Cryptorchidism Review for the Primary Care Provider.

Cryptorchidism, or undescended testes, is the most common disorder of the genitals seen at birth. Due to its high prevalence and short- and long-term sequelae, it is crucial that primary care providers are familiar with the appropriate management of cryptorchidism. This paper serves to review the embryology, diagnosis, management, and treatment of cryptorchidism with the goal of serving as a valuable reference for providers managing pediatric and neonatal urological issues in the primary care setting, using the American Urological Association's most recent guidelines on the subject. Importantly, it also serves as a review of the long-term consequences of cryptorchidism (even after repair) and reinforces the need for continued surveillance for complications throughout a patient's life.

Isthmoceles: A Growing Concern.

An isthmocele is described as a pouch-like defect in the uterus with a thin roof formed by inadequate healing of the smooth muscle of the anterior uterine wall at the site of a hysterotomy. With increased rates of deliveries by cesarean section, isthmoceles are becoming a more common cause of gynecologic and obstetric complications. Gynecologic issues include pelvic pain, postmenstrual bleeding, and reduced fertility or infertility. Therefore, it is important that providers consider these defects in their differential diagnosis as their presentation can mimic other gynecologic conditions, such as endometriosis. Fortunately, many effective treatment options are available, such as conservative hormonal treatment or surgical repair by laparoscopic, hysteroscopic, or transvaginal methods.

Estimating naloxone need in the USA across fentanyl, heroin, and prescription opioid epidemics: a modelling study.

BACKGROUND: The US overdose crisis is driven by fentanyl, heroin, and prescription opioids. One evidence-based policy response has been to broaden naloxone distribution, but how much naloxone a community would need to reduce the incidence of fatal overdose is unclear. We aimed to estimate state-level US naloxone need in 2017 across three main naloxone access points (community-based programmes, provider prescription, and pharmacy-initiated distribution) and by dominant opioid epidemic type (fentanyl, heroin, and prescription opioid). METHODS: In this modelling study, we developed, parameterised, and applied a mechanistic model of risk of opioid overdose and used it to estimate the expected reduction in opioid overdose mortality after deployment of a given number of two-dose naloxone kits. We performed a literature review and used a modified-Delphi panel to inform parameter definitions. We refined an established model of the population at risk of overdose by incorporating changes in the toxicity of the illicit drug supply and in the naloxone access point, then calibrated the model to 2017 using data obtained from proprietary data sources, state health departments, and national surveys for 12 US states that were representative of each epidemic type. We used counterfactual modelling to project the effect of increased naloxone distribution on the estimated number of opioid overdose deaths averted with naloxone and the number of naloxone kits needed to be available for at least 80% of witnessed opioid overdoses, by US state and access point. FINDINGS: Need for naloxone differed by epidemic type, with fentanyl epidemics having the consistently highest probability of naloxone use during witnessed overdose events (range 58-76% across the three modelled states in this category) and prescription opioid-dominated epidemics having the lowest (range 0-20%). Overall, in 2017, community-based and pharmacy-initiated naloxone access points had higher probability of naloxone use in witnessed overdose and higher numbers of deaths averted per 100 000 people in state-specific results with these two access points than with provider-prescribed access only. To achieve a target of naloxone use in 80% of witnessed overdoses, need varied from no additional kits (estimated as sufficient) to 1270 kits needed per 100 000 population across the 12 modelled states annually. In 2017, only Arizona had sufficient kits to meet this target. INTERPRETATION: Opioid epidemic type and how naloxone is accessed have large effects on the number of naloxone kits that need to be distributed, the probability of naloxone use, and the number of deaths due to overdose averted. The extent of naloxone distribution, especially through community-based programmes and pharmacy-initiated access points, warrants substantial expansion in nearly every US state. FUNDING: National Institute of Health, National Institute on Drug Abuse.

Couples Therapy Delivered Through Videoconferencing: Effects on Relationship Outcomes, Mental Health and the Therapeutic Alliance.

