bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of family carers of people diagnosed with borderline personality disorder
Authors: Lawn S. , McMahon J.
Published: April 2015

Accessible summary

Borderline personality disorder (BPD) is a complex and challenging mental health condition for the person and family carers who support them.

This paper reports on the results of a survey of 121 family carers of people diagnosed with BPD about their experiences of being carers, their attempts to seek help for the person diagnosed with BPD and their own carer needs. It provides the first detailed account across these domains.

Family carers of people diagnosed with BPD experience significant exclusion and discrimination when attempting to interact with generalist health and mental health services. Further education for all health professionals is indicated, particularly general practitioners who likely come into contact with BPD carers. All health professionals need to improve their skills and attitudes in working with people diagnosed with BPD, and also their skills and attitudes in working with BPD carers. Carers of people diagnosed with BPD may need specialist carer support that addresses their distinct information, education and support needs.

There is limited understanding of the experience of family carers of people diagnosed with borderline personality disorder (BPD). This study aimed to explore their experiences of being carers, their attempts to seek help for the person diagnosed with BPD and their own carer needs. An invitation to participate in an online survey was distributed to carers across multiple consumer and carer organizations and mental health services, by the Private Mental Health Consumer Carer Network (Australia) in 2011. Responses from 121 carers showed that they experience significant challenges and discrimination when attempting to engage with and seek support from health services. Comparison with consumers’ experiences (reported elsewhere) showed that these carers have a clear understanding of the discrimination faced by people with this diagnosis, largely because they also experience exclusion and discrimination. Community carer support services were perceived as inadequate. General practitioners were an important source of support; however, they and other service providers need more education and training to support attitudinal change to address discrimination, recognize carers’ needs and provide more effective support. This study provides the first detailed account of BPD carers’ experiences across a broad range of support needs and interactions with community support and health services.
Sexual Health Education in U.S. Physician Assistant Programs
Authors: Seaborne Lori A. , Prince Ronald J. , Kushner David M.
Published: April 2015

Introduction

Since the 1950s, sexual health education in medical schools has been evaluated and reported upon, but there has never been an assessment published about sexual health curricula in U.S. physician assistant (PA) programs.

Aim

The aim of this study was to gain better understanding of how PA programs cover sexual health topics.

Methods

Between January and March 2014, 181 accredited PA programs received a mailed survey inquiring about their sexual health curriculum.

Main Outcome Measures

The survey assessed general sexual health topics; lesbian, gay, bisexual, transgender (LGBT) topics; teaching methods; and the amount of time spent on sexual health education.

Results

A total of 106 programs responded (59%). Ten programs offered a required, discrete course on human sexuality. The majority incorporated training into other coursework, which is consistent with most medical schools. LGBT topics were covered less thoroughly than the general sexual health topics. Total amount of time spent on sexual health topics varied widely among programs, from a minimum of 2–4 hours to a maximum of 60 hours, with a median of 12 hours.

Conclusions

PA programs in the United States appear to compare favorably with the training offered to medical students in regard to time spent on sexual health education. Transgender issues were least well-covered of all the topics queried.
Relationship Between Female Pelvic Floor Dysfunction and Sexual Dysfunction: An Observational Study
Authors: Bortolami Arianna , Vanti Carla , Banchelli Federico , Guccione Andrew A. , Pillastrini Paolo
Published: April 2015

Introduction

The ability to express one's sexuality and engage in sexual activity requires multisystemic coordination involving many psychological functions as well as the integrity of the nervous, hormonal, vascular, immune, and neuromuscular body structures and functions.

Aim

The purpose of this study was to investigate the associations among pelvic floor function, sexual function, and demographic and clinical characteristics in a population of women initiating physical therapy evaluation and treatment for pelvic floor–related dysfunctions (urinary incontinence, pelvic organ prolapse, vulvodynia, vaginismus, and constipation).

Methods

We consented and collected completed demographic data and data related to symptoms and clinical condition on 85 consecutive patients in an outpatient physical therapy clinic. Clinical and anthropometric characteristics were analyzed descriptively. Analysis of variance and linear regression analyses were used to analyze Female Sexual Function Index (FSFI) scale ratings, whereas zero-inflated beta-binomial regression was applied to the pain subscale.

Main Outcome Measures

Main outcome measure was FSFI score, whereas the secondary outcome measure was the FSFI subscale score related to pain.

Results

Women in our sample were 38 years old on average, 33% of whom had given birth and 82% of whom had high tone pelvic floor. Being in the middle-tercile age group and exhibiting low pelvic floor tone (Beta = 6.8; 95% confidence interval [CI] = [1.4; 12.0]) were significantly associated with lower levels of sexual dysfunction. Women with low tone pelvic floor also reported lower pain (odds ratio = 4.0; 95% CI = [1.6; 9.6]), whereas younger aged and physically unsatisfied subjects were more likely not to have sexual activity in the month prior to scale measurement.

