linkage or pleiotropy. First, in an in vitro bioassay, we observed Z-abienol and related diterpenes to inhibit hyphal growth of P. nicotianae at concentrations between 0.01 and 100 ppm. Secondly, we field-tested transgenic versions of Beinhart 1000 carrying RNAi constructs for downregulating NtCPS2 or NtABS, two genes involved in the biosynthesis of Z-abienol. Thirdly, we also field tested a recombinant inbred line population segregating for a truncation mutation in NtCPS2 leading to an interrupted Z-abienol pathway. We observed no correlation between field resistance to P. nicotianae and the ability to accumulate Z-abienol in either the transgenic materials or the mapping population. Results suggest that, although Z-abienol may affect P. nicotianae when applied at high concentrations in in vitro assays, the compound has little effect on black shank disease development under natural field conditions. Thus, it should be possible to disassociate Phn15.1-mediated black shank resistance identified in cigar tobacco cultivar Beinhart 1000 from the ability to accumulate Z-abienol, an undesirable secondary metabolite for burley and flue-cured tobacco cultivars.
Overwintering Diseased Plant Parts and Newly Infected Flowers and Fruit as Sources of Inoculum for Colletotrichum acutatum in Sour Cherry
Authors: Stensvand Arne , Børve Jorunn , Talgø Venche
Published: March 2017

Production of inoculum of Colletotrichum acutatum from both previously infected and overwintered tissue, as well as newly developed plant tissue of sour cherry (Prunus cerasus), was studied in southern Norway. Plant parts were sampled from commercial, private, or research orchards, and incubated for 2 to 14 days (time depended on tissue type) in saturated air at 20°C. In early spring, abundant sporulation was found on scales of overwintered buds and shoots. A mean of 35% infected buds in four cultivars was observed, with a maximum of 72% of the buds infected in one of the samples. Over 3 years, the seasonal production of overwintered fruit and peduncles of cv. Fanal infected the previous year was investigated. In all three years, the infected plant material was placed in the trees throughout the winter and the following growing season; in two of the years, fruit and peduncles were also placed on the ground in the autumn or the following spring. Old fruit and peduncles formed conidia throughout the season, with a peak in May and June. Spore numbers declined over the season, but the decline was more rapid for plant material on the ground than in the trees. On average over 2 years, 68.7, 24.0, or 7.3% of the inoculum came from fruit placed in the trees, placed on the ground in spring, or placed on the ground the preceding autumn, respectively. The number of fruit and peduncles attached to the trees in a planting of cv. Hardangerkirsebær was followed from February to July one year, and although there was a decline over time, fruit and/or their peduncles were still attached in substantial numbers in July, thus illustrating their potential as sources of inoculum. In observations over 2 years in a heavily infected orchard of cv. Stevnsbær, 75 and 47% of flowers and newly emerged fruit, respectively, were infected. Artificially inoculated flowers and fruit produced conidia until harvest, with a peak in mid-July. It may be concluded that previously infected and overwintered, as well as newly emerged tissue of sour cherry, may serve as sources of inoculum of C. acutatum throughout the growing season.
Anterior Trunk Mobility Does Not Predict Disability in Elderly Women With Acute Low Back Pain
Authors: Felicio Diogo Carvalho , Pereira Daniele Sirineu , Diz Juliano Bergamaschine Mata , Queiroz Barbara Zille de , Silva Juscelio Pereira da , Leopoldino Amanda Aparecida Oliveira , Pereira Leani Souza Maximo
Published: March 2017

Study Design.

Cross-sectional, ancillary study of an international multicenter epidemiological study.

Objective.

To investigate the relationship of the anterior trunk mobility with self-report and physical performance measures in elderly women with acute low back pain (LBP).

Summary of Background Data.

LBP is one of the most prevalent pain complaints in the elderly population. It is postulated that the increased range of motion of limited joints of the trunk may improve LBP and functionality of patients. Recent studies have, however, questioned the association between trunk range of motion and the functional status.

Methods.