Changing technology, and the pervasive demand created by a greater need in the population for access to mental health interventions, has led to the development of technologies that are shifting the traditional way in which therapy is provided. This study investigated the efficacy of a behavioral couples therapy program conducted via videoconferencing, as compared to face-to-face. There were 60 participants, in couples, ranging in age from 21 to 69 years old. Couples had been in a relationship for between 1 to 49 years. The 30 couples were randomly allocated to the face-to-face or videoconferencing group. They all took part in Couple CARE-a couples behavioral education program which promotes self-change in order to increase relationship satisfaction. The six session manualized intervention was offered in an identical manner to all clients, in each condition. Data analysis was based on several questionnaires completed by each couple at pre, post and 3-months follow-up. Results showed that therapeutic alliance ratings did not differ between groups, but increased significantly over time for both groups. Additionally, the results indicated improvements in relationship satisfaction, mental health, and all other outcome scores over time, which did not differ based on condition. This study uniquely contributes to the literature exploring the use of technology to provide therapy. Specifically, the study provides evidence for couples therapy via videoconferencing as a viable alternative to face-to-face interventions, especially for those couples who may not have access to the treatment they require. It is anticipated that the results of this study will contribute to the field of online therapy, and add to fostering confidence in agencies to allow expansion of services conducted via videoconferencing.

Expectations and Experiences of Couples Receiving Therapy Through Videoconferencing: A Qualitative Study.

Videoconferencing is an emerging medium through which psychological therapy, including relationship interventions for couples, can be delivered. Understanding clients' expectations and experiences of receiving therapy through this medium is important for optimizing future delivery. This study used a qualitative methodology to explore the expectations and experiences of couples throughout the process of the Couple CARE program, which was delivered through videoconferencing. Fifteen couples participated in semi-structured interviews during the first and last sessions of the intervention. The interviews were conducted using the iChat program, with the therapist conducting the first interview and an external interviewer conducting the second. Thematic analysis was used to identify themes from the interview transcripts. Five themes were identified from the pre-therapy interviews, reflecting couples' initial impressions and expectations: new experience, comparison, practical aspects, connection and dynamics, and distance and space. Couples' experiences were explored in the eight themes from the post-therapy interviews: technicalities, the idea of "distance," satisfaction and comfort, confidentiality, comparisons, new experience, expectations change, and working alliance. Overall, the present study found that couples experienced a positive shift in expectations. Despite some initial concerns regarding the therapist's ability to empathize over a screen and the potential for the technology to break down, many clients noted that videoconferencing allowed them to become fully immersed in the therapeutic process. In fact, many couples felt that videoconferencing created an element of 'distance' from the therapist that allowed them to feel a greater sense of control and comfort. Couples consistently described being able to effectively connect with the therapist, and that the video actually enhanced the therapeutic alliance, due to a greater perceived focus on therapy processes. Overall, despite some initial concerns, the majority of couples found the videoconferencing experience to be beneficial and positive.

Highly Diastereoselective Synthesis of a HCV NS5B Nucleoside Polymerase Inhibitor.

An asymmetric synthesis of HCV NS5B nucleoside polymerase inhibitor (1) is described. This novel route features several remarkably diastereoselective and high-yielding transformations, including construction of the all-carbon quaternary stereogenic center at C-2 via a thermodynamic aldol reaction. A subsequent glycosylation reaction with activated uracil via C-1 phosphate and installation of the cyclic phosphate group using an achiral phosphorus(III) reagent followed by oxidation provides 1.

Complete Genome Sequence of a Porcine Polyomavirus from Nasal Swabs of Pigs with Respiratory Disease.

Metagenomic sequencing of pooled nasal swabs from pigs with unexplained respiratory disease identified a large number of reads mapping to a previously uncharacterized porcine polyomavirus. Sus scrofa polyomavirus 2 was most closely related to betapolyomaviruses frequently detected in mammalian respiratory samples.

How Do Our Values Inform Ethical Research? A Narrative of Recognizing Colonizing Practices.

How do you reconcile tensions between ethical research practice, personal values, and disciplinary values? This article focuses on an ethical challenge involving the engagement of rural Indigenous community members that emerged during my PhD fieldwork. The narrative illustrates the necessity to engage in critical reflexive research practice, a process which saw me respond to my own feelings of "wrong" and "right," contemplate a distinction between procedural ethics and virtue ethics in community-based research, explore colonizing research practices, and endeavor to reconcile an instance where the values of community psychology appeared in contest. The "voice" in this narrative is that of the first author; the dual authorship reflects the ongoing collaboration between both authors. When this ethical issue came about, our relationship was one of "student" and "supervisor"; we are now colleagues and friends.

