bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral Factors Associated With the High Mortality Related to Human Infections With Clade 2.1 Influenza A/H5N1 Virus in Indonesia
Authors: Pawestri Hana A , Eggink Dirk , Isfandari Siti , Thanh Tran Tan , Rogier van Doorn H , Setiawaty Vivi , de Jong Menno D
Published: April 2019

Background

Since their emergence in Indonesia in 2005, 200 human infections with clade 2.1 highly pathogenic avian influenza A/H5N1 virus have been reported, associated with exceptionally high mortality (84%) compared to regions affected by other genetic clades of this virus. To provide potential clues towards understanding this high mortality, detailed clinical virological analyses were performed in specimens from 180 H5N1 patients, representing 90% of all Indonesian patients and 20% of reported H5N1-infected patients globally.

Methods

H5N1 RNA was quantified in available upper- and lower-respiratory tract specimens as well as fecal and blood samples from 180 patients with confirmed infection between 2005 and 2017. Mutations in the neuraminidase and M2 genes that confer resistance to oseltamivir and adamantanes were assessed. Fatal and nonfatal cases were compared.

Results

High viral RNA loads in nasal and pharyngeal specimens were associated with fatal outcome. Mortality increased over time during the study period, which correlated with increasing viral RNA loads on admission. Furthermore, the prevalence of amantadine resistance–conferring M2 mutations increased over time, and viral loads were higher in patients infected with viruses that harbored these mutations. Compared to observations from other regions, viral RNA was detected more frequently in feces (80%) and particularly in blood (85%), and antiviral responses to oseltamivir appeared less pronounced.

Conclusions

These observations confirm the association of viral load with outcome of human H5N1 infections and suggest potential differences in virulence and antiviral responses to oseltamivir that may explain the exceptionally high mortality related to clade 2.1 H5N1 infections in Indonesia.
Risk for Tympanic Membrane Perforation After Quinolone Ear Drops for Acute Otitis Externa
Authors: Wang Xi , Winterstein Almut G , Alrwisan Adel , Antonelli Patrick J
Published: April 2019

Background

This study examined whether the use of quinolone ear drops increased the risk of perforation with intact tympanic membranes and acute otitis externa (AOE).

Methods

This was a retrospective cohort study using Medicaid clinical encounter and pharmacy billing records from 1999 through 2010. Children and adults had to have 24 months continuous enrollment in Medicaid prior to the first antibiotic ear drop dispensing (index date), and they had to maintain their enrollment for at least 18 months thereafter. Included ear drops were ofloxacin, ciprofloxacin plus hydrocortisone, ciprofloxacin plus dexamethasone, and neomycin plus hydrocortisone. Tympanic membrane perforation (TMP) was identified as 2 inpatient or outpatient encounters associated with TMP diagnosis at least 30 days apart. A Cox regression model adjusting for patient demographics, calendar year, and the number of ear drop prescriptions was used to compare TMP risk between quinolone and neomycin-exposed patients.

Results

A total of 94 333 patients entered the study cohort. Use of quinolone ear drops was associated with increased risk for TMP compared with neomycin plus hydrocortisone, with an adjusted hazard ratio of 2.26 (95% confidence interval [CI], 1.34–3.83). Adjusted hazard ratios were 2.53 (95% CI, 1.27–5.05) for ofloxacin, 2.24 (95% CI, 1.03–4.85) for ciprofloxacin plus hydrocortisone, and 2.30 (95% CI, 1.09–4.87) for ciprofloxacin plus dexamethasone. Sensitivity analyses were consistent with the primary analysis.

Conclusions

Use of quinolone ear drops to treat AOE is associated with a previously unreported increased risk of developing TMPs. Selection of otic preparations to treat self-limited conditions with intact tympanic membranes should consider TMP risk.
Faecal Proteases from Pouchitis Patients Activate Protease Activating Receptor-2 to Disrupt the Epithelial Barrier
Authors: Hoffman Sarit , Aviv Cohen Nathaniel , Carroll Ian M , Tulchinsky Hagit , Borovok Ilya , Dotan Iris , Maharshak Nitsan
Published: April 2019

Background and Aims

The pathogenesis of pouch inflammation may involve epithelial barrier disruption. We investigated whether faecal proteolytic activity is increased during pouchitis and results in epithelial barrier dysfunction through protease activating receptor [PAR] activation, and assessed whether the intestinal microbiome may be the source of the proteases.

Methods

Faecal samples were measured for protease activity using a fluorescein isothiocyanate [FITC]-casein florescence assay. Caco-2 cell monolayers were exposed to faecal supernatants to assess permeability to FITC-dextran. Tight junction protein integrity and PAR activation were assessed by immunoblot and immunofluorescence. A truncated PAR2 protein in Caco-2 cells was achieved by stable transfection using CRISPR/Cas9 plasmid. PAR2 activation in pouch biopsies was examined using antibodies directed to the N-terminus of the protein. Microbial composition was analysed based on 16S rRNA gene sequence analysis.

