Angular Head Velocity Cells within Brainstem Nuclei Projecting to the Head Direction Circuit.

The sense of orientation of an animal is derived from the head direction (HD) system found in several limbic structures and depends on an intact vestibular labyrinth. However, how the vestibular system influences the generation and updating of the HD signal remains poorly understood. Anatomical and lesion studies point toward three key brainstem nuclei as key components for generating the HD signal-nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nuclei. Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To determine the types of information these brain areas convey to the HD network, we recorded neurons from these regions while female rats actively foraged in a cylindrical enclosure or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with the angular head velocity (AHV) of the rat. Two fundamental types of AHV cells were observed; (1) symmetrical AHV cells increased or decreased their firing with increases in AHV regardless of the direction of rotation, and (2) asymmetrical AHV cells responded differentially to clockwise and counterclockwise head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV, whereas firing was attenuated in other cells. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed from the vestibular nuclei that are responsible for generating the HD signal.SIGNIFICANCE STATEMENT Extracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of AHV cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated, some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the head of the rat in the azimuthal plane.

Applying a Bayesian Spatiotemporal Model to Examine Excess County-Level Cardiovascular Disease Death Rates During the COVID-19 Pandemic.

Amid the COVID-19 pandemic, national cardiovascular disease (CVD) death rates increased, especially among younger adults. County-level variation has not been documented. Using county-level CVD deaths (ICD-10 codes: I00-I99) from the US National Vital Statistics System, we developed a Bayesian multivariate spatiotemporal model to estimate excess CVD death rates in 2020 based on trends from 2010-2019 for adults aged 35-64 and ≥65 years. Among adults aged 35-64 years, 64.7% of counties experienced significant excess CVD death rates. The median county-level CVD death rate in 2020 was 150 per 100,000 persons, which exceeded the predicted rate for 2020 (median excess death rate: 11 per 100,000; median excess rate ratio: 1.08). Among adults aged ≥65 years, 15.2% of counties experienced significant excess CVD death rates. The median county-level CVD death rate was 1,546 per 100,000 in 2020, which exceeded the predicted rate in 2020 (median excess death rate: 48 per 100,000, median excess rate ratio: 1.03). Counties with significant excess death rates in 2020 were geographically dispersed. In 2020, disruptions of county-level CVD death rates were widespread, especially among younger adults, suggesting the continued importance of CVD prevention and treatment in younger adults in communities across the country.

Wastewater surveillance for bacterial targets: current challenges and future goals.

Wastewater-based epidemiology (WBE) expanded rapidly in response to the COVID-19 pandemic. As the public health emergency has ended, researchers and practitioners are looking to shift the focus of existing wastewater surveillance programs to other targets, including bacteria. Bacterial targets may pose some unique challenges for WBE applications. To explore the current state of the field, the National Science Foundation-funded Research Coordination Network (RCN) on Wastewater Based Epidemiology for SARS-CoV-2 and Emerging Public Health Threats held a workshop in April 2023 to discuss the challenges and needs for wastewater bacterial surveillance. The targets and methods used in existing programs were diverse, with twelve different targets and nine different methods listed. Discussions during the workshop highlighted the challenges in adapting existing programs and identified research gaps in four key areas: choosing new targets, relating bacterial wastewater data to human disease incidence and prevalence, developing methods, and normalizing results. To help with these challenges and research gaps, the authors identified steps the larger community can take to improve bacteria wastewater surveillance. This includes developing data reporting standards and method optimization and validation for bacterial programs. Additionally, more work is needed to understand shedding patterns for potential bacterial targets to better relate wastewater data to human infections. Wastewater surveillance for bacteria can help provide insight into the underlying prevalence in communities, but much work is needed to establish these methods.IMPORTANCEWastewater surveillance was a useful tool to elucidate the burden and spread of SARS-CoV-2 during the pandemic. Public health officials and researchers are interested in expanding these surveillance programs to include bacterial targets, but many questions remain. The NSF-funded Research Coordination Network for Wastewater Surveillance of SARS-CoV-2 and Emerging Public Health Threats held a workshop to identify barriers and research gaps to implementing bacterial wastewater surveillance programs.

Associations between ultra-distal forearm bone mineral density and incident fracture in women.