The SAATELLITE and EVADE Clinical Studies Within the COMBACTE Consortium: A Public-Private Collaborative Effort in Designing and Performing Clinical Trials for Novel Antibacterial Drugs to Prevent Nosocomial Pneumonia.

The Innovative Medicines Initiative-funded COMBACTE consortium fosters academic-industry partnership in pioneering studies to combat serious bacterial infections. We describe how this partnership is advancing the development of 2 monoclonal antibodies, MEDI4893 and MEDI3902, for the prevention of nosocomial pneumonia.

Quantitative assessment of insertion sequence impact on bacterial genome architecture.

Insertion sequence (IS) elements are important mediators of genome plasticity and can lead to phenotypic changes with evolutionary significance. In multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, IS elements have contributed significantly to the mobilization of genes that encode resistance to antimicrobial drugs. A systematic analysis of IS elements is needed for a more comprehensive understanding of their evolutionary impact. We developed a computational approach (ISseeker) to annotate IS elements in draft genome assemblies and applied the method to analysis of IS elements in all publicly available A. baumannii(>1000) and K. pneumoniae(>800) genome sequences, in a phylogenetic context. Most IS elements in A. baumanniigenomes are species-specific ISAba elements, whereas K. pneumoniaegenomes contain significant numbers of both ISKpn elements and elements that are found throughout the Enterobacteriaceae. A. baumanniigenomes have a higher density of IS elements than K. pneumoniae, averaging ~33 vs ~27 copies per genome. In K. pneumoniae, several insertion sites are shared by most genomes in the ST258 clade, whereas in A. baumannii, different IS elements are abundant in different phylogenetic groups, even among closely related Global Clone 2 strains. IS elements differ in the distribution of insertion locations relative to genes, with some more likely to disrupt genes and others predominantly in intergenic regions. Several genes and intergenic regions had multiple independent insertion events, suggesting that those events may confer a selective advantage. Genome- and taxon-wide characterization of insertion locations revealed that IS elements have been active contributors to genome diversity in both species.

Intraoperative Parathormone Monitoring Mitigates Age-Related Variability in Targeted Parathyroidectomy for Patients with Primary Hyperparathyroidism.

BACKGROUND: Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. METHODS: A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean -1 standard deviation (SD)], typical (47-73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. RESULTS: Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups (p < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age (p < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI (p < 0.05). CONCLUSIONS: Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration.

Auditory distance coding in rabbit midbrain neurons and human perception: monaural amplitude modulation depth as a cue.

Mechanisms underlying sound source distance localization are not well understood. Here we tested the hypothesis that a novel mechanism can create monaural distance sensitivity: a combination of auditory midbrain neurons' sensitivity to amplitude modulation (AM) depth and distance-dependent loss of AM in reverberation. We used virtual auditory space (VAS) methods for sounds at various distances in anechoic and reverberant environments. Stimulus level was constant across distance. With increasing modulation depth, some rabbit inferior colliculus neurons increased firing rates whereas others decreased. These neurons exhibited monotonic relationships between firing rates and distance for monaurally presented noise when two conditions were met: (1) the sound had AM, and (2) the environment was reverberant. The firing rates as a function of distance remained approximately constant without AM in either environment and, in an anechoic condition, even with AM. We corroborated this finding by reproducing the distance sensitivity using a neural model. We also conducted a human psychophysical study using similar methods. Normal-hearing listeners reported perceived distance in response to monaural 1 octave 4 kHz noise source sounds presented at distances of 35-200 cm. We found parallels between the rabbit neural and human responses. In both, sound distance could be discriminated only if the monaural sound in reverberation had AM. These observations support the hypothesis. When other cues are available (e.g., in binaural hearing), how much the auditory system actually uses the AM as a distance cue remains to be determined.

Imposed identities and limited opportunities: Advocacy agency staff perspectives on the construction of their clients with intellectual disabilities.