Conclusion

In female patients with pelvic floor muscle dysfunction undergoing physical therapy and rehabilitation, sexual dysfunction appears to be significantly correlated with age and high pelvic floor muscle tone.
The Relationship Between Mode of Delivery and Sexual Health Outcomes after Childbirth
Authors: Faisal-Cury Alexandre , Menezes Paulo Rossi , Quayle Julieta , Matijasevich Alicia , Diniz Simone Grilo
Published: April 2015

Introduction

Several factors are implicated in the women's sexuality after childbirth. Nevertheless, there is conflicting evidence about the influence of mode of delivery (MD)

Aim

To prospectively evaluate the relationship between MD and sexual health outcomes after childbirth

Methods

A prospective cohort study conducted between May 2005 and March 2007 included 831 pregnant women recruited from primary care clinics of the public sector in São Paulo, Brazil. The exposure variable was MD: uncomplicated vaginal delivery (spontaneous vaginal delivery without episiotomy or any kind of perineal laceration); complicated vaginal delivery (either forceps or normal, with episiotomy or any kind of perineal laceration) and cesarean delivery. Socio-demographic and obstetric data were obtained through a questionnaire applied during the antenatal and postnatal period. Crude and adjusted risk ratios, with 95% confidence intervals, were calculated using Poisson regression to examine the associations between MD and sexual health outcomes.

Main Outcome Measures

The three main sexual health outcomes were later resumption of sexual life, self-perception of decline of sexual life (DSL), and presence of sexual desire.

Results

One hundred and forty-one women (21.9%) resumed sexual life 3 or more months after delivery. Although 87.1% of women had desire, DSL occurred in 21.1% of the cohort. No associations were found between MD and sexual health outcomes.

Conclusions

Women's sexuality after childbirth were not influenced by the type of delivery. Efforts to improve the treatment of sexual problems after childbirth should focus beyond MD.
Adverse Reactions in Horses that Underwent General Anesthesia and Cervical Myelography
Authors: Mullen K.R. , Furness M.C. , Johnson A.L. , Norman T.E. , Hart K.A. , Burton A.J. , Bicahlo R.C. , Ainsworth D.M. , Thompson M.S. , Scrivani P.V.
Published: April 2015

Background

The study was prompted by a perceived high prevalence of myelographic complications varying in severity and type, and attributed to the contrast material or the procedure.

Hypotheses

1. Any adverse reaction (AAR) is associated with a change in CSF volume induced either by removal of CSF or addition of contrast material. 2. AAR occurs more frequently in horses with higher premyelography neurologic grade. 3. Nonspecific hyperthermia is attenuated by anti‐inflammatory and osmotic agents.

Animals

Horses (n = 278) that underwent myelography between 2000 and 2012 at 5 institutions: A (87), B (68), C (65), D (46), and E (12).

Methods

Multi‐institutional, retrospective, observational cross‐sectional study.

Results

AAR were observed in 95/278 (34%) horses, were associated with longer general anesthesia time (P = .04) and higher contrast‐medium volume (P = .04); euthanasia because of AAR was performed in 5/278 (2%) horses. Adverse neurologic reactions were the most common type of complication observed occurring in 15/278 (5%) and 42/235 (18%) of horses in the intra‐ and postmyelography periods. A relationship between AAR and premyelography neurologic grade was not identified (P = .31). Nonspecific hyperthermia was observed in 25/235 (11%) horses; no relationship was observed with administration of anti‐inflammatory drugs and osmotic agents (P = .30).

Conclusions and clinical importance

The category of AAR occurred in one‐third of the horses generally was mild and self‐limiting. These reactions were associated with increased contrast‐medium volume and longer anesthesia time; but, no specific procedural recommendations could be made because of small odds ratios (OR) of <2 for each 1 mL increase in contrast material and for each 1 minute of additional anesthesia time.
Seizure Disorders in 43 Cattle
Authors: D'Angelo A. , Bellino C. , Bertone I. , Cagnotti G. , Iulini B. , Miniscalco B. , Casalone C. , Gianella P. , Cagnasso A.
Published: April 2015

Background

Large animals have a relatively high seizure threshold, and in most cases seizures are acquired. No published case series have described this syndrome in cattle.

Objectives

To describe clinical findings and outcomes in cattle referred to the Veterinary Teaching Hospital of the University of Turin (Italy) because of seizures.

Animals

Client‐owned cattle with documented evidence of seizures.

Methods

Medical records of cattle with episodes of seizures reported between January 2002 and February 2014 were reviewed. Evidence of seizures was identified based on the evaluation of seizure episodes by the referring veterinarian or 1 of the authors. Animals were recruited if physical and neurologic examinations were performed and if diagnostic laboratory test results were available.

Results

Forty‐three of 49 cases fulfilled the inclusion criteria. The mean age was 8 months. Thirty‐one animals were male and 12 were female. Piedmontese breed accounted for 39/43 (91%) animals. Seizures were etiologically classified as reactive in 30 patients (70%) and secondary or structural in 13 (30%). Thirty‐six animals survived, 2 died naturally, and 5 were euthanized for reasons of animal welfare. The definitive cause of reactive seizures was diagnosed as hypomagnesemia (n = 2), hypocalcemia (n = 12), and hypomagnesemia‐hypocalcemia (n = 16). The cause of structural seizures was diagnosed as cerebrocortical necrosis (n = 8), inflammatory diseases (n = 4), and lead (Pb) intoxication (n = 1).