Results

Ten pouchitis patients, six normal pouch [NP] patients and nine healthy controls [HC] were recruited. The pouchitis patients exhibited a 5.19- and 5.35-fold higher faecal protease [FP] activity [p ≤ 0.05] compared to the NP and HC participants, respectively. The genus Haemophilus was positively associated with FP activity [R = 0.718, false discovery rate < 0.1]. Faecal supernatants from pouchitis patients activated PAR2 on Caco-2 monolayers, disrupted tight junction proteins and increased epithelial permeability. PAR2 truncation in Caco-2 abrogated faecal protease-mediated permeability. Pouch biopsies obtained from pouchitis patients, but not from NP patients, displayed PAR2 activation.

Conclusions

Protease-producing bacteria may increase faecal proteolytic activity that results in pouch inflammation through disruption of tight junction proteins and increased epithelial permeability in a PAR2-dependent manner. This mechanism may initiate or propagate pouch inflammation.
Sugar enhances outer membrane fusion in Deinococcus grandis spheroplasts to generate calcium ion-dependent extra-huge cells
Authors: Nishino Koki , Tsuchikado Rintaro , Nishida Hiromi
Published: April 2019

In our previous study, we showed that cell fusion occurred in spheroplasts of Deinococcus grandis at 200 mM calcium chloride in the incubation medium. Extra-huge cells (> 0.1 mm in diameter) were observed at this concentration with a low frequency of appearance. In this study, we showed that cell fusion occurred consecutively in D. grandis spheroplasts following an incubation for spheroplast enlargement using medium containing 16.2 mM calcium chloride and 333 mM sucrose. As a result, more extra-huge cells were generated, where cells had maximum diameter of > 1 mm. They can be observed with naked eyes in the incubation medium. The giant cells contained multiple cytoplasms covered by the plasma membrane, indicating that the cell fusion occurred only among the outer membranes. Thus, only the outer membrane and the periplasmic space are shared but not the cytoplasm, indicating that genome of each cell remains in its cytoplasm. Our findings indicate that sugar enhances outer membrane fusion in D. grandis spheroplasts to generate calcium ion-dependent extra-huge cells.
A Physical Model Approach to Gecko Adhesion Opportunity and Constraint: How Rough Could It Be?
Authors: Niewiarowski Peter H , Dhinojwala Ali , Garner Austin M
Published: April 2019

It has been nearly 20 years since Autumn and colleagues established the central role of van der Waals intermolecular forces in how geckos stick. Much has been discovered about the structure and function of fibrillar adhesives in geckos and other taxa, and substantial success has been achieved in translating natural models into bioinspired synthetic adhesives. Nevertheless, synthetics still cannot match the multidimensional performance observed in the natural gecko system that is simultaneously robust to dirt and water, resilient over thousands of cycles, and purportedly competent on surfaces that are rough at drastically different length scales. Apparent insensitivity of adhesion to variability in roughness is particularly interesting from both a theoretical and applied perspective. Progress on understanding the extent to which and the basis of how the gecko adhesive system is robust to variation in roughness is impeded by the complexity of quantifying roughness of natural surfaces and a dearth of data on free-ranging gecko substrate use. Here we review the main challenges in characterizing rough surfaces as they relate to collecting relevant estimates of variation in gecko adhesive performance across different substrates in their natural habitats. In response to these challenges, we propose a practical protocol (borrowing from thermal biophysical ecological methods) that will enable researchers to design detailed studies of structure–function relationships of the gecko fibrillar system. Employing such an approach will help provide specific hypotheses about how adhesive pad structure translates into a capacity for robust gecko adhesion across large variation in substrate roughness. Preliminary data we present on this approach suggest its promise in advancing the study of how geckos deal with roughness variation. We argue and outline how such data can help advance development of design parameters to improve bioinspired adhesives based on the gecko fibrillar system.
Infection Outcomes are Robust to Thermal Variability in a Bumble Bee Host–Parasite System
Authors: Tobin Kerrigan B , Calhoun Austin C , Hallahan Madeline F , Martinez Abraham , Sadd Ben M
Published: April 2019

Climate change-related increases in thermal variability and rapid temperature shifts will affect organisms in multiple ways, including imposing physiological stress. Furthermore, the effects of temperature may alter the outcome of biotic interactions, such as those with pathogens and parasites. In the context of host–parasite interactions, the beneficial acclimation hypothesis posits that shifts away from acclimation or optimum performance temperatures will impose physiological stress on hosts and will affect their ability to resist parasite infection. We investigated the beneficial acclimation hypothesis in a bumble bee–trypanosome parasite system. Freshly emerged adult worker bumble bees, Bombus impatiens, were acclimated to 21, 26, or 29°C. They were subsequently experimentally exposed to the parasite, Crithidia bombi, and placed in a performance temperature that was the same as the acclimation temperature (constant) or one of the other temperatures (mismatched). Prevalence of parasite transmission was checked 4 and 6 days post-parasite exposure, and infection intensity in the gut was quantified at 8 days post-exposure. Parasite strain, host colony, and host size had significant effects on transmission prevalence and infection load. However, neither transmission nor infection intensity were significantly different between constant and mismatched thermal regimes. Furthermore, acclimation temperature, performance temperature, and the interaction of acclimation and performance temperatures had no significant effects on infection outcomes. These results, counter to predictions of the beneficial acclimation hypothesis, suggest that infection outcomes in this host–parasite system are robust to thermal variation within typically experienced ranges. This could be a consequence of adaptation to commonly experienced natural thermal regimes or a result of individual and colony level heterothermy in bumble bees. However, thermal variability may still have a detrimental effect on more sensitive stages or species, or when extreme climatic events push temperatures outside of the normally experienced range.
Treatment duration of pivmecillinam in men, non-pregnant and pregnant women for community-acquired urinary tract infections caused by Escherichia coli: a retrospective Danish cohort study
Authors: Boel Jonas Bredtoft , Jansåker Filip , Hertz Frederik Boëtius , Hansen Katrine Hartung , Thønnings Sara , Frimodt-Møller Niels , Knudsen Jenny Dahl
Published: April 2019

