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.

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.

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.

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.

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.

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.

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.

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.

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.

Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.

The superficial bladder epithelium is a powerful barrier to urine and also serves as a regulator of bladder volume, which is achieved by apical exocytosis of specialized fusiform vesicles during distension of the bladder. We report that type 1 fimbriated uropathogenic Escherichia coli (UPEC) circumvents the bladder barrier by harboring in these Rab27b/CD63-positive and cAMP-regulatable fusiform vesicles within bladder epithelial cells (BECs). Incorporation of UPEC into BEC fusiform compartments enabled bacteria to escape elimination during voiding and to re-emerge in the urine as the bladder distended. Notably, treatment of UPEC-infected mice with a drug that increases intracellular cAMP and induces exocytosis of fusiform vesicles reduced the number of intracellular E. coli.

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.

Mental health of Australian Aboriginal women during pregnancy: identifying the gaps.

Despite Australia's high standard of health care provision, Australian Aboriginal women continue to experience poor pregnancy outcomes in terms of maternal and foetal morbidity and mortality. In an attempt to improve these outcomes, health care providers have developed targeted antenatal programmes that aim to address identified health behaviours that are known to contribute to poor health during pregnancy. While some areas of improvement have been noted in rates of engagement with health services, the rates of premature births and low birth weight babies continue to be significantly higher than in the non-Aboriginal population. It appears that Australian researchers have been focused on the behaviour of the individual and have failed to fully consider the impact that social and emotional well-being has on both health behaviours and pregnancy outcomes. This review has highlighted the need for an approach to both research and clinical practice that acknowledges the Aboriginal view of health which encompasses mental, physical, cultural and spiritual health. Until clinicians and Aboriginal women have a shared understanding of how social and emotional well-being is experienced by Aboriginal women, in other words their explanatory model, it is unlikely that any meaningful improvements will be seen.

TLR4-mediated expulsion of bacteria from infected bladder epithelial cells.

Uropathogenic Escherichia coli invade bladder epithelial cells (BECs) by direct entry into specialized cAMP regulated exocytic compartments. Remarkably, a significant number of these intracellular bacteria are subsequently expelled in a nonlytic and piecemeal fashion by infected BECs. Here, we report that expulsion of intracellular E. coli by infected BECs is initiated by the pattern recognition receptor, Toll-like receptor (TLR)4, after activation by LPS. Also, we reveal that caveolin-1, Rab27b, PKA, and MyRIP are components of the exocytic compartment, and that they form a complex involved in the exocytosis of bacteria. This capacity of TLR4 to mediate the expulsion of intracellular bacteria from infected cells represents a previously unrecognized function for this innate immune receptor.

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.

Spatial tuning to sound-source azimuth in the inferior colliculus of unanesthetized rabbit.

Despite decades of research devoted to the study of inferior colliculus (IC) neurons' tuning to sound-source azimuth, there remain many unanswered questions because no previous study has examined azimuth tuning over a full range of 360° azimuths at a wide range of stimulus levels in an unanesthetized preparation. Furthermore, a comparison of azimuth tuning to binaural and contralateral ear stimulation over ranges of full azimuths and widely varying stimulus levels has not previously been reported. To fill this void, we have conducted a study of azimuth tuning in the IC of the unanesthetized rabbit over a 300° range of azimuths at stimulus levels of 10-50 dB above neural threshold to both binaural and contralateral ear stimulation using virtual auditory space stimuli. This study provides systematic evidence for neural coding of azimuth. We found the following: 1) level-tolerant azimuth tuning was observed in the top 35% regarding vector strength and in the top 15% regarding vector angle of IC neurons; 2) preserved azimuth tuning to binaural stimulation at high stimulus levels was created as a consequence of binaural facilitation in the contralateral sound field and binaural suppression in the ipsilateral sound field; 3) the direction of azimuth tuning to binaural stimulation was primarily in the contralateral sound field, and its center shifted laterally toward -90° with increasing stimulus level; 4) at 10 dB, azimuth tuning to binaural and contralateral stimulation was similar, indicating that it was mediated by monaural mechanisms; and 5) at higher stimulus levels, azimuth tuning to contralateral ear stimulation was severely degraded. These findings form a foundation for understanding neural mechanisms of localizing sound-source azimuth.

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.

The role of anthrolysin O in gut epithelial barrier disruption during Bacillus anthracis infection.

Gastrointestinal (GI) anthrax, caused by the bacterial infection of Bacillus anthracis, posts a significant bioterrorism threat by its relatively high mortality rate in humans. Different from inhalational anthrax by the route of infection, accumulating evidence indicates the bypass of vegetative bacteria across GI epithelium is required to initiate GI anthrax. Previously, we reported that purified anthrolysin O (ALO), instead of tripartite anthrax edema and lethal toxins, is capable of disrupting gut epithelial tight junctions and barrier function in cultured cells. Here, we show that ALO can disrupt intestinal tissue barrier function in an ex vivo mouse model. To explore the effects of ALO in a cell culture model of B. anthracis infection, we showed that anthrax bacteria can effectively reduce the monolayer integrity of human Caco-2 brush-border expressor (C2BBE) cells based on the reduced transepithelial resistance and the increased leakage of fluorescent dye. This disruption is likely caused by tight junction dysfunction observed by the reorganization of the tight junction protein occludin. Consequently, we observe significant passage of vegetative anthrax bacteria across C2BBE cells. This barrier disruption and bacterial crossover requires ALO since ALO-deficient B. anthracis strains fail to induce monolayer dysfunction and allow the passage of anthrax bacteria. Together these findings point to a pivotal role for ALO within the establishment of GI anthrax infection and the initial bypass of the epithelial barrier.

Lead bioaccumulation in emydid turtles of an urban lake and its relationship to shell disease.

Urban runoff contributes significant amounts of heavy metals into receiving waters in which turtles make up a large portion of the biodiversity. Turtles accumulate heavy metals in their body and shell bone, yet little is known about how it affects their health. Studies in vertebrates have shown bioaccumulation of lead to have several deleterious effects such as immunosuppression, impairment of skeletal calcification and competition with calcium ion uptake. This study surveys the bioaccumulation of lead in emydid turtles of an urban lake and investigates the differences based on species, sex, size and its possible relationship to shell disease. Shell disease was quantified and small sections of shell were collected from each specimen and analyzed for lead content using Graphite Furnace Atomic Adsorption Spectrometry. Significant differences of lead accumulation were found between species, yet not with sex or body size. Linear regression comparison of lead concentration and shell disease showed no positive correlation.

Capturing dynamic processes of change in GROW mutual help groups for mental health.

The need for a model that can portray dynamic processes of change in mutual help groups for mental health (MHGMHs) is emphasized. A dynamic process model has the potential to capture a more comprehensive understanding of how MHGMHs may assist their members. An investigation into GROW, a mutual help organization for mental health, employed ethnographic, phenomenological and collaborative research methods. The study examined how GROW impacts on psychological well being. Study outcomes aligned with the social ecological paradigm (Maton in Understanding the self-help organization: frameworks and findings. Sage, Thousand Oaks 1994) indicating multifactorial processes of change at and across three levels of analysis: group level, GROW program/community level and individual level. Outcome themes related to life skills acquisition and a change in self-perception in terms of belonging within community and an increased sense of personal value. The GROW findings are used to assist development of a dynamic multi-dimensional process model to explain how MHGMHs may promote positive change.