Conclusion and Clinical Importance

The study results indicate that seizures largely are reported in beef cattle and that the cause can be identified and successfully treated in most cases.
Bud protection: a key trait for species sorting in a forest–savanna mosaic
Authors: Charles‐Dominique Tristan , Beckett Heath , Midgley Guy F. , Bond William J.
Published: April 2015

Contrasting fire regimes maintain patch mosaics of savanna, thicket and forest biomes in many African subtropical landscapes. Species dominating each biome are thus expected to display distinct fire‐related traits, commonly thought to be bark related. Recent Australian savanna research suggests that bud position, not bark protection alone, determines fire resilience via resprouting.

We tested first how bud position influences resprouting ability in 17 tree species. We then compared the effect of both bark‐related protection and bud position on the distribution of 63 tree species in 253 transects in all three biomes.

Tree species with buds positioned deep under bark had a higher proportion of post‐fire aboveground shoot resprouting. Species with low bud protection occurred in fire‐prone biomes only if they could root‐sucker. The effect of bud protection was supported by a good relationship between species bud protection and distribution across a gradient of fire frequency.

Bud protection and high bark production are required to survive frequent fires in savanna. Forests are fire refugia hosting species with little or no bud protection and thin bark. Root‐suckering species occur in the three biomes, suggesting that fire is not the only factor filtering this functional type.
Endosymbiont evolution: predictions from theory and surprises from genomes
Authors: Wernegreen Jennifer J.
Published: April 2015

Genome data have created new opportunities to untangle evolutionary processes shaping microbial variation. Among bacteria, long‐term mutualists of insects represent the smallest and (typically) most AT‐rich genomes. Evolutionary theory provides a context to predict how an endosymbiotic lifestyle may alter fundamental evolutionary processes—mutation, selection, genetic drift, and recombination—and thus contribute to extreme genomic outcomes. These predictions can then be explored by comparing evolutionary rates, genome size and stability, and base compositional biases across endosymbiotic and free‐living bacteria. Recent surprises from such comparisons include genome reduction among uncultured, free‐living species. Some studies suggest that selection generally drives this streamlining, while drift drives genome reduction in endosymbionts; however, this remains an hypothesis requiring additional data. Unexpected evidence of selection acting on endosymbiont GC content hints that even weak selection may be effective in some long‐term mutualists. Moving forward, intraspecific analysis offers a promising approach to distinguish underlying mechanisms, by testing the null hypothesis of neutrality and by quantifying mutational spectra. Such analyses may clarify whether endosymbionts and free‐living bacteria occupy distinct evolutionary trajectories or, alternatively, represent varied outcomes of similar underlying forces.
Attachment‐related differences in secrecy and rumination in romantic relationships
Authors: MERRILL ANNE F. , AFIFI TAMARA D.
Published: April 2015

The study examined attachment‐related predispositions and patterns of cognition and emotion that contribute to different secret‐keeping experiences. Participants (n = 380) reported on their secret keeping, rumination, attachment anxiety, and attachment avoidance via online questionnaires. Results showed that both anxiety and avoidance were positively associated with keeping a secret from a romantic partner, while only avoidance was associated with a greater total number of secrets kept. The association between avoidance and rumination was partially mediated by perceptions of a partner's ownership rights to the secret and guilt for keeping the secret, such that those who were highly avoidant were less likely to perceive a partner's ownership rights. Finally, highly anxious participants reported higher levels of rumination, which were mediated by feelings of guilt for keeping a secret. The study extends research on the link between secrecy and rumination by offering a theoretical account based on attachment for why some people are more likely to ruminate about their secrecy than others.
Risk Factors, Warning Signs, and Drivers of Suicide: What Are They, How Do They Differ, and Why Does It Matter?
Authors: Tucker Raymond P. , Crowley Kevin J. , Davidson Collin L. , Gutierrez Peter M.
Published: April 2015

Research investigating suicide attempts and deaths by suicide has yielded many specific risk factors and warning signs for future suicidal behaviors. Yet, even though these variables are each valuable for suicide prevention efforts, they may be limited in their applicability to clinical practice. The differences among risk factors, warning signs, and “drivers,” which are person‐specific variables that lead individuals to desire death by suicide, are highlighted. The scarce evidence on drivers is described and specific recommendations for conducting future drivers‐focused research and targeting them in clinical practice are suggested.
Comparing Two Measures of Social Movement Identity: The Environmental Movement as an Example
Authors: McCright Aaron M. , Dunlap Riley E.
Published: April 2015

Objective

We compare the relative performance of two measures of identification with the environmental movement: a self‐identified environmentalist indicator and an environmental movement identity indicator.

Methods

We utilize data from the March/April 2000–2010 Gallup Polls to examine how these two measures of identification with the environmental movement are related to membership in environmental organizations, attitudes toward the environmental movement, and private and public environmental behaviors.

Results

While both indicators similarly predict self‐reported private environmental behaviors, the environmental movement identity indicator is more strongly associated with membership in environmental organizations and attitudes toward the environmental movement, and the self‐identified environmentalist indicator is more strongly associated with self‐reported public environmental behaviors.