Objectives

To evaluate the importance of treatment duration for therapeutic efficacy of pivmecillinam for community-acquired urinary tract infections (UTIs) caused by Escherichia coli.

Methods

A retrospective cohort study was conducted between 1 January 2010 and 30 September 2016 in adults with community-acquired E. coli bacteriuria, treated empirically with pivmecillinam. Regimens of 3, 5 and 7 days were compared using clinical treatment failure (i.e. redemption of a new antibiotic or hospitalization due to UTI) within 14 and 30 days as outcome. HR and risk difference with 95% CI were estimated for treatment failure. Results were stratified by age (18–50, 51–70, >70 years) and sex.

Results

Of the 21864 cases of E. coli UTI that were analysed, 2524 (11.5%) were in men. In 954 cases (4.4%) E. coli produced ESBL and 125 (13.1%) of the cases were in men. The 3 day regimen increased the risk of treatment failure for all groups. The risk differences between the 3 and 5 day regimens were <10% for women, but >10% for men. Comparing the 7 day and 5 day regimens, only women aged >50 years demonstrated an increased risk of treatment failure within 14 days with the 5 day regimen, but not within 30 days.

Conclusions

With the current data, where data on clinical classification of the E. coli UTI were missing, a 5 day treatment with pivmecillinam at 400 mg three times daily seems to be the rational recommendation for lower UTI in men, pregnant women and women >50 years old. A 3 day regimen seems sufficient for non-pregnant women <50 years old.
Evidence-Based Approaches to HIV-Positive Sexual Minority Men’s Sexual Health
Authors: Harkness Audrey , Safren Steven A.
Published: April 2019

This chapter reviews the current state of research and theory regarding evidence-based sexual health interventions for HIV-positive sexual minority men. Among HIV-positive sexual minority men, sexual health promotion includes reducing sexual behavior that could lead to HIV transmission, increasing adherence to antiretroviral treatment (ART) medication to attain viral load suppression, and addressing psychosocial and contextual factors that impact both of these health behaviors. The chapter reviews evidence-based behavioral approaches to promote sexual minority men’s sexual health, including those focused on increasing condom use, reducing sexual risk, and improving communication about HIV status. It also discusses interventions to improve ART adherence, which promote HIV-positive sexual minority men’s personal health and serve as a secondary prevention intervention via reducing transmissibility. The chapter concludes with an illustration of an evidence-based intervention with an HIV-positive client. Overarching clinical implications and areas for future research regarding HIV-positive sexual minority men’s sexual health are also discussed.
The Role of the Courts in Supporting Therapeutic Interventions
Authors: Bala Nicholas , Slabach Marjorie A.
Published: April 2019

This chapter discusses the role of the family courts and lawyers in supporting, and in some situations limiting, the types of interventions that can be provided to children and their parents in high conflict coparenting cases. It is essential to have collaboration and communication between the judges, lawyers, and mental health professionals if there are to be healthy child outcomes. Increasingly, family judges recognize they have a responsibility not only to resolve disputes between parents, but also to protect the interests of their children, and to encourage a settlement if this is reasonably possible, as well as to hold parents accountable, if they fail to meaningfully engage in court-ordered interventions or parenting arrangements. There are a variety of ways that judges involve mental health professionals to help address family problems, including directing parents to mediation, parenting education, or family or individual therapy, or by appointing a mental health professional undertake an evaluation of a family and report to the court and the parties.
Specialized Child and Family Interventions
Authors: Lebow Jay
Published: April 2019

This chapter reviews strategies that are relevant to intervention with families involved in high conflict divorce. At the center of this approach is a steady patient approach based in constructing realistic proximate goals for treatment in the context of what typically are contentious conflicts. Accent is both on engaging common factors and specific strategies in an integrative systemic framework that may involve meetings with adults and/and children, in various configurations depending on the presenting situation. The chapter brings into this context interventions and research that do not always reach child custody professionals, as well as approaches designed specifically for this population.
Parenting Coordination
Authors: Fidler Barbara J. , Greenberg Lyn R.
Published: April 2019