Bone mineral density measured at the ultra-distal forearm site was associated with any fracture, as well as distal radius fracture in women from a longitudinal cohort study. PURPOSE: Femoral neck (BMDhip) and lumbar spine (BMDspine) bone mineral density (BMD) are routinely used to assess fracture risk. More data are needed to understand how ultra-distal forearm BMD (BMDUDforearm) may assist fracture prediction. METHODS: Using a Lunar DPX-L, Geelong Osteoporosis Study women (n = 1026), aged 40-90 years, had BMD measured. Incident low-trauma fractures were radiologically verified. Using Cox proportional hazard models, hazard ratios (HR) were calculated for BMDUDforearm as a continuous variable (expressed as a one-unit decrease in T-score) and a categorical variable (normal/osteopenia/osteoporosis). Areas under receiver operating characteristics (AUROC) curves were calculated. Analyses were conducted for any fracture and distal radius fractures. RESULTS: During 14,270 person-years of follow-up, there were 318 fractures (85 distal radius). In adjusted models, continuous BMDUDforearm was associated with any (HR 1.26;95%CI 1.15-1.39) and distal radius fractures (HR 1.59;95%CI 1.38-1.83). AUROCs for continuous BMDUDforearm, 33% forearm(BMD33%forearm), BMDhip, BMDspine, and FRAX without BMD were similar for any fracture (p > 0.05). For distal radius fracture, the AUROC for BMDUDforearm was higher than other sites and FRAX (p < 0.05). In adjusted models, those with osteoporosis had a higher likelihood of any fracture (HR 2.12; 95%CI 1.50-2.98). For distal radius fractures, both osteopenia and osteoporosis had a higher risk (HR 4.31; 95%CI 2.59-7.15 and 4.81; 95%CI 2.70-8.58). AUROCs for any fracture were similar for categorical BMD at all sites but lower for FRAX (p < 0.05). For distal radius fractures, the AUROC for BMDUDforearm, was higher than other sites and FRAX (p < 0.05). CONCLUSION: Ultra-distal forearm BMD may aid risk assessments for any distal radius fractures.

Highly Sensitive and Selective Recognition of Zn2⁺ and Fe2⁺ Ions Using a Novel Thiophene-Derived Hydrazone Dual Fluorometric Sensor.

The selective detection of Zn2⁺ and Fe2⁺ ions is critical in environmental and biological studies. Schiff base chemosensors hold promise, but exploration of thiophene-derived variants remains limited. This work introduces a novel thiophene-derived Schiff base sensor (TBH), synthesized through the condensation reaction of thiophene-2-carboxaldehyde with benzil-bis-hydrazone, for the selective detection of Zn2⁺ and Fe2⁺ ions. TBH exhibits remarkable selectivity, with a significant 185-fold fluorescence enhancement for Zn2⁺ and complete quenching 99% for Fe2⁺, allowing for distinct detection of both ions. Notably, TBH demonstrates high binding affinity towards Zn2⁺ and Fe2⁺, even in the presence of competing cations, forming stable 1:1 complexes. This finding is supported by absorption and emission titration studies and FT-IR analysis as well. This easily synthesized, rapid and cost-effective sensor offers a promising approach for sensitive and differentiated dual detection of Zn2⁺ and Fe2⁺ in environmental and biological systems.

The association of religion with advance care planning.

Personal preferences influence end-of-life (EOL) decision-making and are commonly associated with engagement in the advance care planning process. Completing an advance directive (AD) allows individuals to formally document and legally report their EOL care preferences. This study explored how two aspects of religion-personal religious beliefs and formal religion practices-may be associated with advance care planning. A national sample of healthy adults in the United States aged 50 years and older (n = 514; 74% cisgender women) completed surveys detailing their EOL preferences, advance care planning, personal religious beliefs, and formal religion practices. Using Ordinary Least Squares (OLS), we find that a higher belief in God's role at EOL was associated with a higher preference for life-prolonging measures. Using logistic regression, those with a higher belief in God's role at EOL had lower odds of AD completion. Multiple dimensions of religion should be considered when studying health care preferences and decision-making.

Ancient fish lineages illuminate toll-like receptor diversification in early vertebrate evolution.

Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate RAG- mediated adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here, we investigate the diversification of vertebrate toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the RAG-mediated adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively, these results provide an unparalleled perspective of TLR diversity and offer a ready framework for testing gene annotations in non-model species.

Lipopolysaccharide-binding protein and bone health: data from a population-based sample of men.

