Association between potentially inappropriate medications prescription and health-related quality of life among US older adults.

BACKGROUND: Potentially inappropriate medications (PIMs) are associated with worse health outcomes among older adults. Our objective was to examine the association between PIM prescription and health-related quality of life (HRQoL) among older adults in the United States using nationally representative data. METHODS: This was a retrospective study utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data. Community dwelling US adults aged 65 years or older were included. A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to define exposure to PIMs during the study period. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) were used to measure HRQoL. Survey-weighted linear regression models were constructed to investigate the association between PIM exposure and participants' PCS and MCS scores. Analyses were stratified across three age cohorts (65-74, 75-85, and ≥85 years). RESULTS: Unadjusted analysis showed poorer scores in the PIM exposed group for both PCS and MCS (all p < 0.001). PIM exposure was associated with poorer PCS scores across all age groups with those aged 65-74 years (adjusted regression coefficient = -1.60 [95% CI = -2.27, -0.93; p < 0.001]), those 75-84 years (adjusted regression coefficient: -1.49 [95% CI = -2.45, -0.53; p = 0.003]), and those 85 years and older (adjusted regression coefficient = -1.65 [95% CI = -3.03, -0.27; p = 0.02]). PIM exposure was also associated with poorer MCS scores in participants aged 65-74 years (adjusted regression coefficient = -0.69 [95% CI = -1.16, -0.22; p = 0.004]) and 85 years and older (adjusted regression coefficient = -2.01 [95% CI = -3.25, -0.78; p = 0.002]). CONCLUSIONS: Our results suggest that patients' exposure to PIMs is associated with poorer HRQoL. Further work is needed to assess whether interventions to deprescribe PIMs may help to improve patients' HRQoL.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation.

Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathological factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer(BC) chemotherapy response remains poorly understood. This study examines the variance in the gut microbiome(GM) of BC patients compared to healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease. Our study reveals distinct clustering, effectively separating the BC and healthy cohorts. However, no significant differences were observed between chemotherapy responders and non-responders within community subgroups. Machine Learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs AUC 0.50), although no single microbial species emerged as a fully reliable biomarker. The evaluation of short-chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, p = 0.017) and Clostridia (rs = 0.52, p = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, p=0.02) and Enterobacteriaceae (rs = 0.52, p < 0.03) correlated with increased fecal propionic acid. In conclusion, our study constitutes the first large-scale, multi-center assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa.

Attention capture by own name decreases with speech compression.

Auditory stimuli that are relevant to a listener have the potential to capture focal attention even when unattended, the listener's own name being a particularly effective stimulus. We report two experiments to test the attention-capturing potential of the listener's own name in normal speech and time-compressed speech. In Experiment 1, 39 participants were tested with a visual word categorization task with uncompressed spoken names as background auditory distractors. Participants' word categorization performance was slower when hearing their own name rather than other names, and in a final test, they were faster at detecting their own name than other names. Experiment 2 used the same task paradigm, but the auditory distractors were time-compressed names. Three compression levels were tested with 25 participants in each condition. Participants' word categorization performance was again slower when hearing their own name than when hearing other names; the slowing was strongest with slight compression and weakest with intense compression. Personally relevant time-compressed speech has the potential to capture attention, but the degree of capture depends on the level of compression. Attention capture by time-compressed speech has practical significance and provides partial evidence for the duplex-mechanism account of auditory distraction.

Evidence of reassortment of avian influenza A (H2) viruses in Brazilian shorebirds.