Parenting coordination is a dispute resolution process generally occurring after a parenting plan has been established, to assist parents in chronic high conflict coparenting. Mental health professionals and family law professionals provide parenting coordination to assist coparents to implement their previously agreed to or court-ordered parenting plan in a child-focused and expeditious manner to minimize parental conflict, thereby reducing risk to children. This chapter summarizes the parenting coordinator’s mandate (education, conflict resolution, case management, decision-making), identifies risks and benefits, and addresses considerations when intimate partner violence (IPV) is a factor. The parenting coordination process from start to finish is discussed—managing referrals, screening for IPV, risk factors, and suitability; conducting the informed consent process; intake and information gathering; consensus-building phase (conflict management, resolution, and negotiation) and decision-making (arbitration). Parenting coordination is not a panacea for all high conflict coparenting situations. Inappropriate cases are identified and guidelines, professional standards, and training requirements are summarized.
Understanding and Using Activities
Authors: Austin David R. , Greenberg Lyn R.
Published: April 2019

Although often overlooked in the context of adult conflict, children’s recreational activities often play an important role in development and adjustment. Appropriately chosen and structured activities promote prosocial and healthy coping behavior, provide models for healthy interaction, facilitate mastery and self-esteem, and provide resources for coping with trauma and stress and resolving psychological and family dysfunction. This chapter draws on relevant research and professional literature from recreational therapy, child development, and the various social science disciplines relevant to court-involved families, providing an overview of relevant findings and concepts and a model for adapting and applying methods derived from recreational therapy to court-involved families. The chapter provides guidance for understanding, selecting, and structuring activities to support early intervention and treatment planning, as well as issues to consider in assessing whether an existing activity is being appropriately utilized for the child and family’s benefit or misused to prevent resolution of problems.
Bringing the Previously Absent Father into the Family
Authors: Pruett Kyle D. , Kline-Pruett Marsha , Deutsch Robin
Published: April 2019

Many fathers—married, never married, or divorced—are absent or remote from their child’s life during the early years. As circumstances change, he may become eager to get to know the child, especially as milestones come and go, or wish to parent after returning from an absence. Mothers are frequently less sanguine about such returns to the child’s life for myriad reasons. This chapter discusses the deleterious effects of father absence on child development, interventions currently in use to reintegrate the positively engaged father back into the family, examining and softening maternal gatekeeping, and the theoretical and evidence bases for such interventions. A case example will be used to demonstrate how the intervention work can be approached to maximize the child’s opportunity to have a positive relationship with his or her father while maintaining equilibrium in the mother–child dyad.
Handbook of Positive Body Image and Embodiment
Authors: Piran Niva
Published: April 2019

Positive body image entails appreciating, loving, respecting, nurturing, protecting, and seeing beauty in the body regardless of its consistency with media appearance ideals. Embodiment reflects a connection between the mind and the body, which have a continual dialectical relationship with the world, and includes positive body connection, body agency and functionality, attuned self-care, positive experiences with body desires, and living in the body as a subjective rather than objectified site. This 38-chapter handbook reviews current knowledge of positive body image and embodiment, as well as future directions for work in these areas, which will be useful for mental health researchers, practitioners, advocates, and activists. Nine chapters review constructs that represent the positive ways we live in our bodies: experiences of embodiment, body appreciation, body functionality, body image flexibility, broad conceptualization of beauty, mindful attunement, intuitive eating, attunement with exercise, and attuned sexuality. Fifteen chapters speak to how we can cultivate positive body image and embodiment by expanding physical freedom (mindful movement, personal safety, connection to agency and desire); mental freedom (resisting objectification, stigma, media images, and gender-related molds); and social power (within families, peers, support systems, and online contexts). Last, 14 chapters address novel ways we can enhance positive body image and embodiment through individual and social interventions that focus on compassion, acceptance, emotional regulation, mindfulness, social justice, movement (yoga), cognitive dissonance, media literacy, and public health and policy initiatives.
Intuitive Eating
Authors: Resch Elyse , Tylka Tracy L.
Published: April 2019

Intuitive eating involves being connected to, trusting in, and responding to the body’s internal hunger and satiety cues. This chapter first details the 10 principles of intuitive eating. Next, the chapter reviews the original and revised Intuitive Eating Scale (the IES and IES-2, respectively), which have been shown to yield reliable and valid scores in samples across different cultures. The chapter then discusses research and interventions on intuitive eating, revealing that it is an adaptive way of eating and living. The chapter ends with seven insights gleaned from intuitive eating research that can be used to situate and guide future investigations. Specifically, intuitive eating is grounded in body acceptance, is dependent on trust in internal body cues, is sabotaged for some individuals, is nurtured in autonomy-supportive environments, is intricately connected to self-compassion, can be taught (even among those with eating disorders), and is not positively associated with overeating.
Cultivating Positive Embodiment Through Peer Connections
Authors: Mafrici Nina
Published: April 2019