We aimed to investigate the association between serum lipopolysaccharide-binding protein (LBP) and bone health in men. LBP was associated with lower bone density at the mid-forearm and the quantitative heel ultrasound measure, broadband ultrasound attenuation, for heavier participants. Data do not support clear associations between serum LBP and bone health. INTRODUCTION: The objective of this study was to investigate the association between serum lipopolysaccharide-binding protein (LBP) and potential downstream effects on skeletal density, quality, and turnover in a population-based sample of men. METHODS: This cross-sectional study utilised data from 1149 men (aged 20-96 year) enrolled in the Geelong Osteoporosis Study. Blood samples were obtained and lipopolysaccharide-binding protein (LBP), bone resorption marker, C-telopeptide (CTx), and formation marker, type 1 procollagen amino-terminal-propeptide (P1NP), were measured. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Stiffness Index (SI), broadband ultrasound attenuation (BUA), and speed of sound (SOS) were derived from quantitative heel ultrasound (QUS). Linear regression models were developed to test associations between log-transformed LBP (ln-LBP), BMD, QUS, and bone turnover, after adjusting for potential covariates. RESULTS: Serum LBP ranged from 1.07-208.53 ng/mL (median 16.53 ng/mL). Those with higher levels were older, less mobile, and had lower BMD at the mid-forearm, otherwise, groups were similar. Before and after adjustment for age, ln-LBP was associated with lower BMD at the spine, total body, and mid-forearm. Further adjustment for weight attenuated associations at the spine and total body, yet the relationship at the mid-forearm was sustained (ß - 0.014 ± 0.004, p = 0.001). SOS and SI were not associated with ln-LBP either before or after adjustment for age; however, weight was identified as an effect modifier in the relationship between ln-LBP and BUA. An association was observed for those weighing greater than 82.7 kg (ß 3.366 ± 0.929, p < 0.001), after adjustment for potential covariates. Neither bone turnover marker was associated with ln-LBP. CONCLUSION: Our data do not support a clear association between serum LBP and measures of bone health in this sample of men.

Mean Bone Material Strength Index Values for Women are Lower Than Those for Men: Data from a Single Geographical Location.

Bone material strength index (BMSi) values are obtained using impact microindentation, which assesses the ability of bone to resist indentation. Differences in BMSi between men and women are unclear, and to date, BMSi sex differences have not been compared for individuals from the same population. Therefore, we compared BMSi values for men and women drawn from the same geographical location in Australia. Participants (n = 220) were from the Geelong Osteoporosis Study. BMSi was measured, following international published guidelines, using an OsteoProbe for participants at recent follow-up phases (women 2022-2023 and men 2016-2022). Women (n = 55) were age matched to men (n = 165) in a 1:3 ratio. A two-sample t test was used to determine the intergroup difference in mean BMSi. Linear regression was also performed, adjusting for weight and height. Median (IQR) ages for men and women were 67.0 (61.7-71.5) and 67.4 (62.0-71.2) years (p = 0.998). Men were heavier (81.0 ± 10.9 vs 71.0 ± 13.9 kg, p < 0.001) and taller (173.9 ± 6.4 vs 161.5 ± 7.5 cm, p < 0.001) than women. Mean (± SD) BMSi for women (75.7 ± 7.4) was lower than for men (82.8 ± 6.8) (p < 0.001). The difference persisted after adjustment for weight and height (mean ± SE: 76.5 ± 1.1 vs 82.5 ± 0.6, p < 0.001). Given the higher fracture risk observed for women, the higher mean BMSi values in men are consistent with cross sectional data suggesting this measure may be useful in fracture prediction.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Peripheral quantitative computed tomography-derived bone parameters in men with impaired fasting glucose and diabetes.

INTRODUCTION: Individuals with type 2 diabetes mellitus (T2DM) are at higher risk of fracture, but paradoxically do not have reduced bone mineral density. We investigated associations between peripheral quantitative computed tomography (pQCT) and glycaemia status. MATERIALS AND METHODS: Participants were men (n = 354, age 33-92 year) from the Geelong Osteoporosis Study. Diabetes was defined by fasting plasma glucose (FPG) ≥ 7.0 mmol/L, self-report of diabetes and/or antihyperglycaemic medication use and impaired fasting glucose (IFG) as FPG 5.6-6.9 mmol/L. Bone measures were derived using pQCT (XCT2000) at 4% and 66% radial and tibial sites. Linear regression was used, adjusting for age, body mass index and socio-economic status. RESULTS: At the 4% site, men with T2DM had lower adjusted bone total area, trabecular area and cortical area at the radius (all - 6.2%) and tibia (all - 6.4%) compared to normoglycaemia. Cortical density was higher for T2DM at the radius (+ 5.8%) and tibia (+ 8.0%), as well as adjusted total bone density at the tibial site (+ 6.1%). At the 66% site, adjusted total bone area and polar stress strain index were lower for T2DM at the radius (- 4.3% and - 8.0%). Total density was also higher for T2DM (+ 1.2%). Only cortical density at the 4% tibial site was different between IFG and normoglycaemia in adjusted analyses (+ 4.5%). CONCLUSION: Men with T2DM had lower total bone area, trabecular area, cortical area and polar stress strain index than the other two groups; however, total density and cortical density were higher. Only one difference was observed between IFG and normoglycaemia; increased tibial cortical density.