Influenza A viruses of the H2 subtype represent a zoonotic and pandemic threat to humans due to a lack of widespread specific immunity. Although A(H2) viruses that circulate in wild bird reservoirs are distinct from the 1957 pandemic A(H2N2) viruses, there is concern that they could impact animal and public health. There is limited information on AIVs in Latin America, and next to nothing about H2 subtypes in Brazil. In the present study, we report the occurrence and genomic sequences of two influenza A viruses isolated from wild-caught white-rumped sandpipers (Calidris fuscicollis). One virus, identified as A(H2N1), was isolated from a bird captured in Restinga de Jurubatiba National Park (PNRJ, Rio de Janeiro), while the other, identified as A(H2N2), was isolated from a bird captured in Lagoa do Peixe National Park (PNLP, Rio Grande do Sul). DNA sequencing and phylogenetic analysis of the obtained sequences revealed that each virus belonged to distinct subtypes. Furthermore, the phylogenetic analysis indicated that the genomic sequence of the A(H2N1) virus isolated from PNRJ was most closely related to other A(H2N1) viruses isolated from North American birds. On the other hand, the A(H2N2) virus genome recovered from the PNLP-captured bird exhibited a more diverse origin, with some sequences closely related to viruses from Iceland and North America, and others showing similarity to virus sequences recovered from birds in South America. Viral genes of diverse origins were identified in one of the viruses, indicating local reassortment. This suggests that the extreme South of Brazil may serve as an environment conducive to reassortment between avian influenza virus lineages from North and South America, potentially contributing to an increase in overall viral diversity.

Insights into wheat-starch biosynthesis from two-dimensional macromolecular structure.

Starch structure is often characterized by the chain-length distribution (CLD) of the linear molecules formed by breaking each branch-point. More information can be obtained by expanding into a second dimension: in the present case, the total undebranched-molecule size. This enables answers to questions unobtainable by considering only one variable. The questions considered here are: (i) are the events independent which control total size and CLD, and (ii) do ultra-long amylopectin (AP) chains exist (these chains cannot be distinguished from amylose chains using simple size separation). This was applied here to characterize the structures of one normal (RS01) wheat and two high-amylose (AM) mutant wheats (an SBEIIa knockout and an SBEIIa and SBEIIb knockout). Absolute ethanol was used to precipitate collected fractions, then size-exclusion chromatography for total molecular size and for the size of branches. The SBEIIa and SBEIIb mutations significantly increased AM and IC contents and chain length. The 2D plots indicated the presence of small but significant amounts of long-chain amylopectin, and the asymmetry of these plots shows that the corresponding mechanisms share some causal effects. These results could be used to develop plants producing improved starches, because different ranges of the chain-length distribution contribute independently to functional properties.

Ecological and anthropogenic drivers of waterfowl productivity are synchronous across species, space, and time.

Knowledge of interspecific and spatiotemporal variation in demography-environment relationships is key for understanding the population dynamics of sympatric species and developing multispecies conservation strategies. We used hierarchical random-effects models to examine interspecific and spatial variation in annual productivity in six migratory ducks (i.e., American wigeon [Mareca americana], blue-winged teal [Spatula discors], gadwall [Mareca strepera], green-winged teal [Anas crecca], mallard [Anas platyrhynchos] and northern pintail [Anas acuta]) across six distinct ecostrata in the Prairie Pothole Region of North America. We tested whether breeding habitat conditions (seasonal pond counts, agricultural intensification, and grassland acreage) or cross-seasonal effects (indexed by flooded rice acreage in primary wintering areas) better explained variation in the proportion of juveniles captured during late summer banding. The proportion of juveniles (i.e., productivity) was highly variable within species and ecostrata throughout 1961-2019 and generally declined through time in blue-winged teal, gadwall, mallard, pintail, and wigeon, but there was no support for a trend in green-winged teal. Productivity in Canadian ecostrata declined with increasing agricultural intensification and increased with increasing pond counts. We also found a strong cross-seasonal effect, whereby more flooded rice hectares during winter resulted in higher subsequent productivity. Our results suggest highly consistent environmental and anthropogenic effects on waterfowl productivity across species and space. Our study advances our understanding of current year and cross-seasonal effects on duck productivity across a suite of species and at finer spatial scales, which could help managers better target working-lands conservation programs on both breeding and wintering areas. We encourage other researchers to evaluate environmental drivers of population dynamics among species in a single modeling framework for a deeper understanding of whether conservation plans should be generalized or customized given limited financial resources.

Photochemical Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Evaluation in Ex Vivo Human Tissue.