Conclusions

Given the performance of the environmental movement identity measure, we lay out an agenda for future research using a slightly revised version of the indicator to investigate identification with a range of social movements via surveys of nationally representative samples of the general public.
Genetic polymorphisms and expression of HLA‐G and its receptors, KIR2DL4 and LILRB1, in non‐small cell lung cancer
Authors: Wiśniewski A. , Kowal A. , Wyrodek E. , Nowak I. , Majorczyk E. , Wagner M. , Pawlak‐Adamska E. , Jankowska R. , Ślesak B. , Frydecka I. , Kuśnierczyk P.
Published: April 2015

Human leukocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule absent from most normal tissues but detected in many malignant tumors. It is recognized by cells of the immune system using LILRB1, KIR2DL4 and LILRB2 receptors. We attempted to find out whether some polymorphisms of HLA‐G, LILRB1 and KIR2DL4 genes are associated with susceptibility to nonsmall cell lung cancer (NSCLC). Four polymorphisms in HLA‐G, i.e. −964A>G (rs1632947), −725C>G>T (rs1233334), −716T>G (rs2249863) in the promoter, and a 14 base pair insertion/deletion (14 bp indel) in the 3′‐untranslated region (3′UTR), and five in LILRB1 – 5651G>A (rs41308748) in intron 14, 5717C>T L622L (rs1061684), 5724G>A E625K (rs16985478), 5774 C>A P641P (rs41548213) in exon 15, and 5806C>T (rs8101240) in 3′UTR – as well as 9620 9A/10A (rs11410751) polymorphism in exon 7 of KIR2DL4 were typed using different laboratory techniques. Only one single nucleotide polymorphism (SNP) in HLA‐G (‐964A>G) and one in LILRB1 (5724G>A) were found to influence the risk of NSCLC. In addition, 5724G>A was associated with protection from tumor cell infiltration of regional lymph nodes. Most importantly, we detected HLA‐G and LILRB1 expression in tumor specimens, but no correlation with genetic polymorphisms was observed. HLA‐G and LILRB1 protein expression levels in tumor tissue were significantly correlated with tumor stage.
Role of granulocyte transfusions in invasive fusariosis: systematic review and single‐center experience
Authors: Kadri Sameer S. , Remy Kenneth E. , Strich Jeffrey R. , Gea‐Banacloche Juan , Leitman Susan F.
Published: April 2015

BACKGROUND

Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia.

STUDY DESIGN AND METHODS

We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single‐center case series detailing our experience (1996‐2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone‐ and granulocyte–colony‐stimulating factor–stimulated donors.

RESULTS

Twenty‐three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor‐stimulated GTs generated mean “same‐day” neutrophil increments of 3.35 × 109 ± 1.24 × 109/L and mean overall posttransfusion neutrophil increments of 2.46 × 109 ± 0.85 × 109/L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT‐related HLA alloimmunization.

CONCLUSION

In patients with IF, donor‐stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.
The efficacy and safety of sirolimus‐based graft‐versus‐host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta‐analysis of randomized controlled trials
Authors: Wang Li , Gu Zhenyang , Zhai Ruiren , Li Dandan , Zhao Shasha , Luo Lan , Zhao Xiaoli , Wei Huaping , Pang Zhaoxia , Wang Lili , Liu Daihong , Wang Quanshun , Gao Chunji
Published: April 2015

BACKGROUND

The efficacy and safety of sirolimus (SIR)‐based graft‐versus‐host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remain to be clarified; this meta‐analysis was conducted to evaluate these factors.

STUDY DESIGN AND METHODS

Data from original research were obtained from PubMed, Embase, and Cochrane central register of controlled trials databases. Randomized controlled trials (RCTs) evaluating the efficacy of SIR‐based prophylaxis in allo‐HSCT were included. The risk ratio (RR), with a 95% confidence interval (CI), was used to pool data. The random effects model was used, irrespective of the presence or absence of heterogeneity.

RESULTS

Five RCTs were included in the meta‐analysis. SIR was observed to significantly decrease the incidence of Grade II to IV acute GVHD (aGVHD; RR, 0.65; 95% CI, 0.47‐0.89). However, the incidence of Grade III to IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59‐1.40; RR, 1.04; 95% CI, 0.88‐1.23, respectively). An analysis of the toxic effects of SIR revealed that SIR effected a significant increase in the incidence of sinusoidal obstructive syndrome (RR, 2.24; 95% CI, 1.26‐4.01), while that of thrombotic microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87‐7.06). Moreover, SIR did not improve event‐free survival and overall survival (RR, 0.97; 95% CI, 0.85‐1.10; and RR, 0.92; 95% CI, 0.82‐1.02, respectively).

CONCLUSION

This meta‐analysis indicated that the SIR‐based regimen is an effective and safe alternative prophylaxis strategy for GVHD.
A simple genotyping procedure without DNA extraction to identify rare blood donors
Authors: Silvy M. , Brès J.‐C. , Grimaldi A. , Movia C. , Muriel V. , Roubinet F. , Chiaroni J. , Bailly P.
Published: April 2015

Background

Transfusion‐induced alloimmunization has severe clinical consequences including haemolytic transfusion reactions, impaired transfused RBCs longevity and greater difficulty in finding compatible blood. Molecular analysis of genomic DNA now permits prediction of blood group phenotypes based on identification of single nucleotide polymorphisms. Implementation of molecular technologies in donor centres would be helpful in finding RBC units for special patient populations, but DNA extraction remains an obstacle to donor genotyping.