Benzil Bis-Hydrazone Based Fluorescence 'Turn-on' Sensor for Highly Sensitive and Selective Detection of Zn(II) Ions.

In this study, a novel Benzil Bis-Hydrazone (BBH) sensor with two C = N-N = C moieties was designed and synthesized based on the condensation reaction between benzil-dihydrazone (b) and cinnamaldehyde. The BBH probe in dimethylsulfoxide showed extremely weak fluorescence. However, the same solution exhibited an intensive fluorescence enhancement (152-fold) with the introduction of Zn(II) ions. In contrast, no or negligible fluorescence changes were observed when other ions were added. The fluorogenic behavior of BBH towards the examined cations indicated an excellent selectivity of the BBH sensor for Zn(II) cations without any interference from other cations like Fe(II), Mg(II), Cu(II), Co(II), Mn(II), Cr(III), Hg(II), Sn(II), Al(I), La(III), Ca(II), Ba(II), Na(I), K(I), and especially Cd(II). Moreover, the UV-vis spectrophotometric titrations revealed that a 1:1 stoichiometric complex BBH-Zn(II) was formed during the Zn(II) sensing and the binding constant value for this complex was calculated to be equal to 106.8. Further, in order to show the affinity of the BBH sensor for Zn(II) cations, it was deemed necessary to determine the limit of detection (LOD) which was found to equal to 2.5 10-4 M.

Predicting psychosocial risk in pediatric kidney transplantation: An exploratory cluster analysis of a revised Pediatric Transplant Rating Instrument.

BACKGROUND: The Pediatric Transplant Rating Instrument (P-TRI) is a 17-item scale developed to assess psychosocial risk factors for poor outcomes after solid organ transplantation. Research has identified the limitations of the original instrument and proposed revisions to improve clinical utility. This project examined patterns of risk in children being evaluated for kidney transplant using a revised P-TRI. METHODS: A multidisciplinary kidney transplant team revised the P-TRI. A social worker and a psychologist collaboratively completed the modified instrument for 37 children after the psychosocial pretransplant evaluation. Electronic medical records were reviewed for transplant status (transplanted, active waitlist, inactive) 1 year later. Exploratory cluster analyses and chi-square tests examined patterns of risk and correlates with cluster membership. RESULTS: Three clusters were identified. The high-risk group (29.7%) had difficulties with medication and appointment adherence, strained relationships with the medical team, and the presence of parent psychiatric history. The medium-risk group (35.1%) had difficulties with parent knowledge, financial strain, and risk factors for medication nonadherence. The low-risk group (35.1%) demonstrated no difficulties with adherence or financial strain. Clusters were prospectively associated with transplant status, such that those in the high-risk group were less likely to be transplanted within 1 year post-evaluation. CONCLUSIONS: The revised P-TRI demonstrated good construct validity as risk level appeared to be associated with transplant listing status 1 year post-evaluation. These results suggest that standardized pretransplant psychosocial risk assessment tools may have value in optimizing transplant access if they can be paired with targeted, multidisciplinary interventions to address concerns early in the transplant process.

A systematic review of social determinants of health in pediatric organ transplant outcomes.

BACKGROUND: Equitable access to pediatric organ transplantation is critical, although risk factors negatively impacting pre- and post-transplant outcomes remain. No synthesis of the literature on SDoH within the pediatric organ transplant population has been conducted; thus, the current systematic review summarizes findings to date assessing SDoH in the evaluation, listing, and post-transplant periods. METHODS: Literature searches were conducted in Web of Science, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature databases. RESULTS: Ninety-three studies were included based on pre-established criteria and were reviewed for main findings and study quality. Findings consistently demonstrated disparities in key transplant outcomes based on racial or ethnic identity, including timing and likelihood of transplant, and rates of rejection, graft failure, and mortality. Although less frequently assessed, variations in outcomes based on geography were also noted, while findings related to insurance or SES were inconsistent. CONCLUSION: This review underscores the persistence of SDoH and disparity in equitable transplant outcomes and discusses the importance of individual and systems-level change to reduce such disparities.

