Five years later, with double the demographic data, naked mole-rat mortality rates continue to defy Gompertzian laws by not increasing with age.

The naked mole-rat (Heterocephalus glaber) is a mouse-sized rodent species, notable for its eusociality and long lifespan. Previously, we reported that demographic aging, i.e., the exponential increase of mortality hazard that accompanies advancing age in mammals and other organisms, does not occur in naked mole-rats (Ruby et al., 2018), a finding that has potential implications for human healthy aging. The demographic data supporting that conclusion had taken over three decades to accumulate, starting with the original rearing of H. glaber in captivity. This finding was controversial since many of the animals in that study were relatively young. In the 5 years following that study, we have doubled our quantity of demographic data. Here, we re-evaluated our prior conclusions in light of these new data and found them to be not only supported but indeed strengthened. We additionally provided insight into the social dynamics of captive H. glaber with data and analyses of body weight and colony size versus mortality. Finally, we provide a phylogenetically proximal comparator in the form of lifespan data from our Damaraland mole-rat (Fukomys damarensis) colony and demographic meta-analysis of those data along with published data from Ansell's mole-rat (Fukomys anselli). We found Fukomys mortality hazard to increase gradually with age, an observation with inferences on the evolution of exceptional lifespan among mole-rats and the ecological factors that may have accompanied that evolution.

'Everywhere I call, there's nothing available': Understanding the alcohol treatment landscape and needs among unstably housed people who use alcohol in Rhode Island.

INTRODUCTION: Alcohol is a leading cause of morbidity and mortality in the United States and people who are unstably housed are disproportionately impacted by adverse alcohol-related health outcomes. Addressing the needs of unstably housed people with high-intensity alcohol use (i.e., heavy episodic use or binge drinking), including those whose goal is not abstinence, is critical to reducing harms among this population. This study explores the alcohol-related treatment and support needs among unstably housed people who use alcohol. METHODS: Data collection included participant observation and semi-structured interviews (n = 25) with unstably housed people with high-intensity alcohol use. Data were analysed thematically, with attention to structural vulnerability and social-structural forces at shaping perceptions of and experiences with alcohol treatment. RESULTS: Participants underscored how housing instability was critical in precipitating and maintaining heavy alcohol use, with alcohol often used to manage the stress and anxiety related to housing instability. While participants regularly engaged with alcohol treatment programs, program design and barriers to access undermined the effectiveness of these services for participants. Participants described the need for a range of program and service options across a continuum of care to be implemented to support participants in meeting their diverse needs and identified goals regarding alcohol use. DISCUSSION AND CONCLUSIONS: Alcohol treatment and supports need to be modified so that they include a range of harm reduction and abstinence-based models to better meet people's diverse needs. Furthermore, treatment must be paired with permanent and affordable housing to address underlying drivers of alcohol-related harm for unstably housed people.

Evolution of T cells in the cancer-resistant naked mole-rat.

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.

Applications of machine learning in phylogenetics.

Machine learning has increasingly been applied to a wide range of questions in phylogenetic inference. Supervised machine learning approaches that rely on simulated training data have been used to infer tree topologies and branch lengths, to select substitution models, and to perform downstream inferences of introgression and diversification. Here, we review how researchers have used several promising machine learning approaches to make phylogenetic inferences. Despite the promise of these methods, several barriers prevent supervised machine learning from reaching its full potential in phylogenetics. We discuss these barriers and potential paths forward. In the future, we expect that the application of careful network designs and data encodings will allow supervised machine learning to accommodate the complex processes that continue to confound traditional phylogenetic methods.

Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: The VaLiDate-R study.

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.

Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring's health phenotypes in a mouse model.

Mounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male, but not female, offspring developing severe glucose intolerance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated.

Exploring Working Memory Capacity and Efficiency Processes to Understand Working Memory Training Outcomes in Primary School Children.

Despite the abundance of research evaluating working memory training outcomes in children, few studies have examined the underlying cognitive mechanisms. This study aimed to contribute understanding by exploring whether working memory capacity (maximum span) and/or efficiency (basic and cognitive processing speeds), two proposed cognitive mechanisms, are associated with children's working memory performance immediately and 6-months post-intervention. We used data from a previous trial in primary school children (7-11 years) who completed working memory training (n = 52) or an active control (n = 36), comprising 10 sessions (each 20-minutes) in class over two weeks. Children completed five working memory measures at baseline, immediately and 6-months post-intervention: two Backwards Span and two Following Instructions measures (same paradigms as training activities), and one n-back measure (different paradigm). Maximum span, basic and cognitive processing speeds, and performance were calculated for each measure. Associations between change in maximum span, processing speeds and change in performance on the working memory measures from baseline to immediately and 6-months post-intervention did not differ between groups (all p < .05). Maximum span, processing speeds and performance on working memory measures did not differ between groups. Findings provide little evidence that the studied capacity or efficiency processes contribute to understanding working memory training outcomes in primary school children. Furthermore, working memory training did not have benefits for children's working capacity, efficiency or performance up to 6-months post-intervention. It is of interest for future studies to explore cognitive mechanisms, including strategy use, maximum span and information processing, in datasets where training effects are observed.

The Brain Image Library: A Community-Contributed Microscopy Resource for Neuroscientists.

Advancements in microscopy techniques and computing technologies have enabled researchers to digitally reconstruct brains at micron scale. As a result, community efforts like the BRAIN Initiative Cell Census Network (BICCN) have generated thousands of whole-brain imaging datasets to trace neuronal circuitry and comprehensively map cell types. This data holds valuable information that extends beyond initial analyses, opening avenues for variation studies and robust classification of cell types in specific brain regions. However, the size and heterogeneity of these imaging data have historically made storage, sharing, and analysis difficult for individual investigators and impractical on a broad community scale. Here, we introduce the Brain Image Library (BIL), a public resource serving the neuroscience community that provides a persistent centralized repository for brain microscopy data. BIL currently holds thousands of brain datasets and provides an integrated analysis ecosystem, allowing for exploration, visualization, and data access without the need to download, thus encouraging scientific discovery and data reuse.

Implementation of In-Hospital Postpartum Glucose Tolerance Testing for People with Gestational Diabetes.

OBJECTIVE: We aimed to evaluate uptake of the glucose tolerance test performed during delivery hospitalization as part of routine clinical care. STUDY DESIGN: This is a retrospective cohort study of people with GDM at a tertiary center. We collected 9 months of postimplementation data after the in-hospital ("early") glucose tolerance test was adopted as a routine screening option. Adherence was compared between those who elected early glucose tolerance testing versus those who deferred testing to the standard postpartum period. Bivariable statistics including demographics, care team, and postpartum testing/visit attendance were compared between those who received early testing and those who did not using chi-square, Fisher's exact, and t-tests. RESULTS: A total of 681 patients with GDM delivered during the study period. Of those who had an early glucose tolerance test ordered (n = 408), 340 (83.3%) completed the test. Among those who did not complete an early glucose tolerance test (ordered and not completed or never ordered), only 104/341 (30.5%) completed any postpartum glucose testing in the first 12 months of postpartum. There were significant differences in characteristics in terms of race/ethnicity, insurance, type of gestational diabetes (A1GDM vs. A2GDM), diabetes medications, obstetric care provider, and delivery mode. Among those who completed early testing, 43.7% of participants had impaired glucose metabolism and 6.5% had values concerning for overt diabetes mellitus. Among those who deferred testing to the standard 6- to 12-week period, 24.0% had impaired glucose metabolism and none had overt diabetes. Those who completed an early glucose tolerance test had a lower rate of postpartum visit attendance compared with those who deferred (75.6 vs. 91.5%, p < 0.01). CONCLUSION: In this cohort, when the early glucose tolerance test is offered in clinical practice, adherence rates are higher than when the test is deferred until the postpartum visit. KEY POINTS: · Adherence rates with the early glucose tolerance test (GTT) are higher than if the testing is deferred.. · Those who completed an early GTT had a lower rate of postpartum visit attendance compared with those who deferred.. · Offering an in-hospital postpartum GTT can help address low rates of glucose testing postpartum..

Renally Dosed Cefepime Leading to Cefepime-Induced Neurotoxicity: A Case Report.

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Cefepime is most commonly used for urinary tract infections, soft tissue infections, and febrile neutropenia. Up to 15% of ICU patients on cefepime may experience cefepime-induced neurotoxicity (CIN), with risk factors including renal dysfunction, excessive dosage, elevated serum cefepime concentrations, and history of prior brain injury. The adverse effects of CIN, including encephalopathy, seizures, and coma can be resolved with drug cessation, antiepileptics, or hemodialysis. Here, we present the case of CIN in a 59-year-old female patient with long-term cefepime antibiotic prescription for Pseudomonas bacteremia and endocarditis with multiple risk factors for reduced renal function. We discuss the relevant risk factors and preventive measures that may have prevented her from developing CIN, as well as the importance of early recognition and prevention of CIN in patient care.

Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

OBJECTIVES: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). METHODS: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. RESULTS: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. CONCLUSIONS: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Epidural analgesia and post-operative ileus after incisional hernia repair with transversus abdominis release: Results of a 5-year quality improvement initiative.

INTRODUCTION: The optimal pain management strategy after open ventral hernia repair (VHR) with transversus abdominus release (TAR) is unknown. Opioids are known to have an inhibitory effect on the GI tract and cause postoperative ileus. Epidural analgesia is associated with lower postoperative ileus rates but may contribute to other postoperative complications. A propensity-matched retrospective review published by our group in 2018 found that epidural analgesia was associated with an increased length of stay and any postoperative complication after VHR. Epidural analgesia was therefore abandoned by our group following this publication. We aimed to determine if discontinuation of epidural analgesia affected ileus rates after open VHR. METHODS: Patients who underwent open VHR with TAR from August 2014 to January 2022 â€‹at Cleveland Clinic Foundation with at least 30-day follow-up were retrospectively identified using the Abdominal Core Health Quality Collaborative registry. Patients with and without epidural analgesia were compared. The primary outcome was post-operative ileus. Additional outcomes included length of stay, deep venous thrombosis (DVT), pneumonia, wound complications and pain requiring intervention. RESULTS: A total of 2570 patients were included: 420 had an epidural, 2150 did not. Preoperative patient and hernia characteristics were similar between both groups. Mean hernia width was 15.5 â€‹cm in the epidural group and 16.1 â€‹cm in the no epidural group. In the epidural group, ileus was seen in 9 of 420 (2.15%) of patients which was significantly less than in the no epidural group, 400 of 2150 (18.6%), p=>0.001. On multivariate analysis, epidurals were predictive of lower risk of ileus (OR 0.04, 95%CI 0.01-0.17, p â€‹= â€‹0.001) and pain requiring intervention (OR 0.02, 95%CI 0.00-0.71, p â€‹= â€‹0.02). Epidural analgesia was not associated with increased DVT rates, pneumonia, length of stay, SSI, or SSOPI. DISCUSSION: Discontinuation of epidural analgesia was associated with a 9-fold increase in ileus rates after VHR with TAR. Epidurals may play an important role in limiting postoperative opioid use and therefore reducing risk of ileus. Other postoperative complications including pneumonia and venous thrombosis were not impacted by epidurals. Further prospective studies are needed to further define a ventral hernia patient population who will benefit from epidural analgesia.

Participation in the national cervical screening programme among women from New South Wales, Australia, by place of birth and time since immigration: A data linkage analysis using the 45 and up study.

OBJECTIVE: Equitable elimination of cervical cancer in Australia within the next decade will require high National Cervical Screening Program (NCSP) participation by all subgroups of women. The aim of this study was to examine the participation of immigrants compared to Australian-born women. METHODS: Participation in the NCSP (≥1cytology test) over a 3-year (2010-2012) and 5-year (2008-2012) period, by place of birth and time since immigration was examined using individually linked data of 67,350 New South Wales (NSW) women aged ≥45 enrolled in the 45 and Up Study. RESULTS: Three-year cervical screening participation was 77.0% overall. Compared to Australian-born women (77.8%), 3-year participation was lower for women born in New Zealand (adjusted odds ratio 0.77, 95% confidence interval 0.69-0.87), Oceania (0.67, 0.51-0.89), Middle East/North Africa (0.76, 0.60-0.97), South-East Asia (0.72, 0.60-0.87), Chinese Asia (0.82, 0.69-0.97), Japan/South Korea (0.68, 0.50-0.94), and Southern/Central Asia (0.54, 0.43-0.67), but higher for women from Malta (2.85, 1.77-4.58) and South America (1.33, 1.01-1.75). Non-English-speaking-at-home women were less likely to be screened than English-speaking-at-home women (0.85, 0.78-0.93). Participation increased with years lived in Australia but remained lower in immigrant groups compared to Australian-born women, even after ≥20 years living in Australia. Similar results were observed for 5-year participation. CONCLUSIONS: Women born in New Zealand, Oceania, and parts of Asia and the Middle East had lower NCSP participation, which persisted for ≥20 years post-immigration. The NCSP transition to primary HPV screening, and the introduction of the universal self-collection option in 2022, will offer new opportunities for increasing screening participation for these groups.

Tipping the scale in abdominal wall reconstruction: An analysis of short- and long-term outcomes by body mass index.

BACKGROUND: Morbid obesity, with a body mass index 35 kg/m2, is a commonly used cutoff for denying elective transversus abdominis release. Although obesity is linked to short-term wound morbidity, its effect on long-term outcomes remains unknown, calling into question if a cutoff is justified. We sought to compare 1-year recurrence rates after transversus abdominis release based on body mass index and to evaluate short- and long-term outcomes. METHODS: Patients undergoing open, clean transversus abdominis release from August 2014 to January 2022 at our institution with 1-year follow-up completed were identified. Univariate and multivariable analyses were performed to determine the association of body mass index with 90-day wound events, 1-year hernia recurrence, and hernia-specific quality of life. Covariates included body mass index, diabetes, recurrent hernia, hernia width, fascial closure, surgical site occurrence requiring procedural intervention, previous abdominal wall surgical site infection, inflammatory bowel disease, mesh weight, and mesh-to-hernia size ratio. RESULTS: A total of 1,089 patients were included. Increasing body mass index was associated with surgical site infection (adjusted odds ratio = 1.59; 95% confidence interval, 1.14-1.77; P < .01) and surgical site occurrence (adjusted odds ratio = 1.42; 95% confidence interval, 1.13-1.74; P < .01) but was not associated with surgical site occurrence requiring procedural intervention. Hernia width was associated with surgical site occurrence (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P < .01) and surgical site occurrence requiring procedural intervention (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P = .01). Hernia recurrence rate at 1 year was lower for the body mass index ≥35 kg/m2 group (7% vs 12%; P = .02). Hernia width (odds ratio = 1.33; 95% confidence interval, 1.02-1.74; P = .04) was associated with recurrence; body mass index was not (P = .11). Both groups experienced significant improvement in hernia-specific quality of life at 1 year. CONCLUSION: Morbid obesity is associated with 90-day wound morbidity; however, short-term complications did not translate to higher reoperation or long-term recurrence rates. The impact of body mass index on hernia recurrence is likely overstated. An arbitrary body mass index cutoff of 35 kg/m2 should not be used to deny symptomatic patients abdominal wall reconstruction.

The use of Lentilactobacillus buchneri PJB1 and Lactiplantibacillus plantarum MTD1 on the ensiling of whole-plant corn silage, snaplage, and high-moisture corn.

Experiments were conducted over a 3-yr period to evaluate the effects of bacterial inoculants on the fermentation profile and aerobic stability of whole-plant corn silage (WPC), snaplage (SNA), and high-moisture corn (HMC). Whole-plant corn was inoculated with Lentilactobacillus buchneri PJB1 in combination with Lactiplantibacillus plantarum MTD1 or with Lpb. plantarum alone (experiments 1 and 2). Snaplage (experiment 3) and HMC (experiments 4 and 5) were inoculated with Len. buchneri in combination with Lpb. plantarum or with Len. buchneri alone. After inoculation, the feedstuffs were ensiled in 7.57-L silos and stored at 21 ± 2°C for 30 or 90 d. In experiment 5, silage was subjected to air stress for 2 h every 2 wk through 42 d and then for 2 h/wk until 90 d and had samples analyzed for their bacterial community composition by metagenomics. Overall, in all experiments, silages inoculated with Len. buchneri alone or in combination with Lpb. plantarum had more acetic acid and 1,2-propanediol and fewer yeasts than uninoculated silages. After 30 d of ensiling, inoculation with Len. buchneri alone or in combination with Lpb. plantarum did not affect the aerobic stability of SNA, but it slightly increased the stability of WPC and markedly improved the stability of HMC. After 90 d of ensiling, inoculation with Len. buchneri alone or in combination with Lpb. plantarum markedly improved the aerobic stability of WPC, SNA, and HMC. In experiment 5, inoculation increased the relative abundance (RA) of Lactobacillaceae and reduced the RA of Enterobacteriaceae and Leuconostocaceae in HMC at 30 and 90 d and the RA of Clostridiaceae in non-air-stressed HMC at 90 d. Air-stressed HMC inoculated with Len. buchneri had less lactic acid, more acetic acid and 1,2-propanediol, and markedly greater aerobic stability than uninoculated air-stressed HMC at 90 d. In conclusion, inoculation with Len. buchneri PJB1 alone or in combination with Lpb. plantarum MTD1 increased the production of acetic acid and 1,2-propanediol, inhibited yeasts development, and improved the aerobic stability of WPC, SNA, and HMC. In HMC, inoculation markedly improved aerobic stability as soon as after 30 d of ensiling, and after 90 d, inoculation improved stability even under air stress conditions.

Revisiting femoral hernia diagnosis rates by patient sex in inguinal hernia repairs.

INTRODUCTION: Guidelines recommend MIS repairs for females with inguinal hernias, despite limited evidence. We investigated rates of femoral hernias intraoperatively noted during MIS and Lichtenstein repairs in females. METHODS: ACHQC was queried for adult females undergoing inguinal hernia repair between January 2014-November 2022. Outcomes included identified femoral hernia and size, hernia recurrence, quality of life, and sex-based recurrence. RESULTS: 1357 and 316 females underwent MIS and Lichtenstein inguinal repair respectively. Femoral hernias were identified more frequently in MIS than open repairs (27%vs12%; (p â€‹< â€‹0.001). Most femoral hernias in MIS (61%) and Lichtenstein repairs (62%) were <1.5 â€‹cm(p â€‹< â€‹0.001). Identification rates of femoral hernias >3 â€‹cm were 1% overall(p â€‹= â€‹0.09). Surgeon and patient-reported recurrences were similar between approaches at 1-5-years for females(p â€‹> â€‹0.05 for all) and similar between sexes(p â€‹> â€‹0.05). CONCLUSION: Most incidental femoral hernias are small and both repair approaches demonstrated similar outcomes. The recommendation for MIS inguinal hernia repairs in females is potentially overstated.

Molecular pathways in placental-fetal development and disruption.

The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D. Some of these are well-established as biomarkers of placental-fetal endocrine disruption, while others are not well studied and were selected based on discovery analyses of the placental transcriptome. A literature search on these biomarkers summarizes evidence of placenta-specific production and regulation of each biomarker, and their role in fetal reproductive tract, brain, and other specific domains of fetal development. In this review, we extend the theory of fetal programming to placental-fetal programming.

Guillain-Barré Syndrome Presenting as Symmetrical Proximal Muscle Weakness: An Atypical Presentation.

Guillain-Barré syndrome occurs via molecular mimicry when a trigger sets off an immune response on peripheral nerve epitopes. Patients typically report an antecedent infection, such as an upper respiratory infection or Campylobacter jejuni gastroenteritis. It is typically characterized by progressive, symmetric muscle weakness with absent/decreased deep tendon reflexes. Most cases in the literature report that the paralysis begins in the legs distally and ascends to the extremities. Patients may have sensory symptoms or dysautonomia as well. Notable variant forms include acute motor axonal neuropathy, acute motor/sensory neuropathy, Miller Fisher syndrome, and Bickerstaff brainstem encephalitis. Diagnosis is confirmed if a lumbar puncture shows albuminocytologic dissociation (typically 45 to 200 mg/dL). Nerve conduction studies may also be considered but are not necessary. Management is largely supportive, but intravenous immunoglobulin and/or plasmapheresis for more severe cases may be considered.

Addressing COVID-19 vaccine hesitancy in rural community pharmacies: a protocol for a stepped wedge randomized clinical trial.

BACKGROUND: Uptake of COVID-19 vaccines remains problematically low in the USA, especially in rural areas. COVID-19 vaccine hesitancy is associated with lower uptake, which translates to higher susceptibility to SARS-CoV-2 variants in communities where vaccination coverage is low. Because community pharmacists are among the most accessible and trusted health professionals in rural areas, this randomized clinical trial will examine implementation strategies to support rural pharmacists in delivering an adapted evidence-based intervention to reduce COVID-19 vaccine hesitancy. METHODS: We will use an incomplete stepped wedge trial design in which we will randomize 30 rural pharmacies (unit of analysis) to determine the effectiveness and incremental cost-effectiveness of a standard implementation approach (consisting of online training that describes the vaccine hesitancy intervention, live webinar, and resource website) compared to adding on a virtual facilitation approach (provided by a trained facilitator in support of the delivery of the vaccine hesitancy counseling intervention by pharmacists). The intervention (ASORT) has been adapted from an evidence-based vaccine communication intervention for HPV vaccines through a partnership with rural pharmacies in a practice-based research network in seven southern US states. ASORT teaches pharmacists how to identify persons eligible for COVID-19 vaccination (including a booster), solicit and address vaccine concerns in a non-confrontational way, recommend the vaccine, and repeat the steps later if needed. The primary trial outcome is fidelity to the ASORT intervention, which will be determined through ratings of recordings of pharmacists delivering the intervention. The secondary outcome is the effectiveness of the intervention, determined by rates of patients who agree to be vaccinated after receiving the intervention. Other secondary outcomes include feasibility, acceptability, adoption, reach, and cost. Cost-effectiveness and budget impact analyses will be conducted to maximize the potential for future dissemination and sustainability. Mixed methods will provide triangulation, expansion, and explanation of quantitative findings. DISCUSSION: This trial contributes to a growing evidence base on vaccine hesitancy interventions and virtual-only facilitation of evidenced-based practices in community health settings. The trial will provide the first estimate of the relative value of different implementation strategies in pharmacy settings. TRIAL REGISTRATION: NCT05926544 (clinicaltrials.gov); 07/03/2023.