Materials and Methods

We propose a simple method compatible with high throughput that allows blood group genotyping using a multiplex commercial kit without the need for DNA extraction. The principle relies on pre‐PCR treatment of whole blood using heating/cooling procedure in association with a recombinant hotstart polymerase.

Results

In a prospective analysis, we yielded 5628 alleles identification and designated 63 donors with rare blood, that is either negative for a high‐frequency antigen or with a rare combination of common antigens.

Conclusion

The procedure was optimized for simplicity of use in genotyping platform and would allow not only to supply antigen‐matched products to recipients but also to find rare phenotypes. This methodology could also be useful for establishing a donor repository for human platelet antigens (HPA)‐matched platelets since the same issues are involved for patients with neonatal alloimmune thrombocytopenia or post‐transfusion purpura.
‘Fine‐tuning’ blood flow to the exercising muscle with advancing age: an update
Authors: Wray D. Walter , Richardson Russell S.
Published: April 2015

New Findings

What is the topic of this review?

This review focuses on age‐related changes in the regulatory pathways that exist at the unique interface between the vascular smooth muscle and the endothelium of the skeletal muscle vasculature, and how these changes contribute to impairments in exercising skeletal muscle blood flow in the elderly.

What advances does it highlight?

Several recent in vivo human studies from our group and others are highlighted that have examined age‐related changes in nitric oxide, endothelin‐1, alpha adrenergic, and renin‐angiotensin‐aldosterone (RAAS) signaling.

During dynamic exercise, oxygen demand from the exercising muscle is dramatically elevated, requiring a marked increase in skeletal muscle blood flow that is accomplished through a combination of systemic sympathoexcitation and local metabolic vasodilatation. With advancing age, the balance between these factors appears to be disrupted in favour of vasoconstriction, leading to an impairment in exercising skeletal muscle blood flow in the elderly. This ‘hot topic’ review aims to provide an update to our current knowledge of age‐related changes in the neural and local mechanisms that contribute to this ‘fine‐tuning’ of blood flow during exercise. The focus is on results from recent human studies that have adopted a reductionist approach to explore how age‐related changes in both vasodilators (nitric oxide) and vasoconstrictors (endothelin‐1, α‐adrenergic agonists and angiotensin II) interact and how these changes impact blood flow to the exercising skeletal muscle with advancing age.
Reduced-Order Observer Design for Discrete-Time Descriptor Systems With Unknown Inputs: An Linear Matrix Inequality Approach
Authors: Guo Shenghui , Zhu Fanglai
Published: April 2015

Reduced-order observer design methods for both linear and nonlinear discrete-time descriptor systems based on the linear matrix inequality (LMI) approach are investigated. We conclude that the conditions under which a full-order observer exists can also guarantee the existence of a reduced-order observer. By choosing a special reduced-order observer gain matrix, a reduced-order unknown input observer is proposed for linear system with unknown inputs, and then an unknown input reconstruction is provided for some special cases. We also extend above results to the cases of nonlinear systems. Finally, three numerical comparative simulation examples are given to illustrate the effectiveness and merits of proposed methods.
Sintered Cr/Pt and Ni/Au ohmic contacts to B12P2
Authors: Frye Clint D. , Kucheyev Sergei O. , Edgar James H. , Voss Lars F. , Conway Adam M. , Shao Qinghui , Nikolić Rebecca J.
Published: April 2015

Icosahedral boron phosphide (B12P2) is a wide-bandgap semiconductor possessing interesting properties such as high hardness, chemical inertness, and the reported ability to self-heal from irradiation by high energy electrons. Here, the authors developed Cr/Pt and Ni/Au ohmic contacts to epitaxially grown B12P2 for materials characterization and electronic device development. Cr/Pt contacts became ohmic after annealing at 700 °C for 30 s with a specific contact resistance of 2 × 10−4 Ω cm2, as measured by the linear transfer length method. Ni/Au contacts were ohmic prior to any annealing, and their minimum specific contact resistance was ∼l–4 × 10−4 Ω cm2 after annealing over the temperature range of 500–800 °C. Rutherford backscattering spectrometry revealed a strong reaction and intermixing between Cr/Pt and B12P2 at 700 °C and a reaction layer between Ni and B12P2 thinner than ∼25 nm at 500 °C.
Silicon etching in a pulsed HBr/O2 plasma. II. Pattern transfer
Authors: Haass Moritz , Darnon Maxime , Cunge Gilles , Joubert Olivier
Published: April 2015

The strong impact of synchronized plasma pulsing on an HBr/O2 silicon pattern etch process is studied with respect to the continuous process. This article focuses on blanket etch rates and a detailed analysis of the etched profiles, where several significant features of plasma pulsing are identified. First, the time compensated (TC) silicon etch rate is increased while the SiO2 TC etch rate is decreased at a low duty cycle, whereby the selectivity between silicon and SiO2 etching is strongly increased. Furthermore, the thickness of the sidewall passivation layer is reduced, thereby guiding the etched profile. Finally, the overall homogeneity is increased compared to the continuous wave etching process.
Brazil roils waters with moves to protect aquatic life
Authors: Escobar Herton
Published: April 2015

Fishing moratorium draws fire from industry and scientists.
Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit
Authors: Das Indrajit , Krzyzosiak Agnieszka , Schneider Kim , Wrabetz Lawrence , D’Antonio Maurizio , Barry Nicholas , Sigurdardottir Anna , Bertolotti Anne
Published: April 2015

Giving protein folding a helping hand

The reversible phosphorylation of proteins controls virtually all aspects of cell and organismal function. Targeting phosphorylation offers a broad range of therapeutic opportunities, and thus kinases have become important therapeutic targets. As targets, phosphatases should be as attractive, but in fact they are more challenging to manipulate. Das
et al.
have found a safe and specific inhibitor, called Sephin1, that targets a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 binds and inhibits PPP1R15A, but not the related regulatory phosphatase PPP1R15B. In mice, Sephin1 prolonged a stress-induced phospho-signaling pathway to prevent the pathological defects of the unrelated protein-misfolding diseases Charcot-Marie-Tooth 1B and amyotrophic lateral sclerosis.

Science
, this issue p.
239
Assembling a complex quantum ensemble
Authors: Spielman I. B.
Published: April 2015

A cold-atom technique is used to identify hidden constraints in thermodynamic ensembles

[Also see Report by

Langen
et al.

]
Molecular Chaperone Hsp90 Is a Therapeutic Target for Noroviruses
Authors: Vashist Surender , Urena Luis , Gonzalez-Hernandez Mariam B. , Choi Jayoung , de Rougemont Alexis , Rocha-Pereira Joana , Neyts Johan , Hwang Seungmin , Wobus Christiane E. , Goodfellow Ian
Published: April 2015

Human noroviruses (HuNoV) are a significant cause of acute gastroenteritis in the developed world, and yet our understanding of the molecular pathways involved in norovirus replication and pathogenesis has been limited by the inability to efficiently culture these viruses in the laboratory. Using the murine norovirus (MNV) model, we have recently identified a network of host factors that interact with the 5′ and 3′ extremities of the norovirus RNA genome. In addition to a number of well-known cellular RNA binding proteins, the molecular chaperone Hsp90 was identified as a component of the ribonucleoprotein complex. Here, we show that the inhibition of Hsp90 activity negatively impacts norovirus replication in cell culture. Small-molecule-mediated inhibition of Hsp90 activity using 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) revealed that Hsp90 plays a pleiotropic role in the norovirus life cycle but that the stability of the viral capsid protein is integrally linked to Hsp90 activity. Furthermore, we demonstrate that both the MNV-1 and the HuNoV capsid proteins require Hsp90 activity for their stability and that targeting Hsp90
in vivo
can significantly reduce virus replication. In summary, we demonstrate that targeting cellular proteostasis can inhibit norovirus replication, identifying a potential novel therapeutic target for the treatment of norovirus infections.

IMPORTANCE
HuNoV are a major cause of acute gastroenteritis around the world. RNA viruses, including noroviruses, rely heavily on host cell proteins and pathways for all aspects of their life cycle. Here, we identify one such protein, the molecular chaperone Hsp90, as an important factor required during the norovirus life cycle. We demonstrate that both murine and human noroviruses require the activity of Hsp90 for the stability of their capsid proteins. Furthermore, we demonstrate that targeting Hsp90 activity
in vivo
using small molecule inhibitors also reduces infectious virus production. Given the considerable interest in the development of Hsp90 inhibitors for use in cancer therapeutics, we identify here a new target that could be explored for the development of antiviral strategies to control norovirus outbreaks and treat chronic norovirus infection in immunosuppressed patients.
Genomic, Phylogenetic, and Recombinational Characterization of Herpes Simplex Virus 2 Strains
Authors: Kolb Aaron W. , Larsen Inna V. , Cuellar Jacqueline A. , Brandt Curtis R.
Published: April 2015

Herpes simplex virus 2 (HSV-2) is a major global pathogen, infecting 16% of people 15 to 49 years old worldwide and causing recurrent genital ulcers. Little is known about viral factors contributing to virulence, and there are currently only two genomic sequences available. In this study, we determined nearly complete genomic sequences of six additional HSV-2 isolates, using Illumina MiSeq. We report that HSV-2 has a genomic overall mean distance of 0.2355%, which is less than that of HSV-1. There were approximately 100 amino-acid-encoding and indels per genome. Microsatellite mapping found a bias toward intergenic regions in the nonconserved microsatellites and a genic bias in all detected tandem repeats. Extensive recombination between the HSV-2 strains was also strongly implied. This was the first study to analyze multiple HSV-2 sequences, and the data will be valuable in future evolutionary, virulence, and structure-function studies.

IMPORTANCE
HSV-2 is a significant worldwide pathogen, causing recurrent genital ulcers. Here we present six nearly complete HSV-2 genomic sequences, and, with the addition of two previously sequenced strains, for the first time genomic, phylogenetic, and recombination analysis was performed on multiple HSV-2 genomes. Our results show that microsatellite mapping found a bias toward intergenic regions in the nonconserved microsatellites and a genic bias in all detected tandem repeats and confirm that chimpanzee herpesvirus 1 (ChHV-1) is a separate species and that each of the HSV-2 strains is a genomic mosaic.
Murine Gammaherpesvirus 68 Pathogenesis Is Independent of Caspase-1 and Caspase-11 in Mice and Impairs Interleukin-1β Production upon Extrinsic Stimulation in Culture
Authors: Cieniewicz Brandon , Dong Qiwen , Li Gang , Forrest James C. , Mounce Bryan C. , Tarakanova Vera L. , van der Velden Adrianus , Krug Laurie T.
Published: April 2015

Gammaherpesviruses establish lifelong infections that are associated with the development of cancer. These viruses subvert many aspects of the innate and adaptive immune response of the host. The inflammasome, a macromolecular protein complex that controls inflammatory responses to intracellular danger signals generated by pathogens, is both activated and subverted during human gammaherpesvirus infection in culture. The impact of the inflammasome response on gammaherpesvirus replication and latencyin vivois not known. Caspase-1 is the inflammasome effector protease that cleaves the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. We infectedcaspase-1-deficient mice with murine gammaherpesvirus 68 (MHV68) and observed no impact on acute replication in the lung or latency and reactivation from latency in the spleen. This led us to examine the effect of viral infection on inflammasome responses in bone marrow-derived macrophages. We determined that infection of macrophages with MHV68 led to a robust interferon response but failed to activate caspase-1 or induce the secretion of IL-1β. In addition, MHV68 infection led to a reduction in IL-1β production after extrinsic lipopolysaccharide stimulation or upon coinfection withSalmonella entericaserovar Typhimurium. Interestingly, this impairment occurred at the proIL-1β transcript level and was independent of the RTA, the viral lyticreplication andtranscriptionactivator. Taken together, MHV68 impairs the inflammasome response by inhibiting IL-1β production during the initial stages of infection.

IMPORTANCEGammaherpesviruses persist for the lifetime of the host. To accomplish this, they must evade recognition and clearance by the immune system. The inflammasome consists of proteins that detect foreign molecules in the cell and respond by secreting proinflammatory signaling proteins that recruit immune cells to clear the infection. Unexpectedly, we found that murine gammaherpesvirus pathogenesis was not enhanced in mice lackingcaspase-1, a critical inflammasome component. This led us to investigate whether the virus actively impairs the inflammasome response. We found that the inflammasome was not activated upon macrophage cell infection with murine gammaherpesvirus 68. Infection also prevented the host cell inflammasome response to other pathogen-associated molecular patterns, indicated by reduced production of the proinflammatory cytokine IL-1β upon bacterial coinfection. Taken together, murine gammaherpesvirus impairment of the inflammatory cytokine IL-1β in macrophages identifies one mechanism by which the virus may inhibit caspase-1-dependent immune responses in the infected animal.
SRSF1 RNA Recognition Motifs Are Strong Inhibitors of HIV-1 Replication
Authors: Paz Sean , Lu Michael L. , Takata Hiroshi , Trautmann Lydie , Caputi Massimo
Published: April 2015

Replication of the integrated HIV-1 genome is tightly regulated by a series of cellular factors. In previous work we showed that transactivation of the HIV-1 promoter is regulated by the cellular splicing factor SRSF1. Here we report that SRSF1 can downregulate the replication of B, C, and D subtype viruses by >200-fold in a cell culture system. We show that viral transcription and splicing are inhibited by SRSF1 expression. Furthermore, SRSF1 deletion mutants containing the protein RNA-binding domains but not the arginine serine-rich activator domain can downregulate viral replication by >2,000-fold with minimal impact on cell viability and apoptosis. These data suggest a therapeutic potential for SRSF1 and its RNA-binding domains.

IMPORTANCE
Most drugs utilized to treat the HIV-1 infection are based on compounds that directly target proteins encoded by the virus. However, given the high viral mutation rate, the appearance of novel drug-resistant viral strains is common. Thus, there is a need for novel therapeutics with diverse mechanisms of action. In this study, we show that the cellular protein SRSF1 is a strong inhibitor of viral replication. Furthermore, expression of the SRSF1 RNA-binding domains alone can inhibit viral replication by >2,000-fold in multiple viral strains without impacting cell viability. Given the strong antiviral properties of this protein, the RNA-binding domains, and the minimal effects observed on cell metabolism, further studies are warranted to assess the therapeutic potential of peptides derived from these sequences.
Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5′ Untranslated Region
Authors: Thibault Patricia A. , Huys Adam , Amador-Cañizares Yalena , Gailius Julie E. , Pinel Dayna E. , Wilson Joyce A.
Published: April 2015