Association of amnioinfusion volume at the time of surgery for twin-twin transfusion syndrome and latency to delivery.

OBJECTIVE: To evaluate the impact of amnioinfusion and other peri-operative factors on pregnancy outcomes in the setting of Twin-twin transfusion syndrome (TTTS) treated via fetoscopic laser photocoagulation (FLP). METHODS: Retrospective study of TTTS treated via FLP from 2010 to 2019. Pregnancies were grouped by amnioinfusion volume during FLP (<1 L vs. ≥1 L). The primary outcome was latency from surgery to delivery. An amnioinfusion statistic (AIstat) was created for each surgery based on the volume of fluid infused and removed and the preoperative deepest vertical pocket. Regression analysis was planned to assess the association of AIstat with latency. RESULTS: Patients with amnioinfusion of ≥1 L at the time of FLP had decreased latency from surgery to delivery (61 ± 29.4 vs. 73 ± 28.8 days with amnioinfusion <1 L, p < 0.001) and increased preterm prelabor rupture of membranes (PPROM) <34 weeks (44.7% vs. 33.5%, p = 0.042). Amnioinfusion ≥1 L was associated with an increased risk of delivery <32 weeks (aRR 2.6, 95% CI 1.5-4.5), 30 weeks (aRR 2.4, 95% CI 1.5-3.8), and 28 weeks (aRR 1.9, 95% CI 1.1-2.3). Cox-proportional regression revealed that AIstat was inversely associated with latency (HR 1.1, 95% CI 1.1-1.2). CONCLUSION: Amnioinfusion ≥1 L during FLP was associated with decreased latency after surgery and increased PPROM <34 weeks.

Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers.

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9-79.1), range 50.0-96.6 yr; 574 women, median age 65.5 yr (58.1-75.4), range 50.1-94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2-13.2) and 10.9(6.3-11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00-2.37; 1.90, 1.18-3.05; 2.15, 1.26-3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34-5.29) and adjusted (2.03, 1.01-4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07-2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74-2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.

Fatty Liver Index and Skeletal Muscle Density.

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33-96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.

Transcobalamin receptor deficiency in seven asymptomatic patients ascertained through newborn screening.

We report seven cases from our clinic with transcobalamin receptor deficiency (TCRD). None of our cases have experienced health issues or metabolic decompensation. All have experienced typical growth and development throughout childhood, with our oldest case now 10 years old. Every case has had normalization of initial biochemical abnormalities following parenteral hydroxocobalamin administration. Several cases had trace elevations of methylmalonic acid throughout childhood, all which normalized without further hydroxocobalamin administration. Population data from our state's newborn screening program suggest the incidence of TCRD is comparable to other metabolic disorders associated with elevations of C3 acylcarnitine including propionic academia, isolated methylmalonic academia and combined methylmalonic academia and hyperhomocysteinemia due to cobalamin metabolism disorders. Based on the generally benign nature of this condition, we assert that TCRD may be considered an incidental finding on newborn screen. However, additional long-term data are needed to ascertain the long term outcomes of children identified with TCRD.

Fetal and Neonatal Reticulocyte Count Response to Intrauterine Transfusion for the Treatment of Red Blood Cell Alloimmunization.

Management of hemolytic disease of the fetus and newborn relies on monitoring of maternal antibody titers, fetal ultrasound, and fetal middle cerebral artery peak systolic velocity studies and is generally treated by intrauterine transfusion (IUT). Few studies have explored fetal and neonate physiological responses to IUT. Our objective was to examine fetal erythropoietic response and to examine neonatal erythropoietic effects after treatment. Thirty-six patients treated from 2005 to 2015 were identified retroactively. The time course of treatment, including gestational age and number of IUT, and timing of delivery were reviewed. Fetal reticulocyte count and neonatal hemoglobin and reticulocyte counts were analyzed for each IUT. For each gestational week, reticulocyte count decreased by ∼8.6% (95% confidence interval [CI]: 5.3-12.0). In the neonatal period, there was significant correlation between hemoglobin at birth and number of transfusions (Spearman correlation 0.473, 95% CI: 0.113-0.715, P =0.01) as well as reticulocyte count at birth and number of transfusions (Spearman correlation: 0.393, 95% CI: 0.058-0.642, P =0.02). IUT appears to have a direct and measurable effect on fetal reticulocyte production which persists in neonates.

Transcriptome annotation reveals minimal immunogenetic diversity among Wyoming toads, Anaxyrus baxteri.

Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes.