The Discovery of XY Sex Chromosomes in a \u3cem\u3eBoa\u3c/em\u3e and \u3cem\u3ePython\u3c/em\u3e

For over 50 years, biologists have accepted that all extant snakes share the same ZW sex chromosomes derived from a common ancestor [1, 2, 3], with different species exhibiting sex chromosomes at varying stages of differentiation. Accordingly, snakes have been a well-studied model for sex chromosome evolution in animals [1, 4]. A review of the literature, however, reveals no compelling support that boas and pythons possess ZW sex chromosomes [2, 5]. Furthermore, phylogenetic patterns of facultative parthenogenesis in snakes and a sex-linked color mutation in the ball python (Python regius) are best explained by boas and pythons possessing an XY sex chromosome system [6, 7]. Here we demonstrate that a boa (Boa imperator) and python (Python bivittatus) indeed possess XY sex chromosomes, based on the discovery of male-specific genetic markers in both species. We use these markers, along with transcriptomic and genomic data, to identify distinct sex chromosomes in boas and pythons, demonstrating that XY systems evolved independently in each lineage. This discovery highlights the dynamic evolution of vertebrate sex chromosomes and further enhances the value of snakes as a model for studying sex chromosome evolution

Health Care Use and Costs Among Patients With Nonalcoholic Steatohepatitis With Advanced Fibrosis Using the Fibrosis-4 Score

Limited evidence exists on the clinical and economic burden of advanced fibrosis in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) due to the invasiveness of liver biopsies for accurately staging liver disease. The fibrosis-4 (FIB-4) score allows for noninvasive assessment of liver fibrosis by using clinical and laboratory data alone. This study aimed to characterize the comorbidity burden, health care resource use (HCRU), and costs among patients with NAFLD/NASH with FIB-4-defined F3 (bridging fibrosis) and F4 (compensated cirrhosis) fibrosis. Using the Optum Research Database, a retrospective cohort study was conducted among 251,725 commercially insured adult patients with ≥1 NAFLD/NASH diagnosis from January 1, 2008, to August 31, 2016, and laboratory data required to calculate FIB-4 scores. Five criteria using varying FIB-4 score cutoffs were identified based on expert clinical opinion and published literature. Date of the first valid FIB-4 score marked the index date. Mean annual HCRU and costs were calculated during the pre-index and post-index periods. The prevalence of FIB-4-based F3 and F4 fibrosis was 0.40%-2.72% and 1.03%-1.61%, respectively. Almost 50% of patients identified with FIB-4-based F3 or F4 had type 2 diabetes, cardiovascular disease, or renal impairment. Total all-cause health care costs increased significantly from pre-index to post-index for patients with FIB-4-based F3 fibrosis across most criteria (17%-29% increase) and patients with FIB-4-based F4 fibrosis across all criteria (47%-48% increase). Inpatient costs were the primary drivers of this increment

Hepatitis B e antigen status and hepatitis B DNA levels in women of childbearing age with chronic hepatitis B infection screening for clinical trials

BACKGROUND: Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. AIM: To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. METHODS: Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18-69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. RESULTS: Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p CONCLUSIONS: Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load

Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol-related liver disease

BACKGROUND: Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. METHODS: Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. RESULTS: Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P \u3c .05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR = 2.86; 95%CI 1.67-4.97). CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease

Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. \u27Recommended monitoring\u27 was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the \u27definite\u27 category, and 34.1% (208/610 patients) in the \u27equivocal\u27 category, of whom 109 moved up to \u27definite\u27 status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in \u27definite\u27 patients. Routine monitoring rates were high prior to treatment in \u27definite/ treated\u27 patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in \u27definite/ untreated\u27 patients (ALT: 48%; DNA: 32%). Among \u27equivocal/ treated\u27 patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among \u27treatment ineligible\u27 patients was similar to those in the \u27equivocal\u27 and untreated \u27definite\u27 groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with \u27definite\u27 indications for antiviral therapy remained untreated

The Radial Distribution of the Interstellar Medium in Disk Galaxies: Evidence for Secular Evolution

One possible way for spiral galaxies to internally evolve would be for gas to flow to the center and form stars in a central disk (pseudo-bulge). If the inflow rate is faster than the rate of star formation, a central concentration of gas will form. In this paper we present radial profiles of stellar and 8 μm emission from polycyclic aromatic hydrocarbons (PAHs) for 11 spiral galaxies to investigate whether the interstellar medium in these galaxies contains a central concentration above that expected from the exponential disk. In general, we find that the two-dimensional CO and PAH emission morphologies are similar, and that they exhibit similar radial profiles. We find that in 6 of the 11 galaxies there is a central excess in the 8 μm and CO emission above the inward extrapolation of an exponential disk. In particular, all four barred galaxies in the sample have strong central excesses in both 8 μm and CO emission. These correlations suggest that the excess seen in the CO profiles is, in general, not simply due to a radial increase in the CO emissivity. In the inner disk, the ratio of the stellar to the 8 μm radial surface brightness is similar for 9 of the 11 galaxies, suggesting a physical connection between the average stellar surface brightness and the average gas surface brightness at a given radius. We also find that the ratio of the CO to 8 μm PAH surface brightness is consistent over the sample, implying that the 8 μm PAH surface brightness can be used as an approximate tracer of the interstellar medium

Cardiovascular implications and physical activity in middle-aged and older adults with a history of COVID-19 (CV COVID)::a protocol for a randomised controlled trial

Background: The clinical manifestation of COVID-19 is associated with infection and inflammation of the lungs, but there is evidence to suggest that COVID-19 may also affect the structure and function of the cardiovascular system. At present, it is not fully understood to what extent COVID-19 impacts cardiovascular function in the short- and long-term following infection. The aim of the present study is twofold: (i) to define the effect of COVID-19 on cardiovascular function (i.e. arterial stiffness, cardiac systolic and diastolic function) in otherwise healthy individuals and (ii) to evaluate the effect of a home-based physical activity intervention on cardiovascular function in people with a history of COVID-19. Methods: This prospective, single-centre, observational study will recruit 120 COVID-19-vaccinated adult participants aged between 50 and 85 years, i.e. 80 with a history of COVID-19 and 40 healthy controls without a history of COVID-19. All participants will undergo baseline assessments including 12-lead electrocardiography, heart rate variability, arterial stiffness, rest and stress echocardiography with speckle tracking imaging, spirometry, maximal cardiopulmonary exercise testing, 7-day physical activity and sleep measures and quality of life questionnaires. Blood samples will be collected to assess the microRNA expression profiles, cardiac and inflammatory biomarkers, i.e. cardiac troponin T; N-terminal pro B-type natriuretic peptide; tumour necrosis factor alpha; interleukins 1, 6 and 10; C-reactive protein; d-dimer; and vascular endothelial growth factors. Following baseline assessments, COVID-19 participants will be randomised 1:1 into a 12-week home-based physical activity intervention aiming to increase their daily number of steps by 2000 from baseline. The primary outcome is change in left ventricular global longitudinal strain. Secondary outcomes are arterial stiffness, systolic and diastolic function of the heart, functional capacity, lung function, sleep measures, quality of life and well-being (depression, anxiety, stress and sleep efficiency). Discussion: The study will provide insights into the cardiovascular implications of COVID-19 and their malleability with a home-based physical activity intervention. Trial registration: ClinicalTrials.gov NCT05492552. Registered on 7 April 2022

The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population

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