Intellectual disability is commonly conceptualised as stigmatised identity; however, within the literature, the notion of a damaged identity is contested. The aim of this research was to explore the social construction of intellectual disability from the perspective of staff who work closely with people with intellectual disabilities. Informed by a contextualist perspective, this research was based on interviews with five staff members of an advocacy agency in a regional area of Australia. Causal layered analysis was used to deconstruct the interview data. Analysis of the interactions that emerged across the causal layers revealed a complex dynamic of world views, which served to dehumanise people with intellectual disabilities and blame them for their own fate (victim blaming). For transformative change to occur, understandings of the 'problems' of intellectual disability must be reformulated and those social structures and processes that support the relationship between the powerful and the powerless must be challenged.

Nail Alterations in Cutaneous T-Cell Lymphoma: A Case Series and Review of Nail Manifestations.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) encompasses a broad range of lymphoproliferative diseases affecting the skin and can be clinically misleading due to its variable presentation. Nail alterations commonly appear in advanced-stage mycosis fungoides and true Sézary syndrome; however, they may be present in any stage of the disease. Although proper recognition of nail involvement in CTCL has both clinical and therapeutic value, specific nail findings have been infrequently described in the current literature. OBSERVATIONS: We describe 4 patients with CTCL who presented with clinically significant nail alterations. The most common findings were nail discoloration, thickening, crumbling, onycholysis, and onychomadesis. Other notable findings included splinter hemorrhages, subungual hyperkeratosis, and anonychia. CONCLUSIONS AND MESSAGE: The described cases illustrate many of the documented nail findings associated with CTCL and emphasize the variable nature of nail manifestations. The presence of specific nail alterations should increase the clinical suspicion of CTCL - especially in patients with concomitant systemic and/or cutaneous manifestations - and early biopsy specimens should be taken for diagnosis. Nail alterations should also be accurately described and monitored in all patients with biopsy-confirmed CTCL to help identify treatment response and detect disease recurrence.

Zinc deficiency induces apoptosis via mitochondrial p53- and caspase-dependent pathways in human neuronal precursor cells.

Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin-µ, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency.

Azimuth and envelope coding in the inferior colliculus of the unanesthetized rabbit: effect of reverberation and distance.

Recognition and localization of a sound are the major functions of the auditory system. In real situations, the listener and different degrees of reverberation transform the signal between the source and the ears. The present study was designed to provide these transformations and examine their influence on neural responses. Using the virtual auditory space (VAS) method to create anechoic and moderately and highly reverberant environments, we found the following: 1) In reverberation, azimuth tuning was somewhat degraded with distance whereas the direction of azimuth tuning remained unchanged. These features remained unchanged in the anechoic condition. 2) In reverberation, azimuth tuning and envelope synchrony were degraded most for neurons with low best frequencies and least for neurons with high best frequencies. 3) More neurons showed envelope synchrony to binaural than to monaural stimulation in both anechoic and reverberant environments. 4) The percentage of envelope-coding neurons and their synchrony decreased in reverberation with distance, whereas it remained constant in the anechoic condition. 5) At far distances, for both binaural and monaural stimulation, the neural gain in reverberation could be as high as 30 dB and as much as 10 dB higher than those in the anechoic condition. 6) The majority of neurons were able to code both envelope and azimuth in all of the environments. This study provides a foundation for understanding the neural coding of azimuth and envelope synchrony at different distances in reverberant and anechoic environments. This is necessary to understand how the auditory system processes "where" and "what" information in real environments.

Dealing with wicked problems: conducting a causal layered analysis of complex social psychological issues.

Causal layered analysis (CLA) is an emerging qualitative methodology adopted in the discipline of planning as an approach to deconstruct complex social issues. With psychologists increasingly confronted with complex, and "wicked" social and community issues, we argue that the discipline of psychology would benefit from adopting CLA as an analytical method. Until now, the application of CLA for data interpretation has generally been poorly defined and overwhelming for the novice. In this paper we propose an approach to CLA that provides a method for the deconstruction and analysis of complex social psychological issues. We introduce CLA as a qualitative methodology well suited for psychology, introduce the epistemological foundations of CLA, define a space for it adoption within the discipline, and, outline the steps for conducting a CLA using an applied example.

Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.

In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO) in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC) mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP) are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior.