Exploring the Experiential Journey of Women with PCOS Across the Lifespan: A Qualitative Inquiry.

Introduction: Peri-postmenopausal women with the chronic condition polycystic ovary syndrome (PCOS) remain at cardiometabolic risk and/or subsist with established comorbidity while continuing to manage persistent PCOS signs and symptoms, such as hirsutism. Thus, PCOS transcends the reproductive years, yet there is sparse scientific literature on the peri-postmenopausal years of women with PCOS. Purpose: To explore how peri-postmenopausal women's perceptions about PCOS have changed over the lifespan since their PCOS diagnosis. Methods: A cross-sectional survey with one qualitative question was conducted via Research Electronic Data Capture (REDCap) among women with PCOS aged ≥43 years, who were all recruited from PCOS-specific Facebook pages. Of the 107 women completing the survey, 72 substantively answered the qualitative question. The qualitative responses were analyzed using the steps of reflexive thematic analysis. Themes were interpreted and discussed through the lens of the bioecological conceptual model. Results: Respondents were 47.6 (±4.1) years of age, primarily White (87.5%), employed full time (65.3%), and married (75%) with children (68%). Four overall themes were identified: 1) dismissal 2) information desert, 3) PCOS experience over the lifespan, and 4) mindset. Conclusion: The study findings illustrated the unique healthcare needs among peri-postmenopausal women with PCOS. Further research is needed to further explore their healthcare concerns and psychosocial needs followed by studies that develop and assess interventions that promote symptom and adaptive coping strategies across their lifespan.

US Military Veteran Perspectives on Eating Disorder Screening, Diagnosis, and Treatment: A Qualitative Study.

OBJECTIVE: We aimed to explore US veteran perspectives on eating disorder screening, diagnosis, patient-provider conversations, and care in the Veterans Health Administration (VHA). METHOD: Rapid qualitative analysis of 30-45 min phone interviews with 16 (N = 16) veterans with an electronic health record ICD-10 eating disorder diagnosis, who received care at one of two VHA healthcare systems in Connecticut or California. Topics covered included: conversations with providers about eating disorder symptoms, diagnosis, and referral to treatment; feedback about an eating disorder screener, and; reflections on eating disorders among veterans and VHA's effort to address them. RESULTS: Most veterans reported difficulty understanding and defining the problems they were experiencing and self-diagnosed their eating disorder before discussing it with a provider. Treatment referrals were almost universally for being overweight rather than for an eating disorder, often leading veterans to feel misunderstood or marginalized. Overall, veterans were enthusiastic about the screener, preferred screening to be conducted by primary care providers, and noted that conversations needed to be non-stigmatizing. There was consensus that VHA is not doing enough to address this issue, that group support and therapy could be beneficial, and that resources needed to be centralized and accessible. DISCUSSION: For the most part, veterans felt that, at best, eating disorders and disordered eating are overlooked, and at worst, conflated with overweight. The majority of veterans got referred for weight loss or weight management services but would welcome the opportunity to be screened for, and referred to, eating disorder treatment.

Palladium-Catalyzed Addition of Aryl Halides to N-Sulfinylamines for the Synthesis of Sulfinamides.

Sulfinamides are versatile, synthetically useful intermediates, and final motifs. Traditional methods to synthesize sulfinamides generally require substrates with preinstalled sulfur centers. However, these precursors have limited commercial availability, and the associated synthetic routes often require harsh reaction conditions and highly reactive reagents, thus severely limiting their application. Herein, we report the synthesis of sulfinamides from aryl and alkenyl (pseudo)halides and N-sulfinylamines, enabled by palladium catalysis. The reactions use mild conditions and are achieved without the use of highly reactive preformed organometallic reagents, resulting in transformations of broad generality and high functional group tolerance. In particular, substrates featuring protic and electrophilic functional groups can be used successfully. The modification of complex aryl cores and natural product derivatives demonstrates the utility of this method.

What is the Vagal-Adrenal Axis?

Some recent publications have used the term "vagal-adrenal axis" to account for mechanisms involved in the regulation of inflammation by electroacupuncture. This concept proposes that efferent parasympathetic nerve fibers in the vagus directly innervate the adrenal glands to influence catecholamine secretion. Here, we discuss evidence for anatomical and functional links between the vagi and adrenal glands that may be relevant in the context of inflammation and its neural control by factors, including acupuncture. First, we find that evidence for any direct vagal parasympathetic efferent innervation of the adrenal glands is weak and likely artifactual. Second, we find good evidence that vagal afferent fibers directly innervate the adrenal gland, although their function is uncertain. Third, we highlight a wealth of evidence for indirect pathways, whereby vagal afferent signals act via the central nervous system to modify adrenal-dependent anti-inflammatory responses. Vagal afferents, not efferents, are thus the likely key to these phenomena.

Total ankle arthroplasty improves discrete and continuous stance phase gait symmetry.

BACKGROUND: Total ankle arthroplasty (TAA) is used to treat symptomatic end-stage ankle arthritis (AA). However, little is known about TAA's effects on gait symmetry. RESEARCH QUESTION: Determine if symmetry changes from before surgery through two years following TAA utilizing the normalized symmetry index (NSI) and statistical parametric mapping (SPM). METHODS: 141 patients with end-stage unilateral AA were evaluated from a previously collected prospective database, where each participant was tested within two weeks of surgery (Pre-Op), one year and two years following TAA. Walking speed, hip extension angle and moment, hip flexion angle, ankle plantarflexion angle and moment, ankle dorsiflexion angle, weight acceptance (GRF1), and propulsive (GRF2) vertical ground reaction forces were calculated for each limb. Gait symmetry was assessed using the NSI. A linear mixed effects model with a single response for each gait symmetry variable was used to examine the fixed effect of follow-up time (Pre-Op, Post-1 yr, Post-2 yr) and the random effect of participant with gait speed as a covariate in the model. A one-dimensional repeated measures analysis of variance (ANOVA) statistical parameter mapping (SPM) was completed to examine differences in the time-series NSI to determine regions of significant differences between follow-up times. RESULTS: Relative to Pre-Op values, GRF1, and GRF2 showed increased symmetry for discrete metrics and the time-series NSI across sessions. Hip extension moment had the largest symmetry improvement. Ankle plantarflexion angle was different between Pre-Op and Post-2 yr (p=0.010); and plantarflexion moment was different between Pre- Op and each post-operative session (p<0.001). The time-series Ankle Angle NSI was greater during the early stance phase in the Pre-Op session compared to Post-2 yr. SIGNIFICANCE: Symmetry across most of the stance phase improved following TAA indicating that TAA successfully improves gait symmetry and future work should determine if these improvements restore symmetry to levels equivalent with health age-match controls.

"We rely on each other": A qualitative exploration of rural Eastern Region Native American experiences during the COVID-19 pandemic.

Background: Native American communities suffered disproportionately negative effects during the COVID-19 pandemic, yet no research has explored the experiences of rural Eastern Region Native Americans. Methods: Informed by the Native Reliance Model and Indigenous Standpoint Theory, we conducted a qualitative descriptive project in the Spring and Summer of 2022; data included semi-structured interviews and focus groups with 24 individuals representing five South Carolina tribal groups. Findings: Thematic analysis yielded four emergent themes: 1) "Let's just finish the Indians off": Pandemic distrust rooted in historical and contemporary Native American experiences; 2) "We have been misled": Making sense of conflicting public health information; 3) "I'm not giving it to some innocent person": COVID-19 mitigation behaviors as Native American cultural practice; and 4) "We put the plan in place": Self-advocacy and action as a source of Native American pride and responsibility. Interpretation: These participants demonstrated resiliency grounded in family and tribal ties, even in the face of personal losses, economic struggles, and healthcare barriers. To strike a balance between cultural traditions and public health recommendations, public health practitioners should 1) build partnerships with community leaders, elders, and tribal health authorities to facilitate the development of culturally respectful interventions that address specific health concerns in the context of historical traumas; and 2) implement alternative methods of communication and engagement to ensure equitable access to healthcare services in rural locations, such as collaborating with community organizations, deploying mobile health units, and utilizing traditional channels of communication within these communities.

The Use of Musculoskeletal Fitness Measures as Indicators of Performance in Police Occupational Tasks.

Fitness testing is employed by some law enforcement agencies to assure performance in occupational tasks. The aim of this study was to investigate associations between musculoskeletal fitness assessment scores and performance in police occupational tasks. Retrospective data from 106 law enforcement officers who completed five musculoskeletal fitness assessments (vertical jump (VJ), hand grip strength, leg back dynamometer, 1-minute push-ups and sit-ups) and three routine occupational tasks (1.22m fence jump (FJ), 8.5m victim drag (VD) with 101kg and a get-up (GU)) were collected. A standard multiple regression was performed to determine if the results in fitness assessments were predictive of performance in the occupational tasks. Models combining all fitness assessments significantly predicted performance in FJ (F(5,88)=12.228, p<0.001; adjusted R2=0.38), VD (F(5,88)=9.407, p<0.001; adjusted R2=0.31) and GU (F(5,87)=14.319, p<0.001; adjusted R2=0.42). Further analysis of individual predictors highlighted that performance in the VJ test was a significant contributor for all models, uniquely predicting 15% of FJ (p<0.001), 4% of VD (p=0.03) and 8% of GU (p=0.001) performance. Grip strength uniquely contributed 3% to performance in the VD (p=0.05) and performance in the sit-up test contributed 8% to GU performance (p=0.001). Performance in police-specific occupational tasks requires a combination of muscular strength, power, and endurance. These musculoskeletal fitness components should be ideally assessed in recruitment and return-to work practices to ensure officers can safely and optimally perform their occupational requirements.

Bedaquiline: what might the future hold?

Tuberculosis drug development has stagnated for decades, so the recent availability of bedaquiline is welcome. Bedaquiline-containing regimens, now the first-line therapy recommended by WHO, have transformed the treatment of drug-resistant tuberculosis, offering safer and more effective oral treatment options. However, key obstacles need to be overcome to ensure global access and prevent the rapid development of resistance against this promising class of drugs. In this Personal View, building on an international workshop held in 2023, we evaluate the current evidence and suggest possible ways forward, recognising the tension between increasing use and slowing the rise of resistance. We also discuss problems in accessing bedaquiline-containing regimens, the potential widening of their use beyond drug-resistant tuberculosis, and lessons for utilising new drugs as they are developed.

Lateral Corpectomy for Tumor at L1: A Surgical Technique: 2-Dimensional Operative Video.

The thoracolumbar junction is a complex and challenging anatomical region due to its heterogeneous array of planes and structures.1 Navigating this region during a lateral approach to the spine is a challenge that requires a thorough understanding of the anatomy. We present a case of a 54-year-old woman with a 7-year history of breast cancer who presented with low back pain after running a marathon. To date, the patient had deferred medical management. Imaging revealed Stage IV differentiated invasive ductal carcinoma with extensive bony metastatic disease in multiple areas of the spine. The patient underwent a right-sided minimally invasive retrodiaphragmatic approach to the thoracolumbar junction for L1 corpectomy, placement of an expandable cage, and posterior percutaneous pedicle screw segmental fixation from T11 to L3 with robotic guidance. Patient consent was obtained for the following procedure, and IRB approval was not required for publication of this single patient case report.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility. To test this hypothesis, we produced a knockout mouse model. Axdnd1-/- males were sterile at all ages but presented with an evolving testis phenotype wherein they could undergo one round of histologically replete spermatogenesis followed by a rapid depletion of the seminiferous epithelium. Marker experiments identified a role for AXDND1 in maintaining the balance between differentiation-committed and self-renewing spermatogonial populations, resulting in disproportionate production of differentiating cells in the absence of AXDND1 and increased sperm production during initial spermatogenic waves. Moreover, long-term spermatogonial maintenance in the Axdnd1 knockout was compromised, ultimately leading to catastrophic germ cell loss, destruction of blood-testis barrier integrity and immune cell infiltration. In addition, sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively these data identify AXDND1 as an atypical dynein complex-related protein with a role in protein/vesicle transport of relevance to spermatogonial function and sperm tail formation in mice and humans. This study underscores the importance of studying the consequences of gene loss-of-function on both the establishment and maintenance of male fertility.

Insights into mycobacteriome composition in Mycobacterium bovis-infected African buffalo (Syncerus caffer) tissue samples.

Animal tuberculosis significantly challenges global health, agriculture, and wildlife conservation efforts. Mycobacterial cultures are resource-intensive, time-consuming, and challenged by heterogeneous populations. In this study, we employed a culture-independent approach, using targeted long-read-based next-generation sequencing (tNGS), to investigate the mycobacterial composition in 60 DNA samples extracted from Mycobacterium bovis infected culture-confirmed African buffalo tissue. We detected mycobacterial DNA in 93.3% of the samples and the sensitivity for detecting Mycobacterium tuberculosis complex (MTBC) was 91.7%, demonstrating a high concordance of our culture-independent tNGS approach with mycobacterial culture results. In five samples, we identified heterogenous mycobacterial populations with various non-tuberculous mycobacteria, including members of the Mycobacterium avium complex (MAC), M. smegmatis, and M. komaniense. The latter Mycobacterium species was described in South Africa from bovine nasal swabs and environmental samples from the Hluhluwe-iMfolozi Park, which was the origin of the buffalo samples in the present study. This finding suggests that exposure to environmental mycobacteria may confound detection of MTBC in wildlife. In conclusion, our approach represents a promising alternative to conventional methods for detecting mycobacterial DNA. This high-throughput technique enables rapid differentiation of heterogeneous mycobacterial populations, which will contribute valuable insights into the epidemiology, pathogenesis, and microbial synergy during mycobacterial infections.

The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

BACKGROUND: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics. OBJECTIVES: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB. METHODS: We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates. RESULTS: The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%. CONCLUSION: No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.

Living with low muscle mass and its impact throughout curative treatment for lung cancer: A qualitative study.

OBJECTIVES: To 1) explore the experience of patients with lung cancer with low muscle mass or muscle loss during treatment and the ability to cope with treatment, complete self-care, and 2) their receptiveness and preferences for nutrition and exercise interventions to halt or treat low muscle mass/muscle loss. METHODS: This was a qualitative study using individual semi-structured interviews conducted using purposive sampling in adults with a diagnosis of non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC), treated with curative intent chemo-radiotherapy or radiotherapy. Patients who presented with computed tomography-assessed low muscle mass at treatment commencement or experienced loss of muscle mass throughout treatment were included. Data were analysed using thematic analysis. RESULTS: Eighteen adults (mean age 73 ± SD years, 61% male) with NSCLC (76%) treated with chemo-radiotherapy (76%) were included. Three themes were identified: 1) the effect of cancer and its treatment; 2) engaging in self-management; and 3) impact and influence of extrinsic factors. Although experiences varied, substantial impact on day-to-day functioning, eating, and ability to be physically active was reported. Patients were aware of the overall importance of nutrition and exercise and engaged in self-initiated or health professional supported self-management strategies. Early provision of nutrition and exercise advice, guidance from health professionals, and support from family and friends were valued, albeit with a need for consideration of individual circumstances. CONCLUSION: Adults with NSCLC with or experiencing muscle loss described a diverse range of experiences regarding treatment. The types of support required were highly individual, highlighting the crucial role of personalised assessment of needs and subsequent intervention.

Quality measure for screening for adult obstructive sleep apnea by primary care providers: 2024 update after measure maintenance.

Obstructive sleep apnea (OSA) is a prevalent respiratory sleep disorder that, when left undiagnosed or untreated, can lead to adverse outcomes. There continue to be gaps and variations in screening adults who are high risk for OSA in the primary care setting, leading to many adults in the United States going undiagnosed. As a part of the ongoing AASM quality measure maintenance initiative, the AASM Quality Measures Task Force reviewed the original screening for adult obstructive sleep apnea by primary care physicians quality measure. The measure was updated to further address the adult populations who are at high risk for OSA to ensure that the measure is consistent with the most current medical literature, increasing the likelihood that patients at high risk for OSA are properly screened for the sleep disorder.

Shoulder Taps: Relationships Between a New Movement Screening Assessment with Body Composition and Physical Fitness in Law Enforcement Recruits.

The overhead squat, as part of the Functional Movement Screen (FMS), can analyze total- and lower-body mechanics. Shoulder taps, which incorporates a push-up position and challenges shoulder, trunk, and hip stability, may identify movement deficiencies indicated by multiple FMS actions which could be useful for law enforcement recruits. This study determined overhead squat and shoulder taps relationships, associations between these screens with body composition and fitness, and differences in body composition and fitness according to overhead squat/shoulder taps scores in recruits by sex. Retrospective analysis was conducted on 202 recruit datasets (158 males, 44 females), which included: overhead squat and shoulder taps scores; age, height, and body mass; skeletal muscle (SMM%) and body fat mass (BFM%) percentage; waist-to-hip ratio; grip strength; 60-s push-ups and sit-ups; 75-yard pursuit run; vertical jump; medicine ball throw; and multistage fitness test (MSFT). Spearman's correlations (p<0.05) determined relationships between the overhead squat and shoulder taps, and between the screens and other variables. Kruskall-Wallis H tests compared the variables when recruits were split into groups based on overhead squat/shoulder taps scores. A significant correlation was found between the screens for male (ρ=0.231) but not female (ρ=0.258) recruits. Overhead squat score had a moderate relationship with BFM% in females (ρ=-0.312). Shoulder taps had a small relationship with SMM% in males (ρ=0.163). There were no differences in body composition and fitness when recruits were split based on screen scores (p=0.086-0.994). While morphology may influence movement screen performance, the screens had minimal capacity for associating movement deficiencies to fitness.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

BACKGROUND: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs. METHODS: This prospective, observational study enrolled patients with NSCLC concomitantly using a DOAC and SMI. The primary outcome was the proportion of patients with DOAC plasma trough (Ctrough) and peak (Cpeak) concentrations outside expected ranges. Secondary outcomes included DOAC treatment modifications, incidence of bleeding and thromboembolic events and feasibility evaluation of pharmacokinetically guided DOAC dosing. RESULTS: Thirty-three patients were analysed. Thirty-nine percent (13/33) had DOAC Ctrough and/or Cpeak were outside the expected ranges in 39% (13/33). In 71% (5/7) of patients with DOAC concentrations quantified before and during concurrent SMI use, DOAC Ctrough and/or Cpeak increased or decreased >50% upon SMI initiation. In all patients in whom treatment modifications were deemed necessary, DOAC concentrations were adjusted to within the expected ranges. CONCLUSION: Proactive monitoring showed that a substantial proportion of patients had DOAC concentrations outside the expected ranges. DOAC concentrations were successfully normalised after treatment modifications. These results highlight the importance of proactive monitoring of DOAC-SMI DDIs to improve treatment in patients with NSCLC.

Ablation of the dystrophin Dp71f alternative C-terminal variant increases sarcoma tumour cell aggressiveness.

Alterations in Dp71 expression, the most ubiquitous dystrophin isoform, have been associated with patient survival across tumours. Intriguingly, in certain malignancies, Dp71 acts as a tumour suppressor, while manifesting oncogenic properties in others. This diversity could be explained by the expression of two Dp71 splice variants encoding proteins with distinct C-termini, each with specific properties. Expression of these variants has impeded the exploration of their unique roles. Using CRISPR/Cas9, we ablated the Dp71f variant with the alternative C-terminus in a sarcoma cell line not expressing the canonical C-terminal variant, and conducted molecular (RNAseq) and functional characterisation of the knockout cells. Dp71f ablation induced major transcriptomic alterations, particularly affecting the expression of genes involved in calcium signalling and ECM-receptor interaction pathways. The genome-scale metabolic analysis identified significant downregulation of glucose transport via membrane vesicle reaction (GLCter) and downregulated glycolysis/gluconeogenesis pathway. Functionally, these molecular changes corresponded with, increased calcium responses, cell adhesion, proliferation, survival under serum starvation and chemotherapeutic resistance. Knockout cells showed reduced GLUT1 protein expression, survival without attachment and their migration and invasion in vitro and in vivo were unaltered, despite increased matrix metalloproteinases release. Our findings emphasise the importance of alternative splicing of dystrophin transcripts and underscore the role of the Dp71f variant, which appears to govern distinct cellular processes frequently dysregulated in tumour cells. The loss of this regulatory mechanism promotes sarcoma cell survival and treatment resistance. Thus, Dp71f is a target for future investigations exploring the intricate functions of specific DMD transcripts in physiology and across malignancies.

Fetal bradycardia in open versus fetoscopic prenatal repair of spina bifida.

OBJECTIVE: To compare the occurrence of fetal bradycardia in open versus fetoscopic fetal spina bifida surgery. METHODS: This is a single-institution retrospective cohort study of patients undergoing open (n = 25) or fetoscopic (n = 26) spina bifida repair between 2017 and 2022. From October 2017 to June 2020, spina bifida repairs were performed via an open classical hysterotomy, and from November 2020 to June 2022 fetoscopic repairs were performed following transition to this technique. Fetal heart rate (FHR) in beats per minute (bpm) was recorded via echocardiography every 15 min during the procedure. Cohort characteristics, fetal bradycardia and maternal physiologic parameters were compared between the groups. RESULTS: Fetuses undergoing an open repair more frequently developed bradycardia defined as <110 bpm (32% vs. 3.8%, p = 0.008), and a trend was observed for FHR decreases more than 25 bpm from baseline (20% vs. 3.8%, p = 0.073). Profound bradycardia less than 80 bpm was rare, occurring in only three operations (two in open, one in fetoscopic repair) with two fetuses (one in each group) requiring emergency cesarean delivery. CONCLUSION: When compared to open fetal surgery, fetal bradycardia occurred less frequently in fetoscopic surgery despite a significantly greater anesthetic exposure and the use of the intraamniotic carbon dioxide insufflation.