Search

International audience; Nuclear deubiquitinase BAP1 (BRCA1-associated protein 1) is a core component of multiprotein complexes that promote transcription by reversing the ubiquitination of histone 2A (H2A). BAP1 is a tumor suppressor whose germline loss-of-function variants predispose to cancer. To our knowledge, there are very rare examples of different germline variants in the same gene causing either a neurodevelopmental disorder (NDD) or a tumor predisposition syndrome. Here, we report a series of 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic NDD. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In matching peripheral blood mononuclear cells, histone H3 K27 acetylation ChIP-seq indicated that these BAP1 variants induced genome-wide chromatin state alterations, with enrichment for regulatory regions surrounding genes of the ubiquitin-proteasome system (UPS). Altogether, these results define a clinical syndrome caused by rare germline missense BAP1 variants that alter chromatin remodeling through abnormal histone ubiquitination and lead to transcriptional dysregulation of developmental genes.

Knowledge of which pulmonary function tests are commonly performed in primary care and interpretation of their results is integral for the diagnosis, care, and management of those with pulmonary symptoms. This article provides an overview of the most common pulmonary function tests and interpretation of their results.

OBJECTIVE To compare postoperative gluteal and posterior thigh pain, device performance, and perioperative complications in women undergoing sacrospinous ligament fixation with an anchor-based compared with a suture-capturing device. METHODS This was a single-center, patient-blinded, parallel, superiority trial of patients undergoing native-tissue pelvic organ prolapse repair through sacrospinous ligament fixation with an anchor-based compared with suture-capturing device using randomized-block randomization. The primary outcome was the increase in gluteal and posterior thigh pain from baseline to 1-week postoperation using the numerical rating scale. Pain was also assessed at postoperative day 1, week 6, and a summarized assessment for the first postoperative week. Intraoperative device performance, home opioid pain medication use, and changes in prolapse symptom scores were also analyzed. To provide 80% power to detect a pain difference of 2.5 points between the groups with an SD of 2.8 and a 15% dropout estimate using a two-sided 5% significance level, 24 patients were required per group. Analysis with Student's t test, Wilcoxon rank-sum tests, and Fisher exact tests were performed as well as an analysis of covariance for the primary outcome. RESULTS Between September 2018 and June 2020, 47 patients (24 anchor-based and 23 suture-capturing) were included in the study. There was no significant difference between the anchor-based and suture-capture groups in mean change in gluteal and posterior thigh pain from baseline to 1-week postoperation (-0.4, 95% CI -1.6 to 2.3). The highest pain increase from baseline during the first postoperative week was also similar between the two groups (up 4.00 and up 4.74, respectively) with no significant difference between the anchor-based and suture-capture groups (-0.7, 95% CI -1.4 to 2.8). There were no differences in changes in pain at any of the other timepoints, in opioid pain medication utilization, device performance, or in prolapse symptom scores. CONCLUSION An anchor-based device did not reduce postoperative gluteal and posterior thigh pain compared with a suture-based device after sacrospinous ligament fixation. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03565640. FUNDING SOURCE Supported by Neomedic via Adler Instruments. Neomedic provided funding for this principal investigator-initiated study. Funding went to providing small value gift cards to patients for study completion, office supplies for the study, and funding the data analysis collaboration with the Wake Forest Baptist Health CTSI Biostatistics Department. Neomedic did not have any direct role in study design, patient recruitment, study execution, data analysis, or manuscript writing or editing.

Ureteral injury during gynecological surgery can be managed in a variety of ways, from endoscopic stent placement to ureteroneocystotomy with accompanying psoas hitch and/or Boari flap. The majority of these occur during hysterectomy; therefore, gynecologic surgeons may not be as familiar with repair in women with intact uteri. Herein we present our technique for delayed robotic-assisted ureteral reimplant and psoas hitch in a woman with a ureteral injury sustained during cesarean section, which initially presented as a uretero-cervical fistula.In this video, we describe the evaluation and surgical management of a patient with delayed recognition of a left distal ureteral injury sustained during cesarean section. We present necessary modifications to robotic-assisted laparoscopic ureteroneocystostomy and psoas hitch to accommodate an intact uterus including the need for uterine manipulation, division of the round ligament, bladder mobilization from the lower uterine segment and development of the retropubic space, reimplantation steps, and psoas hitch.Simple modifications to a traditional technique of robotic-assisted ureteroneocystotomy effectively compensate for the presence of a uterus. Obstetricians should maintain a high index of suspicion for ureteral injury in women with new-onset severe urinary leakage post-cesarean section.

Impetigo, a bacterial skin infection that involves the superficial layers of the skin, is one of the most common skin infections in children ages 2 to 5 but can occur in individuals across the lifespan. This article discusses the diagnosis and management of impetigo in primary care.

Supplemental Digital Content is Available in the Text., Background: Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence. Methods: The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced. Results: The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence. Conclusions: Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.

Rheumatoid arthritis (RA) is one of the most common inflammatory conditions in the United States affecting approximately 1 million adults. This article briefly reviews the evidence-based diagnosis of RA, mainstays of treatment to prevent joint destruction, and pain management.

Adult asthma is a prevalent chronic medical condition that is associated with high morbidity, mortality, and cost. Early identification, evidence-based diagnosis, and step-wise management can lead to improvements in patient outcomes, decrease exacerbations, and eliminate respiratory function decline as the patient ages.

This article discusses the physiology of normal hearing, the pathophysiology and differential diagnoses of sudden sensorineural hearing loss, and an approach for definitive diagnosis and treatment. A focus is placed on idiopathic sudden sensorineural hearing loss in the adult population in a primary care setting.

Dissection provides a unique opportunity to integrate anatomical and clinical education. Commonly, cadavers are randomly assigned to courses, which may result in skewed representation of patient populations. The primary aim of this study was to determine if the anatomical donors studied by students at the University of Massachusetts Medical School (UMMS) accurately represent the disease burden of the local patient population. This cross-sectional study compared the University of Massachusetts Memorial Medical Center patient claims data and body donation data from the UMMS Anatomical Gift Program (AGP). This study examined age, race, sex, and morbidities within a 10-year timeframe in 401,258 patients and 859 anatomical donors who met inclusion criteria. An independent t test was conducted to compare the mean ages of the two populations. Chi square analysis was conducted on race, sex, and 10 morbidity categories. A Fischer's exact test was conducted for two morbidity categories with n 10. Demographic analysis showed a significant difference in age, and racial representation between the populations. No statistical difference was found regarding sex. Morbidities were separated into 22 ICD-10 categories. Twelve categories were excluded and 10 were analyzed for population comparison. Two categories were over represented and seven were under-represented in the AGP population. One category showed no significant difference between populations. Targeted selection of cadavers in anatomy courses would improve morbidity variability in the anatomy lab. In addition, AGP acceptance guidelines should be evaluated to increase disease variation among the donor population. Clin. Anat. 31:250-258, 2018. © 2017 Wiley Periodicals, Inc.

Background: The development of a comprehensive and structured clinical curriculum map can outline the specific content covered throughout a nurse practitioner program and provide a method for identifying redundancy and omissions in the didactic clinical content. Method: A curriculum map outlining the specific clinical content covered in each didactic course in a Master of Science in Nursing and Doctor of Nursing Practice advanced practice program was created. The curriculum map incorporated accreditation standards, certification testing domains, and common primary care diagnoses. Results: A curriculum map supported the development of organized, consistent, and transparent clinical didactic content across courses and the program. The curriculum map allows for frequent curriculum and course review and updates to help meet program and accreditation standards. Conclusion: The development and implementation of the clinical didactic curriculum map facilitates the integration of core clinical content in an organized manner that builds learning and prepares future nurse practitioners. [ J Nurs Educ. 2018;57(7):440–445.]

The Gulf Coast tick, Amblyomma maculatum Koch, has become increasingly important in public health for its role as a vector of the recently recognized human pathogen, Rickettsia parkeri. More recently, these ticks were also found to harbor a novel spotted fever group rickettsia, "Candidatus Rickettsia andeanae." First identified in Peru, and subsequently reported in ticks collected in the United States, Chile, and Argentina, "Ca. R. andeanae" remains largely uncharacterized, in part because of the lack of a stable isolate. Although the isolation of "Ca. R. andeanae" was recently described in DH82, Vero, and Drosophila S2 cells, its stability in these cell lines was not shown. To evaluate "Ca. R. andeanae" transmission and pathogenicity in vertebrates, as well as further describe biological characteristics of this candidate species to fulfill criteria for its establishment as a new species, availability of a stable isolate is essential. Here we describe the propagation of "Ca. R. andeanae" by using a primary culture derived from naturally infected A. maculatum embryos. Subsequent passage of the "Ca. R. andeanae" isolate to ISE6 (Ixodes scapularis embryonic) and Vero (African green monkey kidney epithelial) cell lines demonstrated limited propagation of the rickettsiae. Treatment of the infected primary cells with tetracycline resulted in cultures negative for "Ca. R. andeanae" by polymerase chain reaction and microscopy. Establishment of an isolate of "Ca. R. andeanae" will promote further investigation into the significance of this tick-associated rickettsia, including its role in spotted fever and interactions with the sympatric species, R. parkeri in A.

Purpose Despite following standard treatment, Pseudomonas keratitis can continue to progress and result in loss of vision or of the eye. Our cases demonstrate that the Morgan Lens can be an effective topical antibiotic delivery vehicle in advanced keratitis. Methods Two patients (3 eyes) with Pseudomonas keratitis were included in this report after failing to respond to intense inpatient topical treatment. Because loss of the eyes was imminent, the Morgan Lenses were used for continuous lavage with ceftazidime (50 mg/mL), in conjunction with other conventional treatment. Results Three days after lavage, corneal cultures became negative in all eyes. Infusion was continued for at least a week to ensure sterilization of the infection before switching to standard topical therapy. The infection in both cases was promptly eradicated and the eyes were rescued. Conclusions The Morgan Lens can be a viable alternative in treating severe and aggressive infectious keratitis or sclerokeratitis. Application of the Morgan Lens is noninvasive and requires minimal training. Intravenous tubing connectors allow for easy swapping between medications, simultaneous administration of multiple medications, and titration of dosing. Additionally, it is cost-effective as the low demand for nursing care essentially eliminates the need for intensive care unit admission.

We examined disparities in prenatal care utilization (PNCU) among U.S. and foreign-born women with chronic conditions. We performed a cross-sectional analyses using data from 2011 to 2012 National Center for Health Statistics Natality Files (n = 6,644,577) to examine the association between maternal nativity (U.S. vs. foreign-born), presence of a chronic condition (diabetes or hypertensive disorder) and PNCU. After adjustment for selected maternal characteristics, overall and among those with chronic conditions, foreign-born women reported significantly lower odds of intensive and adequate PNCU and higher odds of intermediate and inadequate PNCU than U.S.-born women. Few differences in report of no care were found by maternal nativity. These findings suggest that foreign-born women may be receiving some form of prenatal care, but adequacy of care is likely to be lower compared to U.S.-born counterparts, even among those with chronic conditions.

An 11-year-old male with hemophilia A and a known high-titer Factor VIII inhibitor was admitted with retroperitoneal hemorrhage. The patient was receiving infusions of recombinant activated Factor VII (rFVIIa) for a recent elbow hemorrhage when retroperitoneal bleeding commenced. Despite increased dosing of rFVIIa and a dose of activated prothrombin complex concentrate (aPCC), he continued to hemorrhage and required several blood transfusions. Factor XIII was administered 1 hour after rFVIIa and the patient demonstrated cessation of bleeding and normalization of clot strength. Factor XIII may act as an adjuvant in effective clot stabilization in patients with hemophilia and inhibitory antibodies. Pediatr Blood Cancer 2013; 60: E23–E25. © 2013 Wiley Periodicals, Inc.

Purpose. Examine the impact of “point of decision” messages on fruit selection in a single dining hall setting. Setting. Competitive undergraduate liberal arts college in the southeastern United States. Intervention. “Point of decision” messages were compiled into a 35-slide multimedia PowerPoint presentation. Messages were displayed on a computer screen at a “point of decision” between the cookie and fruit stations during lunch for a total of 9 days. Measures. Baseline cookie and fruit consumption was measured 9 days prebaseline and 9 days postbaseline. A random sample of students completed surveys 1 week after the intervention. Analysis. t-tests were used to examine differences between prelevels of fruit consumption and levels measured simultaneously during “point of decision” messages. Descriptive statistics were used to examine perceptions of survey items 1 week postintervention. Results. A significant mean difference in daily fruit consumption was found following the slide presentation (df-8, t = − 2.800; p = .023). Average daily fruit consumption at baseline was 408 (SD = 73.43). Postbaseline average daily fruit consumption significantly increased (533; SD = 102). No significant prebaseline and postbaseline cookie differences were found (p = .226). Approximately 71% of women and 68% of men noticed the “point of decision” messages. Nineteen percent of women and 10% of males reported modifying their food selection as a result of viewing the messages. Conclusion. The “point of decision” messaging significantly influenced fruit selection in a single dining hall setting. (Am J Health Promot 2011;25[5]:298-300.)

Objective To determine whether a novel web-based learning module could adequately prepare first-year undergraduate medical students to skilfully perform their first female pelvic examination. Methods First-year Queen's University medical students without prior training or experience in female pelvic examination were recruited for this study. After viewing key segments of the learning module, students were evaluated while performing a pelvic examination on a female volunteer using a standardized assessment checklist (total score=30 points). Descriptive and comparative statistics were generated. Results Forty-five students participated with a mean age of 24 years (range 20 to 40). The mean score (±SD) on the assessment checklist was 23.9 ± 3.6 points, (range 17 to 30). All study participants received a passing grade of ≥ 50% (15/30 points), and 53.3% (24/45) received an honours grade of ≥ 80% (24/30 points). Of the participants, 88.9% (40/45) agreed that they were well prepared for their first female pelvic examination after viewing the training video. Mean scores were similar for male students (23.9, n=22) and female students (23.8, n=23) (P = 0.90, t test). Mean scores were not higher in those who watched key segments of the learning module more than once. Conclusion This learning module viewed immediately prior to a simulated clinic session afforded first-year medical students the necessary knowledge and skills to perform a first female pelvic examination. This was accomplished with as little as one viewing, and could lead to savings in organizational costs and instruction time for medical school curricula.