miR-122 is a liver-specific microRNA (miRNA) that binds to two sites (S1 and S2) on the 5′ untranslated region (UTR) of the hepatitis C virus (HCV) genome and promotes the viral life cycle. It positively affects viral RNA stability, translation, and replication, but the mechanism is not well understood. To unravel the roles of miR-122 binding at each site alone or in combination, we employed miR-122 binding site mutant viral RNAs, Hep3B cells (which lack detectable miR-122), and complementation with wild-type miR-122, an miR-122 with the matching mutation, or both. We found that miR-122 binding at either site alone increased replication equally, while binding at both sites had a cooperative effect. Xrn1 depletion rescued miR-122-unbound full-length RNA replication to detectable levels but not to miR-122-bound levels, confirming that miR-122 protects HCV RNA from Xrn1, a cytoplasmic 5′-to-3′ exoribonuclease, but also has additional functions. In cells depleted of Xrn1, replication levels of S1-bound HCV RNA were slightly higher than S2-bound RNA levels, suggesting that both sites contribute, but their contributions may be unequal when the need for protection from Xrn1 is reduced. miR-122 binding at S1 or S2 also increased translation equally, but the effect was abolished by Xrn1 knockdown, suggesting that the influence of miR-122 on HCV translation reflects protection from Xrn1 degradation. Our results show that occupation of each miR-122 binding site contributes equally and cooperatively to HCV replication but suggest somewhat unequal contributions of each site to Xrn1 protection and additional functions of miR-122.

IMPORTANCE
The functions of miR-122 in the promotion of the HCV life cycle are not fully understood. Here, we show that binding of miR-122 to each of the two binding sites in the HCV 5′ UTR contributes equally to HCV replication and that binding to both sites can function cooperatively. This suggests that active Ago2–miR-122 complexes assemble at each site and can cooperatively promote the association and/or function of adjacent complexes, similar to what has been proposed for translation suppression by adjacent miRNA binding sites. We also confirm a role for miR-122 in protection from Xrn1 and provide evidence that miR-122 has additional functions in the HCV life cycle unrelated to Xrn1. Finally, we show that each binding site may contribute unequally to Xrn1 protection and other miR-122 functions.
Fifteen-minute consultation: The child with short stature
Authors: Amin Nadia , Mushtaq Talat , Alvi Sabah
Published: April 2015

Short stature can be a cause of distress for children and families. It is not usually pathological, but it is important to identify treatable conditions. This article presents a systematic approach to the evaluation of a child with short stature, covering differential diagnoses, first line investigations and indications for treatment with growth hormone.
Multiple endocrine neoplasia syndromes 1 and 2: manifestations and management in childhood and adolescence
Authors: Giri D , McKay V , Weber A , Blair JC
Published: April 2015

The identification of the genetic causes of the multiple endocrine neoplasia (MEN) syndromes 1 and 2, and associated genotype–phenotype relationships, has revolutionised the clinical care of affected patients. A genetic diagnosis can be made during infancy and careful clinical surveillance, coupled with early intervention, has the potential to improve both morbidity and mortality. These developments have seen the management of patients with MEN move into the arena of paediatric medicine. In this review article, we consider the genetic causes of MEN together with the clinical manifestations and management of these syndromes.
Acute penile pain and swelling in a 4-year-old child with Henoch-Schönlein purpura
Authors: Tewary Kishor Kumar , Khodaghalian Bernadette , Narchi Hassib
Published: April 2015

Henoch-Schönlein purpura (HSP) is the most common vasculitis found in children. It usually affects the small vessels of the skin, joints, gastrointestinal tract and, more rarely, kidneys, brain, lungs and genitalia. Apart from classical presentation with purpuric rashes around buttocks and lower extremities, features such as arthralgia, abdominal pain, haematuria and proteinuria as well as scrotal swelling have been described in the literature. Penile involvement is rare and is not commonly described. We describe a child with HSP who developed penile involvement. We review the literature of all the cases reported in detail, in order to highlight useful clinical presentation, management and prognosis of this rare manifestation.
Family as the primary caregiver: palliative care in the Golan Heights
Authors: Richman Elon , Ringel Amit , Kreniske Jonah Susser , Safadi Wajdi
Published: April 2015

Palliative care is recognised by the WHO as an essential component of care for the seriously ill. Geographically isolated and historically underserved communities, particularly from ethnic minority groups, face obstacles in obtaining adequate palliative care. This case involves the care of a 26-year-old Druze man suffering from a terminal cancer in his Golan Heights village. Local physicians were able to train the patient's father in a palliative care capacity. In the effort of capacity building, the physician and palliative care team also aided the aggrieved family in the process of coping. Robust support networks, both at state and community levels, facilitated the care provided. In showcasing the role of the national and local safety net in activating and building community resources to address a dearth of palliative care services in disadvantaged regions, this case models a potentially effective community-based approach to palliative care for patients from underserved populations.
Femoral hernia, a rare complication following deep inguinal lymph node dissection
Authors: Muus Steffensen Signe , Ahm Sørensen Jens
Published: April 2015

A 72-year-old woman underwent complete deep inguinal lymph node dissection on her right side subsequent to metastasis from malignant melanoma. On the second postoperative day, the patient reported of nausea and vomiting. She presented with a mass in the resected area that gradually increased in size to approximately 15×20 cm. The wound was opened a few hours after onset of symptoms and a large femoral hernia with 40 cm of small intestine was immediately revealed protruding in the groin. Prophylactic suturing of the inguinal ligament and Coopers ligament can reduce the risk of postoperative femoral hernia. Further, the authors argue that drainage for seroma and haematoma should be performed with utmost care, considering other possible causes and, if necessary, guided by ultrasonography.