Disruptions in Sleep Health and Independent Associations with Psychological Distress in Close Family Members of Cardiac Arrest Survivors: A Prospective Study.

Background: While recent guidelines have noted the deleterious effects of poor sleep on cardiovascular health, the upstream impact of cardiac arrest-induced psychological distress on sleep health metrics among families of cardiac arrest survivors remains unknown. Methods: Sleep health of close family members of consecutive cardiac arrest patients admitted at an academic center (8/16/2021 - 6/28/2023) was self-reported on the Pittsburgh Sleep Quality Index (PSQI) scale. The baseline PSQI administered during hospitalization was cued to sleep in the month before cardiac arrest. It was then repeated one month after cardiac arrest, along with the Patient Health Questionnaire-8 (PHQ-8) to assess depression severity. Multivariable linear regressions estimated the associations of one-month total PHQ-8 scores with changes in global PSQI scores between baseline and one month with higher scores indicating deteriorations. A prioritization exercise of potential interventions categorized into family's information and well-being needs to alleviate psychological distress was conducted at one month. Results: In our sample of 102 close family members (mean age 52±15 years, 70% female, 21% Black, 33% Hispanic), mean global PSQI scores showed a significant decline between baseline and one month after cardiac arrest (6.2±3.8 vs. 7.4±4.1; p<0.01). This deterioration was notable for sleep quality, duration, and daytime dysfunction components. Higher PHQ-8 scores were significantly associated with higher change in PSQI scores, after adjusting for family members' age, sex, race/ethnicity, and patient's discharge disposition [ß=0.4 (95% C.I 0.24, 0.48); p<0.01]. Most (n=72, 76%) prioritized interventions supporting information over well-being needs to reduce psychological distress after cardiac arrest. Conclusions: There was a significant decline in sleep health among close family members of cardiac arrest survivors in the acute phase following the event. Psychological distress was associated with this sleep disruption. Further investigation into their temporal associations is needed to develop targeted interventions to support families during this period of uncertainty. WHAT IS KNOWN: Sleep health has been identified as a key element in maintaining cardiovascular health.Close family members of critically ill patients experience suboptimal sleep health and psychological distress may contribute to it. WHAT THE STUDY ADDS: It is breaking new ground in understanding the sleep health dynamics of close family members of cardiac arrest survivors, a critical but often overlooked group of caregivers.The study highlights significant associations between psychological distress and poor sleep that further deteriorates within the first month after a loved one's cardiac arrest.Families of cardiac arrest survivors expressed a high priority for information-based interventions to help alleviate psychological distress during the initial month following the cardiac event emphasizing the need for targeted, accessible, resources to address their psychological and potentially sleep-related challenges.

Nutritional support in pancreatic cancer patients and its effect on nutritional status: an observational regional HPB network study investigating current practice.

PURPOSE: Preoperative malnutrition is associated with poor postoperative outcomes in patients with pancreatic cancer. This study evaluated the effectiveness of current practice in nutritional support for patients with pancreatic cancer. METHODS: Observational multicenter HPB network study conducted at the Isala Clinics Zwolle, Medical Spectrum Twente, Medical Center Leeuwarden, and University Medical Center Groningen between October 2021 and May 2023. Patients with a suspected pancreatic malignancy scheduled for surgery were screened for malnutrition using the Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and referred to a dedicated dietician for nutritional support comprising pancreatic enzyme replacement therapy, dietary advice, and nutritional supplements to achieve adequate caloric and protein intake. At baseline, 1 day preoperatively, and 3 months postoperatively, the nutritional status and muscle thickness were evaluated. RESULTS: The study included 30 patients, of whom 12 (40%) classified as malnourished (PG-SGA ≥ 4) at baseline. Compared to well-nourished patients, malnourished patients were younger, were predominantly female, and had a higher body mass index, despite having lost more body weight in the past 6 months. All malnourished patients and 78% of the well-nourished patients received nutritional support. Consequently, a preoperative increase in caloric and protein intake and body weight were observed. Postoperatively, despite a further increase in caloric intake, a considerable decrease in protein intake, body weight, and muscle thickness was observed. CONCLUSION: Malnutrition is prevalent in patients undergoing pancreatic surgery. Nutritional support by a dedicated dietician is effective in enhancing patients' preoperative nutritional status. However, postoperative monitoring of adequate nutritional intake in patients could be improved.

MethParquet: an R package for rapid and efficient DNA methylation association analysis adopting Apache Parquet.

SUMMARY: Genome-wide DNA methylation (DNAm) profiling is indispensable for unveiling how DNAm regulates biological pathways and individual phenotypes. However, managing and analyzing extensive DNAm data generated from large cohort studies present computational obstacles. Apache Parquet is a data file format that allows for efficient data storage, retrieval, and manipulation, alleviating computational hurdles associated with conventional row-based formats. We here introduce MethParquet, the first R package leveraging the columnar Parquet format for efficient DNAm data analysis. It can be used for data extraction, methylation risk score calculation, epigenome-wide association analyses, and other standard post-quality control tasks. The package flexibly implements diverse regression models. Via a public methylation dataset, we show the efficiency of this package in reducing running time and RAM usage in large-scale EWAS. AVAILABILITY AND IMPLEMENTATION: The MethParquet R package is publicly available on the GitHub repository https://github.com/ZWangTen/MethParquet. It includes a vignette and a toy dataset derived from a public resource.

Vertebrate and invertebrate animal infection models of Candida auris pathogenicity.

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies using mice, the definitive model, are inconsistent due to differences in mouse and fungal strains, immunosuppressive regimes, doses, and outcome metrics. At the same time, developing models of skin colonization present a route to new insights into an aspect of fungal pathogenesis that has not been well studied in other species. We also discuss the growing use of nonmammalian model systems, including both vertebrates and invertebrates, such as zebrafish, C. elegans, Drosophila, and Galleria mellonella, that have been productively employed in virulence studies with other fungal species. This review will discuss progress in developing appropriate animal models, outline current challenges, and highlight opportunities in demystifying this curious species.

Systematic Transcriptome Profiling of hPSC-derived Osteoblasts Unveils CORIN's Mastery in Governing Osteogenesis Through CEBPD Modulation.

The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect hPSC-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide ChIP enrichment and mechanistic studies show that p38 MAPK-mediated CEBPD upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in MSCs exerts a negative regulatory effect on osteogenesis through a similar mechanism. ChIP-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.

Short-Term Impact of Seizures and Mitigation Opportunities.

PURPOSE OF REVIEW: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus. RECENT FINDINGS: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures. Primary outcomes included those related to short-term burdens of seizures and the benefits of acute treatments to reduce short-term burdens. Of the 1332 articles identified through PubMed and 17 through other sources, 27 had relevant outcomes and were included in the qualitative synthesis. Seizure emergencies negatively affected short-term quality of life and the ability to conduct normal daily living activities and were associated with physical (injury) and financial (emergency transport, hospitalization) burdens. The use of acute treatment was associated with a rapid return (≤ 1 h) to normal function/self for both patients and caregivers and potentially lower healthcare utilization and costs. Seizure action plans may improve knowledge and comfort with seizure care, empowering patients and caregivers. The short-term burden of seizures can create a substantial negative impact on patients and caregivers. Acute treatments may reduce the short-term burdens of seizures in addition to their well-described role to reduce seizure activity and the risk for status epilepticus.

Outcomes of oocyte retrievals completed by reproductive endocrinology and infertility fellows versus faculty: a 7-year retrospective review.

PURPOSE: To examine outcomes of oocyte retrievals completed by Reproductive Endocrinology and Infertility (REI) fellows versus faculty physicians. METHODS: This retrospective cohort study examined patients who underwent oocyte retrievals at Mayo Clinic from July 15, 2009, to December 15, 2016. The primary outcome was the oocyte retrieval rate (ORR) calculated per retrieval as the number of oocytes retrieved per follicles aspirated. The Wilcoxon signed-rank test was used to compare follicle and oocyte counts and ORR between fellows and faculty during the same bilateral retrieval. RESULTS: The study cohort included the first bilateral retrieval from 845 unique patients completed by 11 fellows and seven faculty. The median ORR was not statistically different for fellows and faculty (0.79 versus 0.80, p = 0.46). To assess for a learning curve, the outcomes of seven fellows who completed at least 80 retrievals in their first year were examined as four chronologically ordered sets of 20. When these sets were compared to the faculty physician mean ORR, no significant differences were found (p-values of 0.69, 0.69, 0.81, and 0.81, respectively). CONCLUSION: There were no significant differences in oocyte retrieval rates between fellows versus faculty over a 7-year period, with no significant learning curve observed. These findings suggest that fellows possess the requisite skills for successful oocyte retrieval upon entering REI fellowship following their OB/GYN residency. However, this does not diminish the critical role of comprehensive fellowship training and close supervision, especially in initial and complex cases.