Peers represent important transmitters of weight- and body-related norms and ideals. Although much research exists on peer processes that disrupt girls’ and women’s connection to their bodies, this chapter examines the literature specifically pertaining to protective peer influences that support girls and women in distancing from appearance norms and facilitate enhanced connection with their bodies. In this regard, the chapter reviews three domains of protective influences that exist within the peer environment and contribute to positive body image and embodiment. First are peer norms related to (a) body acceptance, (b) distancing from appearance-based comments and comparisons, and (c) alternative norms fostering resiliency from peer appearance-based pressure. Second are interventions designed to support peer groups in resisting and protecting against teasing and harassment. The final domain is initiatives that facilitate activism and empowerment as positive determinants to social power within peer groups. The chapter concludes with a discussion of implications for clinical and prevention initiatives.
Health at Every Size
Authors: LaMarre Andrea , Daníelsdóttir Sigrún
Published: April 2019

Weight-neutral approaches have gained traction over the past decades. These perspectives challenge dominant weight loss paradigms by foregrounding how a focus on health need not be accompanied by an injunction to reduce body size. This chapter explores the roots of the Health at Every Size® (HAES®) paradigm as one weight-neutral approach to positive embodiment. Evidence is reviewed for the effectiveness of HAES, highlighting how it often outperforms weight loss approaches in promoting health and well-being; some recently raised concerns are discussed, including the potential for healthism in an approach that emphasizes health. Finally, it considers how strategies for self-compassion and self-care can be accompanied with parallel efforts to promote social justice for people in all bodies, including bodies marginalized along lines of gender, race, class, ability, and so on. Sustainable gains in promoting positive embodiment must be achieved by advocating for body acceptance at the individual and collective levels.
Behavioral Collaboration and Consultation
Authors: Gormley Matthew J. , Meisinger Rachel E. , Sheridan Susan M.
Published: April 2019

School consultation is a service delivery model that increases the potential of school-based interventionists to provide services to children. This is due to consultation’s indirect nature and emphasis on training consultees. In a consultative model, a consultant (e.g. school psychologist) works with a consultee (e.g. teacher) who will deliver an intervention to a child. The chapter describes the relative advantages of such practices, such as efficiency, improved outcomes for students, enhancement in knowledge of consultees, and fostering of family-school partnerships. The chapter presents a model for behavioral consultation, with considerations that should be made in order to enhance the effectiveness of consultation. In particular, elements of sincerity, trust, communication, and partnership are described. Following, the chapter describes both traditional behavioral consultation and conjoint behavioral consultation.
Reductive Interventions
Authors: Drevon Daniel D. , Hixson Michael D.
Published: April 2019

Schools ordinarily support establishing or increasing target behaviors, for example, increasing the number of letter sounds mastered or the frequency of social initiations; however, supporting the reduction of target behaviors is also an important goal of behavior analytic practice in schools. Although numerous target behaviors may warrant functional assessment and subsequent reduction at the individual level (e.g., aggression, self-injurious behavior), this chapter focuses on describing the implementation of and research outcomes related to reductive interventions designed to help teachers decrease disruptive, inappropriate, off-task, or problem behavior in general education classrooms. Reductive interventions describe strategies that explicitly target reduced levels of a target behavior. These interventions may be implemented to address chronic problem behaviors that may have been unresponsive to other positive interventions. The chapter describes various reductive strategies that may be implemented at a Tier I level, such as time-out, think time, and structured recess.
School-Home Notes and Daily Behavior Report Cards
Authors: Miller Faith G. , Wollersheim-Shervy Sarah , Muldrew Alexandria C.
Published: April 2019

School-Home Note (SHN) and Daily Behavior Report Card (DBRC) programs are a highly effective intervention approach to improving children and adolescents’ behavior at school. These terms, while not exactly synonymous, have both been used in the research literature to describe a similar approach to intervention. That is, SHN and DBRC programs can be thought of as a class of interventions that capitalize on three key elements: (1) providing frequent behavioral feedback, (2) utilizing contingency management procedures, and (3) increasing collaboration between home and school environments. The chapter describes strategies for development and implementation of SHNs and DBRCs, as well as highlighting the use of technology to increase the feasibility of these strategies.
Neural Findings in Pediatric Irritability
Authors: Hirsch Emily , Hulvershorn Leslie
Published: April 2019

Irritability has been conceptualized as a clinical phenomenon that cuts across various psychiatric disorders. Moreover, it is one of the most common reasons that children and adolescents present for mental health treatment. Despite the high prevalence and impairment associated with irritability, until recently, relatively little was known about the brain mechanisms underlying it. Understanding more about the neural mechanisms associated with irritability will likely enhance treatment development. In this chapter, the authors synthesize research that has characterized aspects of irritability in children and adolescents who are typically developing and in those with psychiatric disorders, including severe mood dysregulation (SMD), disruptive mood dysregulation disorder (DMDD), bipolar disorder, and disruptive behavior disorders, as well as attention deficit/hyperactivity disorder and autism, and they suggest future directions for research in this area.
Irritability in Pediatric Psychopathology
Authors: Mazefsky Carla A. , Day Taylor N. , Golt Joshua
Published: April 2019

Irritability is a common presenting concern in youth with autism spectrum disorder (ASD). This chapter provides an overview of research on irritability in ASD, including informative findings from the related fields of temperament and emotion regulation. The developmental course is described, highlighting irritability as one of the earliest phenotypic characteristics in ASD. ASD-related characteristics that may predispose youth with ASD to experience high or chronic irritability are considered, in addition to conceptualizations of irritability in ASD as resulting from a co-occurring psychiatric disorder. Common approaches to assessment, psychosocial treatment, and pharmacologic management of irritability are summarized. Finally, gaps in our understanding of irritability in ASD are highlighted and promising directions for future research are provided.
Are You Paying Attention?
Authors: Raz Amir , Rabipour Sheida
Published: April 2019

“Are you paying attention” addresses the topic of maintaining focus on tasks. The chapter defines attention, offering a solid understanding of the cognitive functions that are often taken for granted. It looks at the idea that multitasking compromises our attention capacity, citing John Ratey of Harvard University, who refers to this craving for stimulation as “acquired attention deficit disorder.” This chapter also addresses clinical impairments in attention and how brain training can make the difference between frustration and accomplishment at work, or peer-rejection and social triumph.
Training the Aging Brain
Authors: Raz Amir , Rabipour Sheida
Published: April 2019

“Training the Aging Brain: Is Cognitive Decline Inevitable?” asks whether cognitive decline necessarily occurs as we age. The answer to this question depends on perspective. To this end, this chapter presents the impressions of a few leading experts along with the latest scientific insights on training and preserving function in the senescent brain. It concludes with a summary of the factors that experts agree play a role in the conundrum of whether cognitive decline accompanies age.
Mental and Neurological Remediation
Authors: Raz Amir , Rabipour Sheida
Published: April 2019

“Mental and Neurological Remediation” outlines some of the emerging approaches to easing the symptoms of developmental conditions, including autism spectrum disorder, attention deficit hyperactivity disorder, and Tourette’s syndrome, as well as disorders that tend to occur later in life, from depression and bipolar disorder to schizophrenia and substance abuse. It goes on to discuss the emergence of brain training in mental health—including concerns pertaining to medication as a primary treatment option, particularly in children.
An Analysis of Orthopedic Surgical Procedures Performed During U.S. Combat Operations from 2002 to 2016
Authors: Stern Caryn A , Stockinger Zsolt T , Todd William E , Gurney Jennifer M
Published: April 2019

Introduction

Orthopedic surgery constitutes 27% of procedures performed for combat injuries. General surgeons may deploy far forward without orthopedic surgeon support. This study examines the type and volume of orthopedic procedures during 15 years of combat operations in Iraq and Afghanistan.

Materials and Methods

Retrospective analysis of the US Department of Defense Trauma Registry (DoDTR) was performed for all Role 2 and Role 3 facilities, from January 2002 to May 2016. The 342 ICD-9-CM orthopedic surgical procedure codes identified were stratified into fifteen categories, with upper and lower extremity subgroups. Data analysis used Stata Version 14 (College Station, TX).

Results

A total of 51,159 orthopedic procedures were identified. Most (43,611, 85.2%) were reported at Role 3 s. More procedures were reported on lower extremities (21,688, 57.9%). Orthopedic caseload was extremely variable throughout the 15-year study period.

Conclusions

Orthopedic surgical procedures are common on the battlefield. Current dispersed military operations can occur without orthopedic surgeon support; general surgeons therefore become responsible for initial management of all injuries. Debridement of open fracture, fasciotomy, amputation and external fixation account for 2/3 of combat orthopedic volume; these procedures are no longer a significant part of general surgery training, and uncommonly performed by general/trauma surgeons at US hospitals. Given their frequency in war, expertise in orthopedic procedures by military general surgeons is imperative.
The Mental Affordance Hypothesis
Authors: McClelland Tom
Published: April 2019

Our successful engagement with the world is plausibly underwritten by our sensitivity to affordances in our immediate environment. The considerable literature on affordances focuses almost exclusively on affordances for bodily actions such as gripping, walking or eating. I propose that we are also sensitive to affordances for mental actions such as attending, imagining and counting. My case for this ‘Mental Affordance Hypothesis’ is motivated by a series of examples in which our sensitivity to mental affordances mirrors our sensitivity to bodily affordances. Specifically, subjects perceive opportunities to perform a mental action and their doing so leads, under the right conditions, to the automatic preparation of that action. I conclude by sketching a mental affordance research program that would reinforce my case for the Mental Affordance Hypothesis and establish its ramifications for a number of debates across philosophy and psychology.
Real-time analysis of single influenza virus replication complexes reveals large promoter-dependent differences in initiation dynamics
Authors: Robb Nicole C , te Velthuis Aartjan J W , Fodor Ervin , Kapanidis Achillefs N
Published: April 2019

The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; further, little is known about cRNA promoter conformations. To probe the RNA conformations adopted during initial replication, we monitored single, surface-immobilized vRNA and cRNA initiation complexes in real-time. Our results show that, while the 3′ terminus of the vRNA promoter exists in dynamic equilibrium between pre-initiation and initiation conformations, the cRNA promoter exhibited very limited dynamics. Two residues in the proximal 3′ region of the cRNA promoter (residues absent in the vRNA promoter) allowed the cRNA template strand to reach further into the active site, limiting promoter dynamics. Our results highlight promoter-dependent differences in influenza initiation mechanisms, and advance our understanding of virus replication.
c-MYC empowers transcription and productive splicing of the oncogenic splicing factor Sam68 in cancer
Authors: Caggiano Cinzia , Pieraccioli Marco , Panzeri Valentina , Sette Claudio , Bielli Pamela
Published: April 2019

The splicing factor Sam68 is upregulated in many human cancers, including prostate cancer (PCa) where it promotes cell proliferation and survival. Nevertheless, in spite of its frequent upregulation in cancer, the mechanism(s) underlying its expression are largely unknown. Herein, bioinformatics analyses identified the promoter region of the Sam68 gene (KHDRBS1) and the proto-oncogenic transcription factor c-MYC as a key regulator of Sam68 expression. Upregulation of Sam68 and c-MYC correlate in PCa patients. c-MYC directly binds to and activates the Sam68 promoter. Furthermore, c-MYC affects productive splicing of the nascent Sam68 transcript by modulating the transcriptional elongation rate within the gene. Importantly, c-MYC-dependent expression of Sam68 is under the tight control of external cues, such as androgens and/or mitogens. These findings uncover an unexpected coordination of transcription and splicing of Sam68 by c-MYC, which may represent a key step in PCa tumorigenesis.
Posterior Petrosal Transotic Approach for Cerebellopontine Angle Hemangioblastoma: Technical Case Report
Authors: Mooney Michael A , Cavallo Claudio , Belykh Evgenii , Gandhi Sirin , Mascitelli Justin , Preul Mark C , Stevens Shawn , Almefty Kaith K , Lawton Michael T
Published: April 2019

BACKGROUND AND IMPORTANCE

Although posterior petrosal approaches are utilized less frequently in many practices today, they continue to provide distinct surgical advantages in carefully selected cases. Here, we report a case of a recurrent cerebellopontine angle (CPA) hemangioblastoma that had failed a prior, more conservative, surgical approach. We provide cadaveric dissections of variations of posterior petrosal approaches to illustrate the advantages of the selected approach.

CLINICAL PRESENTATION

A 70-yr-old female presented with a growing left CPA hemangioblastoma. The lesion had undergone a prior subtotal resection from a retrosigmoid approach and subsequent adjuvant radiation treatment. The patient had worsening left facial strength, progressive balance difficulty, and absent left auditory function. Preoperative angiogram demonstrated arterial blood supply from the left anterior inferior cerebellar artery (AICA) that was deemed unsafe for embolization due to significant arteriovenous shunting. A posterior petrosal transotic approach was performed in order to optimize the working angle to the anterior brainstem and afford the ability to occlude the vascular supply from AICA prior to surgical resection of the lesion.

CONCLUSION

The posterior petrosal transotic approach offers an improved surgical working angle to the anterior brainstem compared to the translabyrinthine approach. This advantage can be particularly important with vascular tumors that receive blood supply anteriorly, as in this case from AICA, and can improve the safety of the resection.
Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sjögren’s syndrome is associated with processes at the centre of their function
Authors: Hillen Maarten R , Chouri Eleni , Wang Maojie , Blokland Sofie L M , Hartgring Sarita A Y , Concepcion Arno N , Kruize Aike A , Burgering Boudewijn M T , Rossato Marzia , van Roon Joel A G , Radstake Timothy R D J
Published: April 2019

Objective

A considerable body of evidence supports a role for type-I IFN in the pathogenesis of primary SS (pSS). As plasmacytoid dendritic cells (pDCs) are a major source of type-I IFN, we investigated their molecular regulation by measuring expression of a large set of miRNAs.

Methods

pDCs were isolated from peripheral blood of pSS patients (n = 30) and healthy controls (n = 16) divided into two independent cohorts (discovery and replication). Screening of 758 miRNAs was assessed by an OpenArray quantitative PCR-based technique; replication of a set of identified miRNAs was performed by custom array. Functional annotation of miRNA targets was performed using pathway enrichment. Novel targets of miR-29a and miR-29c were identified using a proteomic approach (stable isotope labelling with amino acids in cell culture).

Results

In the discovery cohort, 20 miRNAs were differentially expressed in pSS pDCs compared with healthy control pDCs. Of these, differential expression of 10 miRNAs was confirmed in the replication cohort. The dysregulated miRNAs were involved in phosphoinositide 3-kinase-Ak strain transforming and mammalian target of rapamycin signalling, as well as regulation of cell death. In addition, a set of novel protein targets of miR-29a and miR-29c were identified, including five targets that were regulated by both miRs.