PURPOSE: Experimental investigation in human eyelids to confirm that exposing excised tarsal plates to ultraviolet-A radiation can induce a stiffening effect through the riboflavin-photosensitized crosslinking of tarsal collagen. METHODS: Thirteen tarsal plates excised from nonfrozen human cadavers were irradiated with ultraviolet-A rays (365 nm wavelength) at an irradiance of 75 mW/cm2 for 3 minutes, equivalent to a radiation fluence of 13.5 J/cm2, in the presence of a riboflavin derivative as a photosensitizer. The tensile stress (strength) and Young's modulus (stiffness) of both nonirradiated and irradiated specimens were measured with the BioTester 5000 in the uniaxial mode at a strain of 10% and analyzed statistically. Individual specimens excised from 2 cadavers were also examined by routine histopathologic protocols to assess the effect of radiation on the Meibomian glands and collagen organization. RESULTS: The irradiation enhanced both stiffness and strength of the human tarsal specimens, the difference between the test samples and controls being statistically significant (p < 0.0002 for n = 13). Histology indicated no damage to tarsal connective tissue or to Meibomian glands, and revealed a more compact packing of the collagen network located around the glands, which may be beneficial. The existence of collagen compaction was also supported by the reduction of samples' thickness after irradiation (p = 0.0645). CONCLUSIONS: The irradiation of tarsal tissue with ultraviolet-A light of tarsus appears to be a safe and effective method for reducing eyelid laxity in human patients.

Anion-Dependent Strength Scale of Interactions in Ionic Liquids from X-ray Photoelectron Spectroscopy, Ab Initio Molecular Dynamics, and Density Functional Theory.

Using a combination of experiments and calculations, we have gained new insights into the nature of anion-cation interactions in ionic liquids (ILs). An X-ray photoelectron spectroscopy (XPS)-derived anion-dependent electrostatic interaction strength scale, determined using XPS core-level binding energies for IL cations, is presented here for 39 different anions, with at least 18 new anions included. Linear correlations of experimental XPS core-level binding energies for IL cations with (a) calculated core binding energies (ab initio molecular dynamics (AIMD) simulations were used to generate high-quality model IL structures followed by single-point density functional theory (DFT) to obtain calculated core binding energies), (b) experimental XPS core-level binding energies for IL anions, and (c) other anion-dependent interaction strength scales led to three main conclusions. First, the effect of different anions on the cation can be related to ground-state interactions. Second, the variations of anion-dependent interactions with the identity of the anion are best rationalized in terms of electrostatic interactions and not occupied valence state/unoccupied valence state interactions or polarizability-driven interactions. Therefore, the XPS-derived anion-dependent interaction strength scale can be explained using a simple electrostatic model based on electrostatic site potentials. Third, anion-probe interactions, irrespective of the identity of the probe, are primarily electrostatic, meaning that our electrostatic interaction strength scale captures some inherent, intrinsic property of anions independent of the probe used to measure the interaction strength scale.

Anionic Effects on Concentrated Aqueous Lithium Ion Dynamics.

The dynamics, orientational anisotropy, diffusivity, viscosity, and density were measured for concentrated lithium salt solutions, including lithium chloride (LiCl), lithium bromide (LiBr), lithium nitrite (LiNO2), and lithium nitrate (LiNO3), with methyl thiocyanate as an infrared vibrational probe molecule, using two-dimensional infrared spectroscopy (2D IR), nuclear magnetic resonance (NMR) spectroscopy, and viscometry. The 2D IR, NMR, and viscosity results show that LiNO2 exhibits longer correlation times, lower diffusivity, and nearly 4 times greater viscosity compared to those of the other lithium salt solutions of the same concentration, suggesting that nitrite anions may strongly facilitate structure formation via strengthening water-ion network interactions, directly impacting bulk solution properties at sufficiently high concentrations. Additionally, the LiNO2 and LiNO3 solutions show significantly weakened chemical interactions between the lithium cations and the methyl thiocyanate when compared with those of the lithium halide salts.

Structural characterization of E22G Aß1-42 fibrils via1H detected MAS NMR.

Amyloid fibrils have been implicated in the pathogenesis of several neurodegenerative diseases, the most prevalent example being Alzheimer's disease (AD). Despite the prevalence of AD, relatively little is known about the structure of the associated amyloid fibrils. This has motivated our studies of fibril structures, extended here to the familial Arctic mutant of Aß1-42, E22G-Aß1-42. We found E22G-AßM0,1-42 is toxic to Escherichia coli, thus we expressed E22G-Aß1-42 fused to the self-cleavable tag NPro in the form of its EDDIE mutant. Since the high surface activity of E22G-Aß1-42 makes it difficult to obtain more than sparse quantities of fibrils, we employed 1H detected magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments to characterize the protein. The 1H detected 13C-13C methods were first validated by application to fully protonated amyloidogenic nanocrystals of GNNQQNY, and then applied to fibrils of the Arctic mutant of Aß, E22G-Aß1-42. The MAS NMR spectra indicate that the biosynthetic samples of E22G-Aß1-42 fibrils comprise a single conformation with 13C chemical shifts extracted from hCH, hNH, and hCCH spectra that are very similar to those of wild type Aß1-42 fibrils. These results suggest that E22G-Aß1-42 fibrils have a structure similar to that of wild type Aß1-42.

Interfacially enhanced superconductivity in Fe(Te,Se)/Bi4Te3 heterostructures.

Realizing topological superconductivity by integrating high-transition-temperature (TC) superconductors with topological insulators can open new paths for quantum computing applications. Here, we report a new approach for increasing the superconducting transition temperature ( T C o n s e t ) $( {T_C^{onset}} )$ by interfacing the unconventional superconductor Fe(Te,Se) with the topological insulator Bi-Te system in the low-Se doping regime, near where superconductivity vanishes in the bulk. The critical finding is that the T C o n s e t $T_C^{onset}$ of Fe(Te,Se) increases from nominally non-superconducting to as high as 12.5 K when Bi2Te3 is replaced with the topological phase Bi4Te3. Interfacing Fe(Te,Se) with Bi4Te3 is also found to be critical for stabilizing superconductivity in monolayer films where T C o n s e t $T_C^{onset}$ can be as high as 6 K. Measurements of the electronic and crystalline structure of the Bi4Te3 layer reveal that a large electron transfer, epitaxial strain, and novel chemical reduction processes are critical factors for the enhancement of superconductivity. This novel route for enhancing TC in an important epitaxial system provides new insight on the nature of interfacial superconductivity and a platform to identify and utilize new electronic phases. This article is protected by copyright. All rights reserved.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Development of Fused Deposition Modeling of Multiple Materials (FD3M) Through Dynamic Coaxial Extrusion.

Multimaterial additive manufacturing is expanding the design space realizable with 3D printing, yet is largely constrained to sequential deposition of each individual material. The ability to coextrude two materials and change the ratio of materials while printing would enable custom-tailored polymer composites. Here, the evolution of a dynamic material coextrusion process for additive manufacturing capable of printing any ratio between and including two neat input materials is described across 3 hot-end generations and 14 implemented design iterations. The designs evolved with increased understanding of manufacturing constraints associated with the additive manufacturing of metal components with internal flow bore diameters on the order of 2 mm and typical bore length around 50 mm. The second generation overcame this issue by partitioning the design into two pieces to locate the flow channel geometry at the interface between the components so that the details could be easily printed on the components' external surfaces. The third concept generation then focused on minimizing flow channel volume to reduce the average length when transitioning between materials by 92%. The third-generation design was also used to investigate the improvements in dimensional stability during annealing of acrylonitrile butadiene styrene (ABS) made possible by coextruding ABS with a polycarbonate (PC) core. The standard deviation of part shrinkage after annealing was 7.08% for the neat ABS but reduced to 0.24% for the coextruded ABS/PC components.

Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE.

BACKGROUND: In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI). METHODS: This was a secondary analysis of the PACIFIC-STROKE trial. Patients with mild-to-moderate acute noncardioembolic ischemic stroke were randomly assigned to asundexian or placebo plus guideline-based antiplatelet therapy. Brain MRIs were required at baseline (≤120 hours after stroke onset) and at 26 weeks or end-of-study. HT was defined using the Heidelberg classification and classified as early HT (identified on baseline MRI) or late HT (new HT by 26 weeks) based on iron-sensitive sequences. Multivariable logistic regression models were used to test factors that are associated with early HT and late HT, respectively. RESULTS: Of 1745 patients with adequate baseline brain MRI (mean age, 67 years; mean National Institutes of Health Stroke Scale score, 2.8), early HT at baseline was detected in 497 (28.4%). Most were hemorrhagic infarctions (hemorrhagic infarction type 1: 15.2%; HI2: 12.7%) while a few were parenchymal hematomas (parenchymal hematoma type 1: 0.4%; parenchymal hematoma type 2: 0.2%). Early HT was more frequent with longer symptom onset-to-MRI interval. Male sex, diabetes, higher National Institutes of Health Stroke Scale large (>15 mm) infarct size, cortical involvement by infarct, higher number of acute infarcts, presence of chronic brain infarct, cerebral microbleed, and chronic cortical superficial siderosis were independently associated with early HT in the multivariable logistic regression model. Of 1507 with follow-up MRI, HT was seen in 642 (42.6%) overall, including 361 patients (23.9%) with late HT (new HT: 306; increased grade of baseline HT: 55). Higher National Institutes of Health Stroke Scale, large infarct size, cortical involvement of infarct, and higher number of acute infarcts predicted late HT. CONCLUSIONS: About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes.

Strength Training Frequency and Athletic Performance in High School Girls Basketball Players.

This study investigated the effects of a six-week strength training intervention on the physical fitness of female high school athletes, with a focus on training frequency. Twenty-three female high school basketball athletes were recruited and split into two groups: one group participated in strength training once per week (S1), while the other participated in two training sessions per week (S2). The groups were not random as training sessions were voluntary, and some participants were only able to train once per week. Participants were tested before and after the intervention, and the data included: age, body height, body mass, body fat percentage, grip strength, leg/back dynamometer (LBD) strength, a seated medicine ball throw (MBT), a vertical jump (VJ), 505 tests from each foot, 0-5, 0-10, and 0-20 sprint times, and multistage fitness test shuttles. Data were analyzed by a two (time) x two (group) repeated measures analysis of variance (ANOVA; p < 0.05). When significant F ratios were detected in any ANOVA calculations, post hoc pairwise comparisons were conducted using the Bonferroni adjustment procedure. There were significant main effects for time that indicated the following: increased body height, body mass, grip strength, LBD strength, MBT distance, and VJ height, faster 505 times, and slower 0-5 and 0-10 m sprint times (p ≤ 0.021). There were no significant time by group ANOVAs or between-group main effects. These performance changes occurred irrespective of training frequency. High school girls who participate in at least one strength training session per week can improve their strength (grip, LBD), power (MBT, VJ), and change-of-direction speed (505).

Preclinical validation of an Escherichia coli O-antigen glycoconjugate for the prevention of serotype O1 invasive disease.

A US collection of invasive Escherichia coli serotype O1 bloodstream infection (BSI) isolates were assessed for genotypic and phenotypic diversity as the basis for designing a broadly protective O-antigen vaccine. Eighty percent of the BSI isolate serotype O1 strains were genotypically ST95 O1:K1:H7. The carbohydrate repeat unit structure of the O1a subtype was conserved in the three strains tested representing core genome multi-locus sequence types (MLST) sequence types ST95, ST38, and ST59. A long-chain O1a CRM197 lattice glycoconjugate antigen was generated using oxidized polysaccharide and reductive amination chemistry. Two ST95 strains were investigated for use in opsonophagocytic assays (OPA) with immune sera from vaccinated animals and in murine lethal challenge models. Both strains were susceptible to OPA killing with O1a glycoconjugate post-immune sera. One of these, a neonatal sepsis strain, was found to be highly lethal in the murine challenge model for which virulence was shown to be dependent on the presence of the K1 capsule. Mice immunized with the O1a glycoconjugate were protected from challenges with this strain or a second, genotypically related, and similarly virulent neonatal isolate. This long-chain O1a CRM197 lattice glycoconjugate shows promise as a component of a multi-valent vaccine to prevent invasive E. coli infections. IMPORTANCE: The Escherichia coli serotype O1 O-antigen serogroup is a common cause of invasive bloodstream infections (BSI) in populations at risk such as newborns and the elderly. Sequencing of US BSI isolates and structural analysis of O polysaccharide antigens purified from strains that are representative of genotypic sub-groups confirmed the relevance of the O1a subtype as a vaccine antigen. O polysaccharide was purified from a strain engineered to produce long-chain O1a O-antigen and was chemically conjugated to CRM197 carrier protein. The resulting glycoconjugate elicited functional antibodies and was protective in mice against lethal challenges with virulent K1-encapsulated O1a isolates.

Anesthesia-induced Lymphatic Dysfunction.