The present study included a convenience sample of elderly women from the community aged 60 years and older who presented with a new (acute) episode of LBP. Volunteers with severe diseases and visual, hearing and mobility losses, or cognitive impairment were excluded. Trunk mobility was assessed by the fingertip-to-floor test. Functionality was assessed by the Roland-Morris Questionnaire (RMQ) and gait speed test. Statistical analysis was performed by using hierarchical linear regression model.

Results.

Data from 459 elderly women, mean age of 69.0 (6.1) years old, were used to describe this report. The additional predictive value for the inclusion of independent variable trunk mobility was only 4.4% in the RMQ score and 1.5% in the gait speed test, respectively. A reduced hierarchical linear regression model showed that the significant predictors for RMQ and gait speed test were body mass index, pain intensity, and trunk mobility.

Conclusion.

This was the first study to investigate the relationship between trunk mobility and functionality in elderly women with acute LBP. The results suggest that these clinical parameters are independent from each other.

Level of Evidence: N/A
The Use of Electronic Medical Records in Jordanian Hospitals
Authors: Tubaishat Ahmad , AL-Rawajfah Omar M.
Published: March 2017

No previous nationwide study has estimated to what extent electronic health records have been implemented in Jordanian hospitals. The purpose of this descriptive, cross-sectional study was to explore the level of adoption and use of electronic health records in Jordanian hospitals across all major healthcare service providers. The standardized American Hospital Association annual survey was used. The level of use of electronic functionalities of electronic health records was determined. The association of certain hospital characteristics with the adoption of electronic health records was examined. A proportion of 10.3% of the participating hospitals had a comprehensive use of electronic health records in all units, and 15.5% had a basic system in at least one unit. Most (74.2%, n = 72) had not implemented electronic health records. The hospitals with a higher rate of adoption were found to be larger, government, urban, and teaching hospitals that had coronary care units. The level of adoption of electronic health records in Jordan is relatively low. This fact should impel policy makers to resolve the challenges and obstacles for such adoption. National strategic plans are needed to address the goals and implementation processes of electronic health record systems in all Jordanian hospitals.
Study of Selected BRCA1, BRCA2, and PIK3CA Mutations in Benign and Malignant Lesions of Anogenital Mammary–Like Glands
Authors: Konstantinova Anastasia M. , Shelekhova Ksenya V. , Imyanitov Evgeny N. , Iyevleva Aglaya , Kacerovska Denisa , Michal Michal , Kazakov Dmitry V.
Published: March 2017

Anogenital mammary–like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selectedBRCA1,BRCA2, andPIK3CAmutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. NoBRCAmutation was detected, whereas 3 neoplasms yieldedPIK3CAmutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the wholeBRCA1andBRCA2genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.
Scrotal Melanoma: A Systematic Review of Presentation, Treatment, and Outcomes
Authors: Zikry Joseph , Chapman Lance W. , Korta Dorota Z. , Smith Janellen
Published: March 2017

BACKGROUND

Primary male genital melanomas are rare. Of these, scrotal melanoma is the least common, and is unfortunately often detected late in the disease course.

OBJECTIVE

To assess the clinical presentation, treatment modalities, and outcome of scrotal melanoma to aid clinician management.

METHODS

Systematic literature review of PubMed, yielding 23 cases, of which 20 met the inclusion criteria.

RESULTS

Although previously thought to have the best outcome of genitourinary melanomas, scrotal melanomas are associated with high mortality and late presentation. Scrotal melanoma presented as Stage I/II disease 18.75% of the time, Stage III 56.3% of the time, and Stage IV 25% of the time, whereas typical cutaneous melanoma presents as Stage I/II disease 84% of the time, Stage III 8% of the time, and Stage IV 4% of the time. Half of patients experienced recurrence of their disease. All patients who presented with metastases to distant organs died.

LIMITATIONS

Small sample size. Few cases described a Breslow's depth making it difficult to draw conclusions on tumor thickness and survival outcome.

CONCLUSION

Scrotal melanoma is rare, aggressive, and is often caught late in the disease course. The authors encourage dermatologists to educate patients and destigmatize genital lesions to increase the likelihood of earlier detection and better patient outcomes.
Preoperative Radiotherapy Is Not Associated with Increased Post-mastectomy Short-term Morbidity: Analysis of 77,902 Patients
Authors: Baltodano Pablo A. , Reinhardt Myrna Eliann , Flores José M. , Abreu Francis M. , Chattha Anmol , Kone Lyonell , Cooney Carisa M. , Manahan Michele A. , Zellars Richard C. , Rosson Gedge D.
Published: March 2017

Background:

Neoadjuvant radiotherapy (NRT) enhances breast-conserving surgery outcomes, reducing local recurrence of breast cancer and increasing median survival. However, its effect on postoperative morbidity remains under-studied. We sought to assess the impact of NRT on 30-day postoperative morbidity after mastectomy.

Methods:

We analyzed data from women undergoing mastectomy (with or without immediate reconstruction) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005–2011 datasets. ACS-NSQIP is a prospective, risk-adjusted, outcomes-based registry. Data included demographic and perioperative factors. Outcomes studied included surgical site (wound and prosthesis/flap complications), systemic (cardiac, respiratory, neurological, urinary, and venous thromboembolism events), and overall morbidity. Logistic regression was used to estimate the unadjusted odds ratio (uOR) and adjusted odds ratio (aOR) between NRT and postoperative 30-day morbidity.

Results:

The study population included 77,902 women, of which 61,039 (78.4%) underwent mastectomy only and 16,863 (21.6%) underwent mastectomy with immediate breast reconstruction. NRT was administered to 266 (0.4%) mastectomy-only and 75 (0.4%) immediate breast reconstruction patients. In the mastectomy-only group, there were no significant differences in the rates of postoperative surgical site morbidity (aOR = 1.41; 95% confidence interval (CI): 0.76–2.63; P = 0.276), systemic morbidity (aOR = 0.72; 95% CI: 0.40–1.26; P = 0.252), and overall morbidity (aOR = 0.85; 95% CI: 0.54–1.33; P = 0.477) between NRT and control groups. Similarly, no significant differences were found for these three outcomes in the immediate breast reconstruction population. Statistical power for every comparison was >80%.

Conclusions:

This study suggests that NRT is not associated with significantly higher 30-day postoperative complications among breast cancer patients undergoing mastectomy with or without immediate breast reconstruction.
CIRCINATE PARTITION-LIKE FINDINGS ON CONE MOSAIC IMAGED BY ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY IN EYES WITH INNER NUCLEAR LAYER MICROCYSTIC CHANGES
Authors: Hasegawa Tomoko , Ooto Sotaro , Makiyama Yukiko , Hata Masayuki , Miyamoto Kazuaki , Yoshimura Nagahisa
Published: March 2017

Purpose:

To report cases that showed partition-like, dark areas in the cone mosaic on adaptive optics scanning laser ophthalmoscopy (AO-SLO) images in eyes with inner nuclear layer (INL) microcystic changes.

Methods:

Eyes with INL microcystic changes were imaged by prototype AO-SLO.

Results:

An eye with Leber hereditary optic neuropathy, an eye with traumatic optic neuropathy, and an eye with retinitis pigmentosa that showed microcystic lesions in the INL were imaged by AO-SLO. The images revealed characteristic, dark, partition-like lesions in the cone mosaic of all the eyes in areas where microcystic changes in the INL were shown by spectral domain optical coherence tomography. The AO-SLO findings in eyes with optic neuropathy were quite similar in shape and size to those seen in eyes with retinitis pigmentosa.

Conclusion:

We report cases that manifest dark, partition-like areas in the cone mosaic on AO-SLO images. Microcystic lesions in the INL may affect the images of the cone mosaic.
TWO CASES OF ACUTE RETINAL NECROSIS DUE TO VARICELLA ZOSTER DESPITE PRIOR SHINGLES VACCINATION
Authors: Weinlander Eric J. , Wang Angeline L. , Jaru-ampornpan Pimkwan , Altaweel Michael M. , Nork T. Michael
Published: March 2017

Purpose:

To review two cases of acute retinal necrosis in adults due to varicella zoster virus despite prior shingles vaccination.