Conclusion

The dysregulated miRNome in pDCs of patients with pSS is associated with aberrant regulation of processes at the centre of pDC function, including type-I IFN production and cell death. As miR-29a and miR-29c are pro-apoptotic factors and several of the novel targets identified here are regulators of apoptosis, their downregulation in patients with pSS is associated with enhanced pDC survival.
Applications of Tranexamic acid in benign gynecology
Authors: Klebanoff Jordan S. , Marfori Cherie Q. , Ingraham Caitlin F. , Wu Catherine Z. , Moawad Gaby N.
Published: April 2019

Purpose of review

Bleeding at the time of benign gynecologic surgery, as well as from benign gynecologic conditions, is a major source of morbidity for many women. Few nonhormonal medical options exist for the treatment of heavy menstrual bleeding, and to reduce surgical bleeding during major gynecologic surgery. Interest in Tranexamic acid (TXA) as a means to reduce surgical blood loss has been growing across many surgical specialties. This review focuses on applications for TXA as a means to reduce heavy menstrual bleeding (HMB) as well as to reduce surgical bleeding during benign gynecologic surgery.

Recent findings

Tranexamic acid is an effective treatment to reduce the volume of bleeding during menstruation. Tranexamic acid was found to be superior to both placebo and oral progestins, and as good as combined oral contraceptives at reducing menstrual blood volume. Tranexamic acid has also been show to reduce the volume of bleeding during abdominal myomectomy as well as hysterectomy. There is a major need for prospective studies evaluating the utility of TXA for reducing blood loss during benign gynecologic surgery.

Tranexamic acid has been found to be an excellent affordable nonhormonal treatment option for women with HMB and should be considered during major gynecologic surgery.
Partner status moderates the relationships between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy
Authors: Dorfman Caroline S. , Arthur Sarah S. , Kimmick Gretchen G. , Westbrook Kelly W. , Marcom Paul Kelly , Corbett Cheyenne , Edmond Sara N. , Shelby Rebecca A.
Published: April 2019

Objective:

Past studies indicate that >90% of breast cancer survivors taking adjuvant endocrine therapy (AET) experience menopausal symptoms including sexual problems (eg, vaginal dryness, dyspareunia); however, research examining the impact of these problems on quality-of-life is limited. This cross-sectional study examined (1) the impact of sexual problems and self-efficacy for coping with sexual problems (sexual self-efficacy) on quality-of-life (ie, psychosocial quality-of-life and sexual satisfaction), and (2) partner status as a moderator of these relationships.

Methods:

Postmenopausal breast cancer survivors taking AET completed measures of sexual problems (Menopause-Specific Quality-of-Life [MENQOL] sexual subscale], sexual self-efficacy, psychosocial quality-of-life (MENQOL psychosocial subscale), and sexual satisfaction (Functional Assessment of Cancer Therapy-General item).

Results:

Bivariate analyses showed that women reporting greater sexual problems and lower sexual self-efficacy had poorer quality-of-life and less sexual satisfaction (all P-values < 0.05). Partner status moderated the relationship between sexual problems and psychosocial quality-of-life (P = 0.02); at high levels of sexual problems, unpartnered women experienced poorer psychosocial quality-of-life than partnered women. Partner status also moderated the relationship between self-efficacy and psychosocial quality-of-life (P = 0.01). Self-efficacy was unrelated to psychosocial quality-of-life for partnered women; for unpartnered women, low self-efficacy was associated with poorer quality-of-life. Partner status did not moderate the relationships between sexual problems or self-efficacy with sexual satisfaction.

Conclusions:

Greater sexual problems and lower sexual self-efficacy were associated with poorer psychosocial quality-of-life and sexual satisfaction among postmenopausal breast cancer survivors taking AET. Interventions to address sexual problems and sexual self-efficacy, particularly among unpartnered women, may be beneficial for improving the well-being of postmenopausal breast cancer survivors on AET.
Confirmatory factor analysis of the Insomnia Severity Index (ISI) and invariance across race: a pooled analysis of MsFLASH data
Authors: Otte Julie L. , Bakoyannis Giorgos , Rand Kevin L. , Ensrud Kristine E. , Guthrie Katherine A. , Joffe Hadine , McCurry Susan M. , Newton Kathrine M. , Carpenter Janet S.
Published: April 2019

Objective:

Women's sleep at menopause is widely reported to be problematic. The Insomnia Severity Index (ISI) is a commonly used tool for quantifying sleep problems in clinical and research settings, but psychometric properties in postmenopausal women have not been reported. Our study aim was to examine the factor structure of the ISI in a large and diverse sample of midlife women with hot flashes.

Methods:

Baseline data were from 899 women enrolled in one of the three clinical trials using similar entry criteria conducted by the Menopause Strategies Finding Lasting Answers to Symptoms and Health research network. We conducted confirmatory factor analyses for the total sample and within strata defined by race/ethnicity (black and white women).

Results:

The ISI had two factors in the total sample. The two-factor structure was consistent across black and white women, with the exception of one item “difficulty falling asleep.”

Conclusions:

The ISI in midlife women with hot flashes is composed of two factors that capture dimensions of the insomnia severity and daytime impact. The instrument is a psychometrically sound scale appropriate for use in research and clinical practice to capture the severity and daytime impact of insomnia symptoms in diverse samples of midlife women with hot flashes. An abbreviated screening of two items could be considered to determine if further evaluation is needed of sleep complaints.