General anesthetics adversely alters the distribution of infused fluid between the plasma compartment and the extravascular space. This maldistribution occurs largely from the effects of anesthetic agents on lymphatic pumping, which can be demonstrated by macroscopic fluid kinetics studies in awake versus anesthetized patients. The magnitude of this effect can be appreciated as follows: a 30% reduction in lymph flow may result in a fivefold increase of fluid-induced volume expansion of the interstitial space relative to plasma volume. Anesthesia-induced lymphatic dysfunction is a key factor why anesthetized patients require greater than expected fluid administration than can be accounted for by blood loss, urine output, and insensible losses. Anesthesia also blunts the transvascular refill response to bleeding, an important compensatory mechanism during hemorrhagic hypovolemia, in part through lymphatic inhibition. Last, this study addresses how catecholamines and hypertonic and hyperoncotic fluids may mobilize interstitial fluid to mitigate anesthesia-induced lymphatic dysfunction.

Title: Cross-sectional associations between nutrient intake and tooth decay in older Australian men: The Concord Health and Ageing in Men Project.

Poor nutrition is a risk factor for dental decay in younger people. However, except for sugar it is unclear if this is true in older age groups. The aim of this study was to analyze the possible associations between overall dietary intake of nutrients and diet quality and presence of dental decay in community dwelling older men. A cross-sectional analysis of a longitudinal study with a standardized validated diet history assessment and comprehensive oral health examination in 520 community dwelling men (mean age: 84 years) participating in the Concord Health and Ageing in Men Project. Nutrient Reference Values (NRVs) were used to determine if individual micronutrients and macronutrients were meeting recommendations. Acceptable Macronutrient Distribution Ranges (AMDR) were attained for fat and carbohydrate intakes and were incorporated into a dichotomous variable to determine if the participants were consuming a high fat and low carbohydrate diet. Diagnosis of coronal caries was based on visual criteria and inspection and was completed on each of the five coronal surfaces. Root surface caries was textual changes across four root surfaces. This diagnosis was used to categorize participants by presence and severity of coronal and root caries. Adjusted logistic regression showed not meeting the recommended intakes for thiamin (odds ratio (OR): 2.32 95% confidence interval (CI) 1.15 - 4.67), and zinc (OR: 3.33, 95% CI 1.71 - 6.48) were associated with presence of severe root decay. Adjusted analysis also showed that participants who were outside the recommended AMDR for fat (OR: 0.61, 95% CI 0.38 - 0.98), and those who consumed a high fat and low carbohydrate diet (OR: 0.56, 95% CI 0.35 - 0.91) were less likely to have coronal tooth decay. Our study shows associations between micronutrients and macronutrients and coronal and root surface decay. Although this study cannot prescribe causality or be generalized to all older adults, diet has a possible association with dental decay in older men.

The Forgotten Virus, Hepatitis D: A Review of Epidemiology, Diagnosis, and Current Treatment Strategies.

Hepatitis D virus (HDV) is an RNA subvirus that infects patients with co-existing hepatitis B virus (HBV) infections. HDV burden is estimated to be approximately 15-20 million people worldwide. Despite HDV severity, screening for HDV remains inadequate. HDV screening would benefit from a revamped approach that automatically reflexes testing when individuals are diagnosed with HBV if HBsAg-positive, to total anti-HDV, and then to quantitative HDV-RNA polymerase chain reaction (PCR) rather than only testing those at high risk sequentially. There are no current treatments in the United States that are Food and Drug Administration (FDA)-approved for the treatment of HDV; however, bulevirtide (BLV) is approved in the European Union conditionally and is under review with the United States FDA. Current treatment strategies in many countries are centered on the use of pegylated-interferon-alfa-2a (PEG-IFNa-2a). There are other therapies in development globally that have shown promise, including BLV, pegylated-interferon-lambda (PEG-IFN-lambda), and lonafarnib (LNF). LNF has shown substantial response in the LOWR trials. BLV is a well-tolerated drug, but it is not finite therapy and has shown significant on-treatment responses in the MYR clinical trials, and the FDA cited concerns with the manufacturing and patient preparation of the drug that have delayed approval. The PDUFA date for BLV in the United States is mid-2024. Current studies with both BLV and LNF are limited in providing sustained virological response (SVR); future trials will need to demonstrate more substantial SVR with possible triple combination trials as options.