Methods:

Retrospective chart review.

Patients:

A 62-year-old man and a 64-year-old man with unilateral acute retinal necrosis who had shingles vaccinations 16 and 7 months before their ocular symptoms.

Results:

Polymerase chain reaction confirmation of varicella zoster virus in the anterior chambers of both patients. Both patients had good responses to oral antiviral therapy and topical and/or oral steroids.

Discussion:

These two cases demonstrate that singles vaccination is not an absolute protection against varicella zoster virus–related acute retinal necrosis. However, such vaccination may reduce the severity of the acute retinal necrosis.
Severity and Outcome of Acute-on-Chronic Liver Failure is Dependent on the Etiology of Acute Hepatic Insults
Authors: Shalimar  , Kedia Saurabh , Mahapatra Soumya J. , Nayak Baibaswata , Gunjan Deepak , Thakur Bhaskar , Acharya Subrat K.
Published: March 2017

Background:

Acute-on-chronic liver failure (ACLF) may be precipitated by various hepatic insults. The present study evaluated the outcomes of ACLF with different acute insults.

Patients and Methods:

A total of 368 ACLF patients were included. Data collected included etiologies of acute hepatic insult and underlying chronic liver disease, and organ failure. Model for end-stage liver disease (MELD), chronic liver failure consortium (CLIF)-C ACLF, and acute physiology and chronic health evaluation (APACHE) II scores were calculated. Predictors of survival were assessed by the Cox proportional hazard model.

Results:

The most frequent acute insult was active alcohol consumption [150 (40.8%) patients], followed by hepatitis B virus (HBV) [71 (19.3%) patients], hepatitis E virus (HEV) superinfection [45 (12.2%) patients], autoimmune hepatitis flare [17 (4.6%) patients], antituberculosis drugs [16 (4.3%) patients], and hepatitis A virus superinfection [2 (0.5%) patients]; 67 (18.2%) cases were cryptogenic. Alcohol-ACLF and cryptogenic-ACLF were more severe. Median CLIF-C, MELD, and APACHE II scores in alcohol-ACLF and cryptogenic-ACLF were significantly higher than those in HBV-ACLF and HEV-ACLF (CLIF-C: 47.1, 47.4 vs. 42.9, 42.0, P=0.002; MELD: 29, 29.9 vs. 28.9, 25.2, P=0.02; APACHE II: 16.5, 18.0 vs. 12, 14, P<0.001, respectively). Frequencies of kidney and brain failures were also higher in alcohol/cryptogenic-ACLF than in HBV/HEV-ACLF (kidney failure: 35.3%/34.3% vs. 23.9%/11.1%, P=0.009; brain failure: 26.0%/22.4% vs. 15.5%/4.4%, P=0.01, respectively). Mortality in the alcohol-ACLF group was the highest (64.0%), followed by that in the cryptogenic-ACLF (62.7%), HBV-ACLF (45.1%), and HEV-ACLF (17.8%) groups (P<0.001). In multivariable analysis, alcohol-ACLF had significantly higher mortality compared with HEV-ACLF (hazard ratio, 3.06; 95% confidence interval, 1.10-8.49, P=0.03).

Conclusions:

Alcohol/cryptogenic-ACLF had more severe phenotypic presentation, more incidence of organ failures, and higher mortality compared with HEV/HBV-ACLF. Alcohol-ACLF had the highest mortality, whereas HEV-ACLF had the best survival.
Medullary Carcinoma of the Penis
Authors: Cañete-Portillo Sofía , Clavero Omar , Sanchez Diego F. , Silvero Arturo , Abed Francisco , Rodriguez Ingrid M. , Ayala Gustavo , Alemany Laia , Munoz Nubia , de Sanjose Silvia , Quint Wim , Bosch Francesc X. , Cubilla Antonio L.
Published: March 2017

A third to half of penile invasive squamous cell carcinomas are human papillomavirus (HPV) related. Warty (condylomatous), warty-basaloid, and basaloid carcinomas are the most common subtypes associated with HPV. Less frequent are clear cell and lymphoepithelioma-like carcinomas. Here we report a novel penile tumor associated with HPV. Twelve cases were selected from 1010 penile carcinomas, part of an international HPV detection study conducted at the Institut Català d’Oncologia, Barcelona, Spain. Immunostaining with p16INK4a was performed on all cases, and HPV-mRNA detection was also performed. En bloc full tumor staining was the utilized criteria for positivity of p16INK4a. For HPV-DNA detection, whole-tissue section polymerase chain reaction analysis was performed by SPF10-DEIA-LiPA25 (version 1). The patients’ ages ranged from 42 to 92 years (average, 71 y). The tumor was most commonly located in the glans. A characteristic microscopic finding was the presence of a moderate to dense tumor-associated inflammatory cell infiltrate composed of neutrophils, lymphocytes, plasma cells, or eosinophils. Tumors grew in large solid sheets, nests, or had a trabecular pattern. Cells were large and poorly differentiated or anaplastic. Keratinization was minimal or absent. Nuclei were large with prominent nucleoli. Mitoses were numerous. Tumor necrosis was common. Deep invasion of the corpora cavernosa was frequent. p16INK4a and HPV-DNA were positive in all cases, whereas mRNA detection was positive in 9 cases only. The prevalent genotype was HPV16 (9 cases, 75%). Other genotypes were HPVs 58, 33, and 66. Medullary carcinomas of the penis are morphologically distinctive HPV-related high-grade neoplasms affecting older individuals. More studies are necessary to delineate the epidemiological, clinical, and molecular features of this unusual penile neoplasm.
Research Interest in Pediatric Emergency Medicine Fellows
Authors: Michelson Kenneth A. , Nigrovic Lise E. , Nagler Joshua , McAneney Constance M. , Mistry Rakesh D.
Published: March 2017

Objective

Factors predictive of research career interest among pediatric emergency medicine (PEM) fellows are not known. We sought to determine the prevalence and determinants of interest in research careers among PEM fellows.

Methods

We performed an electronically distributed national survey of current PEM fellows. We assessed demographics, barriers to successful research, and beliefs about research using 4-point ordinal scales. The primary outcome was the fellow-reported predicted percentage of time devoted to clinical research 5 years after graduation. We measured the association between barriers and beliefs and the predicted future clinical research time using the Spearman correlation coefficient.

Results

Of 458 current fellows, 231 (50.4%) submitted complete responses to the survey. The median predicted future clinical research time was 10% (interquartile range, 5%–20%). We identified no association between sex, residency type, and previous research exposure and predicted future research time. The barrier that most correlated with decreased predicted clinical research time was difficulty designing a feasible fellowship research project (Spearman coefficient [ρ], 0.20; P = 0.002). The belief that most correlated with increased predicted clinical research time was excitement about research (ρ = 0.69, P < 0.001).

Conclusions

Most fellows expect to devote a minority of their career to clinical research. Excitement about research was strongly correlated with career research interest.
Treatment of Depersonalization Disorder With Repetitive Transcranial Magnetic Stimulation
Authors: KARRIS BIANCA C. , CAPOBIANCO MARC , WEI XIN , ROSS LESLEY
Published: March 2017

High frequency repetitive transcranial magnetic stimulation (rTMS) was approved by the US Food and Drug Administration in 2008 to treat major depressive disorder in those who did not respond to at least 1 antidepressant trial. Previous studies have shown that both high frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) and low frequency rTMS to the right DLPFC have antidepressant efficacy in treatment-resistant depression. Although rTMS has been widely used in the treatment of depression, very few studies of rTMS in patients with depersonalization disorder (DPD) have been published so far. DPD involves persistent or recurrent experiences of unreality and feelings of detachment causing distress or functional impairment while insight remains intact. The prevalence of DPD is approximately 1% to 2%. Studies of the pharmacological treatment of DPD are limited, and medications have proven to be of limited benefit. We present the case of a 30-year-old man with major depressive disorder and DPD who did not respond to pharmacotherapy. After the patient was treated with low frequency rTMS to the right DLPFC followed by high frequency rTMS to the left DLPFC, there was a significant reduction in his depersonalization symptoms. Given its effectiveness in our patient, the use of both low frequency rTMS to the right DLPFC and high frequency rTMS to the left DLPFC for treatment of DPD should be further explored.
Assessing Suicide Risk: What is Commonly Missed in the Emergency Room?
Authors: ALAVI NAZANIN , RESHETUKHA TARAS , PROST ERIC , ANTONIAK KRISTEN , GROLL DIANNE
Published: March 2017

Objective:

Although risk assessment for suicide has been extensively studied, it is still an inexact process. The current study determined how busy emergency clinicians actually assessed and documented suicide risk, while also examining the differences between psychiatric and emergency medicine opinions on the importance of various suicide predictors.

Method:

Phase 1 of the study involved the administration of a survey on the relative importance of various suicide predictors for the specialties of psychiatry and emergency medicine. In phase 2 of the study, a chart review of psychiatric emergency room patients was conducted to determine the actual documentation rates of the suicide predictors.

Results:

Several predictors that were deemed to be important, including suicidal plan, intent for suicide, having means available for suicide, and practicing suicide (taking different steps leading up to suicide but not actually attempting suicide), had low documentation rates.

Conclusions:

Medical specialties have different opinions on the importance of various suicide predictors. Also, some predictors deemed important had low documentation rates. Educational interventions and simple assessment tools may help to increase documentation rates of several suicide predictors in busy clinical settings.
Performance Validity Testing in Neuropsychology: Scientific Basis and Clinical Application—A Brief Review
Authors: GREHER MICHAEL R. , WODUSHEK THOMAS R.
Published: March 2017

Performance validity testing refers to neuropsychologists’ methodology for determining whether neuropsychological test performances completed in the course of an evaluation are valid (ie, the results of true neurocognitive function) or invalid (ie, overly impacted by the patient’s effort/engagement in testing). This determination relies upon the use of either standalone tests designed for this sole purpose, or specific scores/indicators embedded within traditional neuropsychological measures that have demonstrated this utility. In response to a greater appreciation for the critical role that performance validity issues play in neuropsychological testing and the need to measure this variable to the best of our ability, the scientific base for performance validity testing has expanded greatly over the last 20 to 30 years. As such, the majority of current day neuropsychologists in the United States use a variety of measures for the purpose of performance validity testing as part of everyday forensic and clinical practice and address this issue directly in their evaluations. The following is the first article of a 2-part series that will address the evolution of performance validity testing in the field of neuropsychology, both in terms of the science as well as the clinical application of this measurement technique. The second article of this series will review performance validity tests in terms of methods for development of these measures, and maximizing of diagnostic accuracy.
Repetitive Transcranial Magnetic Stimulation and Treatment-emergent Mania and Hypomania: A Review of the Literature
Authors: RACHID FADY
Published: March 2017

Background:

This review focuses on treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS).

Methods:

English-language studies involving possible rTMS-induced mania/hypomania published between 1966 and 2015 were retrieved through a Medline search using the search terms mania, hypomania, mixed affective state, treatment-emergent, repetitive transcranial magnetic stimulation, and rTMS. Fifteen case series and controlled studies describing TEM associated with rTMS treatment have been published involving 24 individuals, most of whom were diagnosed with either bipolar I or II disorder or major depressive disorder.

Results:

rTMS has been shown to possibly induce manic or hypomanic episodes in patients with depression, who are sometimes also taking antidepressants. Both high-frequency and low-frequency rTMS with different stimulus parameters may be associated with TEM in both males and females.

Conclusions:

Given these findings, it is highly recommended that patients with bipolar disorder who are experiencing a depressive episode be prescribed a mood stabilizer and that patients diagnosed with major depressive disorder be reevaluated to consider the possibility that they might have bipolar disorder, before rTMS treatment is initiated. If TEM occurs, discontinuation of rTMS should be considered, while continuing mood-stabilizing medications. Further research is needed concerning the underlying neurobiological mechanisms and epidemiologic characteristics of TEM associated with rTMS.
Tardive Dyskinesia: A Historical Perspective
Authors: MACALUSO MATTHEW , FLYNN ALEXANDRA , PRESKORN SHELDON H.
Published: March 2017

The goal of this column is to provide historical context on tardive dyskinesia (TD) to help the reader understand how the concept was studied and evolved over time. Psychiatrists today should understand this history and consider it in combination with more recent data on the neurobiology of TD, including data from animal studies. This combination of classic data with modern science can help readers develop a more complete understanding and lead to a more judicious use of the term TD, after consideration of all of the alternative causes of abnormal movements, including spontaneous dyskinesia (SD). We advocate that clinicians use the term SD when in doubt about the cause of a movement disorder in a given patient, as TD is never distinguishable from SD in a given patient but is instead an issue of a statistical odds ratio.
Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals—Prospective Data From an Asian Cohort
Authors: Lui Grace , Ma Ronald C. W. , Chook Ping , Wong Chun-Kwok , Tam Claudia H. T. , Chan Michael H. M. , Lee Shui-Shan , Wong Rity Y. K. , Cheung Catherine S. K. , Choi Kin-Wing , Leung Ping-Chung , Wong Ka-Hing , Chan Kenny C. W. , Lee Nelson
Published: March 2017

Background:

The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort.

Setting:

A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong.

Methods:

Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses.

Results:

Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000–0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals.

Conclusions:

Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.
Temporal Trends and Rural-Urban Differences in Hospital Length of Stay for Alzheimer Disease and Related Disorders
Authors: Opoku Samuel T.Y. , Apenteng Bettye A. , Lin Ge
Published: March 2017

Objectives:

The aim of this study was to assess rural-urban differences and temporal trends in length of inpatient stay among patients diagnosed with Alzheimer disease and related dementia (ADRD).

Materials and Methods:

The study sample comprised 27,313 ADRD and 27,313 matched non-ADRD inpatient discharges from Nebraska hospitals from 2005 to 2011. Descriptive statistics and multivariable regression models were used to assess rural-urban variations and temporal trends in length of stay (LOS).

Results:

LOS was found to be similar for ADRD and non–ADRD-related hospitalizations. No rural-urban differences in LOS were observed for ADRD-related hospitalizations. However, there was a temporal decline in LOS for ADRD-related hospitalizations.

Conclusions:

LOS for ADRD-related hospitalizations was found to be influenced mostly by patient-level demographic and clinical factors. Hospital-level factors were not associated with LOS.
What is a vector?
Authors: Wilson Anthony James , Morgan Eric René , Booth Mark , Norman Rachel , Perkins Sarah Elizabeth , Hauffe Heidi Christine , Mideo Nicole , Antonovics Janis , McCallum Hamish , Fenton Andy
Published: March 2017

Many important and rapidly emerging pathogens of humans, livestock and wildlife are ‘vector-borne’. However, the term ‘vector’ has been applied to diverse agents in a broad range of epidemiological systems. In this perspective, we briefly review some common definitions, identify the strengths and weaknesses of each and consider the functional differences between vectors and other hosts from a range of ecological, evolutionary and public health perspectives. We then consider how the use of designations can afford insights into our understanding of epidemiological and evolutionary processes that are not otherwise apparent. We conclude that from a medical and veterinary perspective, a combination of the ‘haematophagous arthropod’ and ‘mobility’ definitions is most useful because it offers important insights into contact structure and control and emphasizes the opportunities for pathogen shifts among taxonomically similar species with similar feeding modes and internal environments. From a population dynamics and evolutionary perspective, we suggest that a combination of the ‘micropredator’ and ‘sequential’ definition is most appropriate because it captures the key aspects of transmission biology and fitness consequences for the pathogen and vector itself. However, we explicitly recognize that the value of a definition always depends on the research question under study.

This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.