Pharmacologic Activation of Integrated Stress Response Kinases Inhibits Pathologic Mitochondrial Fragmentation.

Excessive mitochondrial fragmentation is associated with the pathologic mitochondrial dysfunction implicated in the pathogenesis of etiologically-diverse diseases, including many neurodegenerative disorders. The integrated stress response (ISR) - comprising the four eIF2α kinases PERK, GCN2, PKR, and HRI - is a prominent stress-responsive signaling pathway that regulates mitochondrial morphology and function in response to diverse types of pathologic insult. This suggests that pharmacologic, stress-independent activation of the ISR represents a potential strategy to mitigate pathologic mitochondrial fragmentation associated with human disease. Here, we show that pharmacologic, stress-independent activation of the ISR kinases HRI or GCN2 promotes adaptive mitochondrial elongation and prevents mitochondrial fragmentation induced by the calcium ionophore ionomycin. Further, we show that stress-independent activation of these ISR kinases reduces mitochondrial fragmentation and restores basal mitochondrial morphology in patient fibroblasts expressing the pathogenic D414V variant of the pro-fusion mitochondrial GTPase MFN2 associated with neurological dysfunctions including ataxia, optic atrophy, and sensorineural hearing loss. These results identify pharmacologic, stress-independent activation of ISR kinases as a potential strategy to prevent pathologic mitochondrial fragmentation induced by disease-relevant chemical and genetic insults, further motivating the pursuit of highly selective ISR kinase-activating compounds as a therapeutic strategy to mitigate mitochondrial dysfunction implicated in diverse human diseases.

Preconception health and care policies, strategies and guidelines in the UK and Ireland: a scoping review.

BACKGROUND: Preconception health has the potential to improve parental, pregnancy and infant outcomes. This scoping review aims to (1) provide an overview of the strategies, policies, guidelines, frameworks, and recommendations available in the UK and Ireland that address preconception health and care, identifying common approaches and health-influencing factors that are targeted; and (2) conduct an audit to explore the awareness and use of resources found in the scoping review amongst healthcare professionals, to validate and contextualise findings relevant to Northern Ireland. METHODS: Grey literature resources were identified through Google Advanced Search, NICE, OpenAire, ProQuest and relevant public health and government websites. Resources were included if published, reviewed, or updated between January 2011 and May 2022. Data were extracted into Excel and coded using NVivo. The review design included the involvement of the "Healthy Reproductive Years" Patient and Public Involvement and Engagement advisory panel. RESULTS: The searches identified 273 resources, and a subsequent audit with healthcare professionals in Northern Ireland revealed five additional preconception health-related resources. A wide range of resource types were identified, and preconception health was often not the only focus of the resources reviewed. Resources proposed approaches to improve preconception health and care, such as the need for improved awareness and access to care, preconceptual counselling, multidisciplinary collaborations, and the adoption of a life-course approach. Many behavioural (e.g., folic acid intake, smoking), biomedical (e.g., mental and physical health conditions), and environmental and social (e.g., deprivation) factors were identified and addressed in the resources reviewed. In particular, pre-existing physical health conditions were frequently mentioned, with fewer resources addressing psychological factors and mental health. Overall, there was a greater focus on women's, rather than men's, behaviours. CONCLUSIONS: This scoping review synthesised existing resources available in the UK and Ireland to identify a wide range of common approaches and factors that influence preconception health and care. Efforts are needed to implement the identified resources (e.g., strategies, guidelines) to support people of childbearing age to access preconception care and optimise their preconception health.

One health in the Philippines: A review and situational analysis.

The Philippines faces a complex and interconnected web of human, animal, and environmental health issues, including zoonotic and reverse zoonotic diseases, antimicrobial resistance, food insecurity and contamination, and threats from environmental degradation. This paper examines these issues, existing interventions, and their implementation challenges. The overall framework used to analyze the level of operationalization of the One Health approach is the Multi-sectoral One Health Coordination Framework developed by the World Health Organization, Food and Agriculture Organization, and the World Organization for Animal Health. A two-step process was conducted: literature review, followed by consultations with government and non-government stakeholders across national, subnational, and local levels. There has been significant progress in laying the foundation for collaboration between the human, animal, and environmental sectors. These are demonstrated by the presence of structures and systems, including inter-agency task forces, emergency response plans and mechanisms, and a network for health human resources. However, these are eclipsed by challenges, including the limited governance mechanisms within inter-agency committees, fragmented risk assessment and surveillance, untapped opportunities for joint investigation and response, insufficient resources for capacity-building, and absence of comprehensive risk communication and community engagement initiatives. These challenges highlight the importance of promoting multi-sectoral governance and ensuring resource allocation and sharing. Joint activities across risk assessment, surveillance, investigation, and response are critical in ensuring a proactive and holistic approach to addressing threats. A well-capacitated interdisciplinary workforce, not only capable of managing these hazards but also empowering communities to protect themselves, is necessary in ensuring innovation and collaboration on health risks at the human-animal-environment interface. In light of the multifaceted challenges faced by the Philippines, the One Health approach emerges as a vital strategy. By addressing governance issues, enhancing coordination, and bolstering resource allocation, the country can better protect the health and well-being of its people, animals, and ecosystems.

Cross-border mobility in the Meuse-Rhine Euroregion: impact of COVID-19 border restrictions on everyday activities and visiting social network members.

Introduction: Cross-border mobility (CBM) to visit social network members or for everyday activities is an important part of daily life for citizens in border regions, including the Meuse-Rhine Euroregion (EMR: neighboring regions from the Netherlands, Belgium, and Germany). We assessed changes in CBM during the COVID-19 pandemic and how participants experienced border restrictions. Methods: Impact of COVID-19 on the EMR' is a longitudinal study using comparative cross-border data collection. In 2021, a random sample of the EMR-population was invited for participation in online surveys to assess current and pre-pandemic CBM. Changes in CBM, experience of border restrictions, and associated factors were analyzed using multinomial and multivariable logistic regression analysis. Results: Pre-pandemic, 82% of all 3,543 participants reported any CBM: 31% for social contacts and 79% for everyday activities. Among these, 26% decreased social CBM and 35% decreased CBM for everyday activities by autumn 2021. Negative experience of border restrictions was reported by 45% of participants with pre-pandemic CBM, and was higher (p < 0.05) in Dutch participants (compared to Belgian; aOR= 1.4), cross-border [work] commuters (aOR= 2.2), participants with cross-border social networks of friends, family or acquaintances (aOR= 1.3), and those finding the measures 'limit group size' (aOR= 1.5) and 'minimalize travel' (aOR= 2.0) difficult to adhere to and finding 'minimalize travel' (aOR= 1.6) useless. Discussion: CBM for social contacts and everyday activities was substantial in EMR-citizens, but decreased during the pandemic. Border restrictions were valued as negative by a considerable portion of EMR-citizens, especially when having family or friends across the border. When designing future pandemic control strategies, policy makers should account for the negative impact of CBM restrictions on their citizens.

An Evaluation of the Performance, Patient Acceptability and Feasibility of a Point-of-Care HIV-Syphilis Assay in an Urban Emergency Department.

BACKGROUND: Point-of-care (POC) tests for sexually transmitted infections (STIs) permit delivery of results during the patient's emergency department (ED) encounter. We evaluated performance, patient acceptability, and feasibility of a new duplex POC test, Chembio DPP® HIV-Syphilis Assay in an urban ED setting. METHODS: Convenience sampling approach prioritizing those considered at increased risk for an STI and/or with a history of HIV. For the performance evaluation, participants were tested for HIV/syphilis with the Chembio POC assay, and the reference laboratory tests; sensitivity and specificity were determined. For the patient acceptability evaluation, participants completed pre- and post-user surveys. For the feasibility evaluation, ED clinical technicians completed a survey evaluating their perceptions regarding feasibility of use of this POC test. RESULTS: 327 patients were consented and enrolled. The diagnostic sensitivity and specificity of the Chembio POC assay for HIV was 96.5% (95% CI: 90.1%, 99.3%) and 99.6% (95% CI: 97.7%, 100.0%), respectively, and for syphilis was 93.9% (95% CI: 85.0%, 98.3%) and 99.6% (95% CI: 97.9%, 100.0%), respectively. Regarding patient acceptability: 87% trusted the result; and 93% reported they were more likely to seek treatment if they received a positive STI test result in the ED rather than after the ED visit. Regarding feasibility: 90% of the technicians reported they would recommend using the test in EDs. CONCLUSIONS: The Chembio DPP® HIV-Syphilis POC assay had excellent performance characteristics when evaluated in an ED population, as well as high perceived acceptability from patients, and feasibility for ED use from clinical technicians. The test may have utility for HIV-syphilis screening among high-risk ED patients.

Nationwide trends of balloon pulmonary angioplasty and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (2012-2019).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of a pulmonary embolus that occurs in approximately 1%-3% of patients. Pulmonary thromboendoarterectomy (PTE) can be a curative procedure, but balloon pulmonary angioplasty (BPA) has emerged as an option for poor surgical candidates. We used the National Inpatient Sample to query patients who underwent PTE or BPA between 2012 and 2019 with CTEPH. The primary outcome was a composite of in-hospital mortality, myocardial infarction, stroke, tracheostomy, and prolonged mechanical ventilation. Outcomes were compared between low- and high-volume centers, defined as 5 and 10 procedures per year for BPA and PTE, respectively. During our study period, 870 BPA and 2395 PTE were performed. There was a 328% relative increase in the number of PTE performed during the study period. Adverse events for BPA were rare. There was an increase in the primary composite outcome for low-volume centers compared to high-volume centers for PTE (24.4% vs. 12.1%, p = 0.003). Patients with hospitalizations for PTE in low-volume centers were more likely to have prolonged mechanical ventilation (20.0%% vs. 7.2%, p < 0.001) and tracheostomy (7.8% vs. 2.6%, p = 0.017). In summary, PTE rates have been rising over the past 10 years, while BPA rates have remained stable. While adverse outcomes are rare for BPA, patients with hospitalizations at low-volume centers for PTE were more likely to have adverse outcomes. For patients undergoing treatment of CTEPH with BPA or PTE, referral to high-volume centers with multidisciplinary teams should be encouraged for optimal outcomes.

Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management.

A Novel REBOA Training Curriculum for Emergency Medicine Residents: A Pilot Study.

BACKGROUND: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a potentially life-saving intervention to treat noncompressible torso hemorrhage. Traditionally, REBOA use has been limited to surgeons. However, emergency physicians are often the first point-of-contact and are well-versed in obtaining rapid vascular access and damage control resuscitation, making them ideal candidates for REBOA training. STUDY OBJECTIVES: To fill this gap, we designed and evaluated a REBOA training curriculum for emergency medicine (EM) residents. METHODS: Participants enrolled in an accredited 4-year EM residency program (N = 11) completed a 12-hour REBOA training course. Day 1 included lectures, case studies, and hands-on training using REBOA task trainers and perfused cadavers. Day 2 included additional practice and competency evaluations. Assessments included a 25-item written knowledge exam, decision-making on case studies, REBOA placement success, and time-to-placement. Participants returned at 4 months to assess long-term retention. Data were analyzed using t-tests and nonparametric statistics at p < 0.05. RESULTS: Scores on a 25-item multiple choice test significantly increased from pre-training (65% ± 5%) to post-training (92% ± 1%), p < 0.001. On Day 2, participants scored 100% on correct recognition of REBOA indications and scored 100% on correct physical placement of REBOA. Exit surveys indicated increased preparedness, confidence, and support for incorporating this course into EM training. Most importantly, REBOA knowledge, correct recognition of REBOA indications, and correct REBOA placement skills were retained by the majority of participants at 4 months. CONCLUSION: This course effectively teaches EM residents the requisite skills for REBOA competence and proper placement. This study could be replicated at other facilities with larger, more diverse samples, aiming to expand the use of REBOA in emergency physicians and reducing preventable deaths in trauma.

Examining treatment strategies for xanthelasma palpebrarum: a comprehensive literature review of contemporary modalities.

Xanthelasma palpebrarum (XP) is the predominant form of cutaneous xanthoma, as it accounts for greater than 95% of cases. It is characterized by the presence of foam cell clusters containing a large amount of low-density lipoprotein (LDL), which are located in the connective tissue of skin, tendons, and fascia. XP lesions commonly present as distinctive yellow-orange macules, papules, or nodules, and are primarily on the upper eyelids as well as the inner canthus. Women are affected twice as often as men, with lesions typically emerging between the ages of 35 and 55. The pathophysiology of XP involves abnormal lipid metabolism and is often associated with hyperlipidemic states like Type II and IV hyperlipidemia, hypothyroidism, weight gain, and fatty diet. Despite the availability of various treatment methods, current XP management lacks standardization, particularly due to limited comparative research. To address this gap, we conducted an extensive literature review of 45 studies published between 2012 to 2023, which provides an updated overview of current XP treatment modalities. This comprehensive analysis will inform researchers and clinicians on the evolving landscape of XP management.

Role of ethanolamine utilization and bacterial microcompartment formation in Listeria monocytogenes intracellular infection.

Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host cells. Unlike what was previously observed for S. Typhimurium, in LMO, an EA regulator mutant (ΔeutV) was equally deficient in intracellular replication compared to an EA metabolism mutant (ΔeutB), and this was consistent across Caco-2, RAW 264.7, and THP-1 cell lines. The structural genes encode proteins that self-assemble into bacterial microcompartments (BMCs) that encase the enzymes necessary for EA metabolism. For the first time, native EUT BMCs were fluorescently tagged, and EUT BMC formation was observed in vitro and in vivo. Interestingly, BMC formation was observed in bacteria infecting Caco-2 cells, but not the macrophage cell lines. Finally, the cellular immune response of Caco-2 cells to infection with eut mutants was examined, and it was discovered that ΔeutB and ΔeutV mutants similarly elevated the expression of inflammatory cytokines. In conclusion, EA sensing and utilization during LMO intracellular infection are important for optimal LMO replication and immune evasion but are not always concomitant with BMC formation.IMPORTANCEListeria monocytogenes (LMO) is a bacterial pathogen that can cause severe disease in immunocompromised individuals when consumed in contaminated food. It can replicate inside of mammalian cells, escaping detection by the immune system. Therefore, understanding the features of this human pathogen that contribute to its infectiousness and intracellular lifestyle is important. In this work we demonstrate that genes encoding both regulators and enzymes of EA metabolism are important for optimal growth inside mammalian cells. Moreover, the formation of specialized compartments to enable EA metabolism were visualized by tagging with a fluorescent protein and found to form when LMO infects some mammalian cell types, but not others. Interestingly, the formation of the compartments was associated with features consistent with an early stage of the intracellular infection. By characterizing bacterial metabolic pathways that contribute to survival in host environments, we hope to positively impact knowledge and facilitate new treatment strategies.

Untargeted Metabolome Atlas for Sleep Phenotypes in the Hispanic Community Health Study/Study of Latinos.

Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep phenotypes and blood metabolites. Utilizing data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep phenotypes, grouped in several domains (i.e., sleep disordered breathing (SDB), sleep duration, timing, insomnia symptoms, and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualize and interpret the associations between sleep phenotypes and metabolites. The patterns of statistically significant associations between sleep phenotypes and metabolites differed by superpathways, and highlighted subpathways of interest for future studies. For example, some xenobiotic metabolites were associated with sleep duration and heart rate phenotypes (e.g. 1H-indole-7-acetic acid, 4-allylphenol sulfate), while ketone bodies and fatty acid metabolism metabolites were associated with sleep timing measures (e.g. 3-hydroxybutyrate (BHBA), 3-hydroxyhexanoylcarnitine (1)). Heart rate phenotypes had the overall largest number of detected metabolite associations. Many of these associations were shared with both SDB and with sleep timing phenotypes, while SDB phenotypes shared relatively few metabolite associations with sleep duration measures. A number of metabolites were associated with multiple sleep phenotypes, from a few domains. The amino acids vanillylmandelate (VMA) and 1-carboxyethylisoleucine were associated with the greatest number of sleep phenotypes, from all domains other than insomnia. This atlas of sleep-metabolite associations will facilitate hypothesis generation and further study of the metabolic underpinnings of sleep health.

Video-assisted thoracic surgery and robotic-assisted first-rib excision and thoracic outlet syndrome decompression.

Multiple surgical approaches have been used in the management of thoracic outlet syndrome. These approaches have traditionally been "open" approaches and have been associated with the inherent morbidities of an open approach, including a risk of injury to the neurovascular structures due to traction and trauma while resecting the first rib. In addition, there has been concern that recurrence of symptoms may be related to incomplete resection of the rib with conventional open techniques. With the advent of minimally invasive thoracic surgery, surgeons began to explore first-rib resection via a thoracoscopic approach. Unfortunately, the existing video-assisted thoracic surgery technology and equipment was not well suited to working in the apex of the chest. With the introduction and subsequent progress in robotic surgery and instrumentation, this dissection can be performed with all the advantages of robotics, but also with minimal traction and trauma to the neurovascular structures, and incorporates almost complete resection of the rib with minimal residual stump. Robotics has developed as a reliable, safe, and less invasive approach to first-rib resection, yielding excellent results while limiting the morbidity of the procedure.