Gender differences in diet quality and the association between diet quality and BMI: an analysis in young Australian adults who completed the Healthy Eating Quiz.

BACKGROUND: Many young adults report poor diet quality. However, research evaluating whether young adult males and females differ in diet quality is limited. Additionally, although diet quality has a known inverse association with body mass index (BMI), it is unclear whether this association is observed in young adults and whether it varies by gender. The present study aimed to evaluate gender differences in diet quality in young adults, as well as the associations between diet quality and BMI. METHODS: Data collected via the Healthy Eating Quiz (HEQ) in respondents aged 18-35 years between July 2019 and December 2021 were analysed, including demographics, and diet quality calculated using the Australian Recommended Food Score (ARFS). Differences in characteristics were analysed using a two-sample t-test, chi-squared and one-way analysis of covariance. Linear regressions were performed to estimate associations between diet quality and BMI. An interaction term was included in the model to test differences between genders. RESULTS: The respondents (n = 28,969) were predominantly female (70.8%) with a mean ± SD age of 25.9 ± 5.0 years and BMI of 24.6 ± 5.2 kg/m2. The mean ± SD ARFS was significantly different between females and males (33.1 ± 8.6 vs. 31.4 ± 9.3 points out of 70; p < 0.001). Diet quality had a small, significant inverse association with BMI in both genders. The interaction effect between diet quality score and gender in predicting BMI was significant (p < 0.001), suggesting the impact of diet quality on BMI varies by gender, with lower diet quality more strongly associated with higher BMI in females compared to males. CONCLUSION: Interventions that target young adults are needed to improve diet quality and its potential contribution to BMI status. As a result of the small observed effect sizes, caution should be applied in interpreting these findings.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

BACKGROUND: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using 99mTc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. METHODS AND RESULTS: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The 99mTc-duramycin+ areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc-duramycin+ tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc-duramycin+-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, P<0.05; circumferential strain -52.9%, P<0.05). CONCLUSIONS: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.

Leveraging Routinely Collected Program Data to Inform Extrapolated Size Estimates for Key Populations in Namibia: Small Area Estimation Study.

BACKGROUND: Estimating the size of key populations, including female sex workers (FSW) and men who have sex with men (MSM), can inform planning and resource allocation for HIV programs at local and national levels. In geographic areas where direct population size estimates (PSEs) for key populations have not been collected, small area estimation (SAE) can help fill in gaps using supplemental data sources known as auxiliary data. However, routinely collected program data have not historically been used as auxiliary data to generate subnational estimates for key populations, including in Namibia. OBJECTIVE: To systematically generate regional size estimates for FSW and MSM in Namibia, we used a consensus-informed estimation approach with local stakeholders that included the integration of routinely collected HIV program data provided by key populations' HIV service providers. METHODS: We used quarterly program data reported by key population implementing partners, including counts of the number of individuals accessing HIV services over time, to weight existing PSEs collected through bio-behavioral surveys using a Bayesian triangulation approach. SAEs were generated through simple imputation, stratified imputation, and multivariable Poisson regression models. We selected final estimates using an iterative qualitative ranking process with local key population implementing partners. RESULTS: Extrapolated national estimates for FSW ranged from 4777 to 13,148 across Namibia, comprising 1.5% to 3.6% of female individuals aged between 15 and 49 years. For MSM, estimates ranged from 4611 to 10,171, comprising 0.7% to 1.5% of male individuals aged between 15 and 49 years. After the inclusion of program data as priors, the estimated proportion of FSW derived from simple imputation increased from 1.9% to 2.8%, and the proportion of MSM decreased from 1.5% to 0.75%. When stratified imputation was implemented using HIV prevalence to inform strata, the inclusion of program data increased the proportion of FSW from 2.6% to 4.0% in regions with high prevalence and decreased the proportion from 1.4% to 1.2% in regions with low prevalence. When population density was used to inform strata, the inclusion of program data also increased the proportion of FSW in high-density regions (from 1.1% to 3.4%) and decreased the proportion of MSM in all regions. CONCLUSIONS: Using SAE approaches, we combined epidemiologic and program data to generate subnational size estimates for key populations in Namibia. Overall, estimates were highly sensitive to the inclusion of program data. Program data represent a supplemental source of information that can be used to align PSEs with real-world HIV programs, particularly in regions where population-based data collection methods are challenging to implement. Future work is needed to determine how best to include and validate program data in target settings and in key population size estimation studies, ultimately bridging research with practice to support a more comprehensive HIV response.

Prostate-Specific Antigen Screening in Smokers: A Comprehensive Analysis Using a National Behavioral Survey.

INTRODUCTION: Cigarette smoking is associated with higher-risk prostate cancer at the time of diagnosis and increased overall and prostate cancer‒specific mortality. Previous studies indicate smokers are less likely to undergo PSA screening. Herein we investigate the association between smoking and PSA screening using a nationally representative US survey. We hypothesize that smokers are less likely to undergo guideline-concordant PSA screening. METHODS: We performed a cross-sectional analysis of men aged 55 to 69 who responded to the cigarette smoking and PSA screening questions of the 2018 Behavioral Risk Factor Surveillance System survey. Adjusted prevalence and adjusted risk differences were calculated using complex weighted multivariable Poisson regression modeling. RESULTS: We identified 58,996 individuals who qualified for analysis. PSA screening prevalence was 39% (95% CI: 39%-40%) nationally, 42% (95% CI: 41%-44%) for never smokers, 42% (95% CI: 39%-40%) for former smokers, and 27% (95% CI: 25%-29%) for current smokers, including 27% (95% CI: 24%-29%) for daily smokers and 29% (95% CI: 24%-33%) for nondaily smokers. Compared to never smokers, the adjusted relative risk for undergoing PSA screening was 0.81 for current smokers (95% CI: 0.75-0.88, P < .01) and 0.99 for former smokers (95% CI: 0.94-1.03, P = .53). CONCLUSIONS: Current smokers are less likely to undergo recommended PSA screening, but former smokers are screened at similar rates as never smokers. As delays in diagnosis may substantially contribute to worse prostate cancer outcomes, targeted interventions to increase screening in this population may yield significant effects.

Iron-Mediated Dialkylation of Alkenylarenes with Benzyl Bromides.

We disclose a method for the dibenzylation of alkenylarenes with benzyl bromides using iron powder. This reaction generates branched alkyl scaffolds adorned with functionalized aryl rings through the formation of two new C(sp3)-C(sp3) bonds at the vicinal carbons of alkenes. This protocol tolerates electron-rich, electron-neutral, and electron-poor benzyl bromides and alkenylarenes. Mechanistic studies suggest the formation of benzylic radical intermediates as a result of single-electron transfer from the iron, which is intercepted by alkenylarenes.

Combined Transnasal, Transoral Excision of Odontogenic Cysts Offers Reduced Recurrence Rates and Favorable Sinonasal Outcomes.

Odontogenic cysts impact the adjacent dentition and maxillary sinus. A combined transnasal, transoral approach for removal offers reduced recurrence rates and favorable sinonasal outcomes compared with historic transoral-only approaches.

Metabolic regulation of longevity and immune response in Caenorhabditis elegans by ingestion of Lacticaseibacillus rhamnosus IDCC 3201 using multi-omics analysis.

Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotics properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.

Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps. We identified a facile synthetic protocol via a highly enantioselective one-step process for epinephrine and a two-step process for norepinephrine starting from unprotected α-ketoamines 1b and 1a, respectively. This newly developed enantioselective ruthenium-catalyzed asymmetric transfer hydrogenation was extended to the synthesis of many 1,2-amino alcohol-containing drug molecules such as phenylephrine, denopamine, norbudrine, and levisoprenaline, with enantioselectivities of >99% ee and high isolated yields.

Transcutaneous electrical nerve stimulation for the treatment of acute postoperative pain following spine surgery: a scoping review.

OBJECTIVE: Given the ubiquity and severity of postoperative pain following spine surgery, developing adequate pain management modalities is critical. Transcutaneous electrical nerve stimulation (TENS) is a promising noninvasive modality that is well studied for managing postoperative pain following a variety of surgeries, but data on using TENS for pain management in the acute postoperative period of spine surgery are limited. Therefore, this review aimed to recapitulate the existing evidence for the use of TENS in postoperative pain management for spine surgery and explore the potential of this modality moving forward. METHODS: A scoping review was conducted according to 2020 PRISMA guidelines. Two independently operating reviewers then conducted a systematic search of PubMed, Embase, and Scopus databases to identify studies that reported the use of TENS for the treatment of acute postoperative pain following spine surgery. The following data were abstracted from included studies: study type, sample size, demographics, surgery details, comparison group, assessment parameters, timing of postoperative assessment, TENS technical characteristics, relevant findings, length of hospital stay, complications with TENS, and notable limitations. RESULTS: Nine hundred thirty-two publications were screened, resulting in 6 studies included in this review, all of which were prospective clinical trials. The publication dates ranged from 1980 to 2011. Spine surgery types varied; the most common was posterior lumbar interbody fusion. No studies evaluated pain control in cervical- or thoracic-only surgeries. All 6 studies evaluated the level of postoperative pain directly. Five of the 6 studies that directly examined postoperative pain reported lower levels of pharmacological analgesia usage in the TENS groups compared with controls, with 4 of these studies reporting this difference as statistically significant. Length of hospital stay was evaluated in 2 studies, both of which reported decreases in mean length of stay, but these differences were not significant. Notably, every study reported distinct TENS administration parameters while also reporting similar results. CONCLUSIONS: This review concludes that TENS is effective at reducing postoperative pain in spine surgery. Further investigation is needed regarding the optimal settings for TENS administration, as well as efficacy in the thoracic and cervical spine.

Comparison between Two Adaptive Optics Methods for Imaging of Individual Retinal Pigmented Epithelial Cells.

The Retinal Pigment Epithelium (RPE) plays a prominent role in diseases such as age-related macular degeneration, but imaging individual RPE cells is challenging due to their high absorption and low autofluorescence emission. The RPE lies beneath the highly reflective photoreceptor layer (PR) and contains absorptive pigments, preventing direct backscattered light detection when the PR layer is intact. Here, we used near-infrared autofluorescence adaptive optics scanning laser ophthalmoscopy (NIRAF AOSLO) and transscleral flood imaging (TFI) in the same healthy eyes to cross-validate these approaches. Both methods revealed a consistent RPE mosaic pattern and appeared to reflect a distribution of fluorophores consistent with findings from histological studies. Interestingly, even in apparently healthy RPE, we observed dynamic changes over months, suggesting ongoing cellular activity or alterations in fluorophore distribution. These findings emphasize the value of NIRAF AOSLO and TFI in understanding RPE morphology and dynamics.

Prospective assessment of the impact of intraoperative diuretics in kidney transplant recipient surgery.

BACKGROUND: The use of intraoperative diuretics, such as furosemide or mannitol, during kidney transplantation has been suggested to reduce the rate of delayed graft function (DGF). The evidence base for this is sparse, however, and there is substantial variation in practice. We sought to evaluate whether the use of intraoperative diuretics during kidney transplantation translated into a reduction in DGF. METHODS: We conducted a cohort study evaluating the use of furosemide or mannitol given intraoperatively before kidney reperfusion compared with control (no diuretic). Adult patients receiving a kidney transplant for end-stage renal disease were allocated to receive furosemide, mannitol, or no diuretic. The primary outcome was DGF; secondary outcomes were graft function at 30 days and perioperative changes in potassium levels. Descriptive and comparative statistics were used where appropriate. RESULTS: A total of 162 patients who received a kidney transplant from a deceased donor (either donation after neurologic determination of death or donation after circulatory death) were included over a 2-year period, with no significant between-group differences. There was no significant difference in DGF rates between the furosemide, mannitol, and control groups. When the furosemide and mannitol groups were pooled (any diuretic use) and compared with the control group, however, there was a significant improvement in the odds that patients would be free of DGF (odds ratio 2.10, 95% confidence interval 1.06-4.16, 26% v. 44%, p = 0.03). There were no significant differences noted in any secondary outcomes. CONCLUSION: This study suggests the use of an intraoperative diuretic (furosemide or mannitol) may result in a reduction in DGF in patients undergoing kidney transplantation. Further study in the form of a randomized controlled trial is warranted.

FDA Approval Summary: Enfortumab Vedotin Plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma.

On April 3, 2023, the FDA granted accelerated approval to enfortumab vedotin-ejfv (EV) plus pembrolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Substantial evidence of effectiveness was obtained from EV-103/KEYNOTE-869 (NCT03288545), a multi-cohort study. Across cohorts, a total of 121 patients received EV 1.25 mg/kg (maximum of 125 mg) intravenously on days 1 and 8 of a 21-day cycle plus pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) determined by blinded independent central review using RECIST v1.1. The confirmed ORR in 121 patients was 68% (95% CI: 59, 76), including 12% with complete responses. The median DoR for the 82 responders was 22 months (range: 1+ to 46+). The safety profile of the combination comprised adverse reactions expected to occur with the corresponding monotherapies, but with overall increased frequency of adverse reactions, including skin toxicity, pneumonitis, and peripheral neuropathy. The article summarizes the data and the FDA thought process supporting accelerated approval of EV + pembrolizumab, as well as additional exploratory analyses conducted by the FDA.

Predictors of non-primary auditory and vestibular symptom persistence following surgical repair of superior canal dehiscence syndrome.

Objective: Patients with superior canal dehiscence syndrome (SCDS) can present with a plethora of auditory and/or vestibular symptoms associated with a bony defect of the superior semicircular canal. While surgical repair is a reasonable option for patients with significant localizing symptoms, the degree of clinical improvement will vary among patients and poses challenges in outcome prediction. This study aims to assess the relationship between preoperative and postoperative symptoms and identify predictors of symptom persistence following repair. Study design: Retrospective chart review. Setting: Tertiary neurotology single-institution care center. Main outcome measures: The primary outcome was to determine the proportion of resolved and persistent primary (most bothersome) and non-primary audiologic and vestibular symptoms following SCD repair. Secondary outcomes included comparison of patient, operative and radiologic characteristics between patients with resolved vs. persistent symptoms. Standardized patient questionnaires including 11 auditory and 8 vestibular symptoms were administered to patients at their preoperative and follow-up visits. Patient pre- vs. postoperative survey results, demographic and clinical characteristics, operative characteristics, audiometric data and cervical vestibular evoked myogenic potential (cVEMP) thresholds were compared via univariate χ2 and multivariate binary logistic regression analyses between those patients reporting full postoperative resolution of symptoms and persistence of one or more symptoms. Radiologic computed tomography (CT) measurements of superior canal dehiscence (SCD) defect size, location, and laterality were also compared between these two groups. Results: Of 126 patients (132 ears) included in our study, 119 patients (90.2%) reported postoperative resolution (n = 82, 62.1%) or improvement (n = 37, 28.0%) of primary (most bothersome) symptoms, while 13 patients (9.8%) reported persistence of primary symptoms. The median (interquartile range) and range between surgery and questionnaire completion were 9 (4-28), 1-124 months, respectively. Analyzing all symptoms (primary and non-primary) 69 (52.3%) and 68 (51.1%) patients reported complete postoperative auditory and vestibular symptom resolution, respectively. The most likely persistent symptoms included imbalance (33/65/67, 50.8%), positional dizziness (7/20, 35.0%) and oscillopsia (44/15, 26.7%). Factors associated with persistent auditory symptoms included history of seizures (0% vs. 7.6%, p = 0.023), auditory chief complaint (50.0% vs. 70.5%), higher PTA (mean 19.6 vs. 25.1 dB, p = 0.043) and higher cervical vestibular evoked myogenic potential (cVEMP) thresholds at 1000 Hz (mean 66.5 vs. 71.4, p = 0.033). A migraine diagnosis (14.0% vs. 41.9% p < 0.010), bilateral radiologic SCD (17.5% vs. 38.1%, p = 0.034) and revision cases (0.0% vs. 14.0%, p = 0.002) were associated with persistent vestibular symptoms. Neither SCD defect size nor location were significantly associated with symptom persistence (P > 0.05). Conclusions: Surgical repair for SCDS offers meaningful reduction in the majority of auditory and vestibular symptoms. However, the persistence of certain, mostly non-primary, symptoms and the identification of potential associated factors including migraines, PTA thresholds, cVEMP threshold, bilateral SCD, and revision cases emphasize the importance of individualized patient counseling and management strategies.

Highly multiplexed design of an allosteric transcription factor to sense novel ligands.

Allosteric transcription factors (aTF), widely used as biosensors, have proven challenging to design for detecting novel molecules because mutation of ligand-binding residues often disrupts allostery. We developed Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screened a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures - four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone - as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identified novel biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design showed shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we developed cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid, scalable design of new biosensors, overcoming constraints of natural biosensors.

Alcohol consumption and dependence risk among male and female Veterans: Trajectories and predictors.

BACKGROUND: With few exceptions, previously conducted research on hazardous drinking among Veterans has employed samples in which the majority of participants identify as male. In addition, past studies have solely focused on alcohol consumption, rather than associated risk for dependence. In this study, we expanded upon the extant literature by investigating sex differences in trajectories and predictors of change in alcohol consumption and dependence risk among post-9/11 Veterans. METHODS: A national sample of 1649 Veterans (50.0% female) were recruited in a five-wave longitudinal study that followed Veterans for up to 16 years after deployment. We used growth curve modeling to investigate trajectories of change in alcohol consumption and dependence risk among men and women Veterans. We examined predictors of growth, including demographics, support and resources, psychiatric symptoms, and trauma exposure. RESULTS: Among male Veterans, alcohol consumption and dependence risk remained stagnant, which is in contrast to past work using non-Veteran samples. For female Veterans, consumption exhibited initial reductions that decelerated, and dependence risk reduced at a continuous rate. PTSD diagnosis was a significant predictor of individual differences in growth for men. Psychiatric symptoms (i.e., PTSD diagnosis, probable depression diagnosis, suicidal ideation) and psychosocial functioning were significant predictors of decreasing alcohol use for women. CONCLUSIONS: Results highlight important sex differences in patterns and predictors of change in alcohol consumption and dependence risk among post-9/11 Veterans. Findings are discussed in relation to screening for hazardous alcohol use and intervention strategies in this at-risk population.

Mutagenesis and functional analysis of the varicella-zoster virus portal protein.

Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZVLUC recombinant viruses (TNs) were generated via recombineering. Insertions were mapped to predicted portal domains (clip, wing, stem, wall, crown, and ß-hairpin tunnel-loop) and recombinant viruses were characterized for plaque morphology, replication kinetics, pORF54 expression, and classified based on replication in non-complementing (ARPE19) or complementing (ARPE54C50) cell lines. The N- and C-termini were tolerant to insertion mutagenesis, as were certain clip sub-domains. The majority of mutants mapping to the wing, wall, ß-hairpin tunnel loop, and stem domains were lethal. Elimination of the predicted ORF54 start codon revealed that the first 40 amino acids of the N-terminus were not required for viral replication. Stop codon insertions in the C-terminus showed that the last 100 amino acids were not required for viral replication. Lastly, a putative protease cleavage site was identified in the C-terminus of pORF54. Cleavage was likely orchestrated by a viral protease; however, processing was not required for DNA encapsidation and viral replication. The panel of recombinants should prove valuable in future studies to dissect mammalian portal structure and function.IMPORTANCEThough nucleoside analogs and a live-attenuated vaccine are currently available to treat some human herpesvirus family members, alternate methods of combating herpesvirus infection could include blocking viral replication at the DNA encapsidation stage. The approval of Letermovir provided proof of concept regarding the use of encapsidation inhibitors to treat herpesvirus infections in the clinic. We propose that small-molecule compounds could be employed to interrupt portal oligomerization, assembly into the capsid vertex, or affect portal function/dynamics. Targeting portal at any of these steps would result in disruption of viral DNA packaging and a decrease or absence of mature infectious herpesvirus particles. The oligomeric portals of herpesviruses are structurally conserved, and therefore, it may be possible to find a single compound capable of targeting portals from one or more of the herpesvirus subfamilies. Drug candidates from such a series would be effective against viruses resistant to the currently available antivirals.

GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV.

BACKGROUND: Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. METHODS: A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. RESULTS: A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss. CONCLUSIONS: Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.

Disorder and Sorption Preferences in a Highly Stable Fluoride-Containing Rare-Earth fcu-Type Metal-Organic Framework.

Rare-earth (RE) metal-organic frameworks (MOFs) synthesized in the presence of fluorine-donating modulators or linkers are an important new subset of functional MOFs. However, the exact nature of the REaXb core of the molecular building block (MBB) of the MOF, where X is a µ2 or 3-bridging group, remains unclear. Investigation of one of the archetypal members of this family with the stable fcu framework topology, Y-fum-fcu-MOF (1), using a combination of experimental techniques, including high-field (20 T) solid-state nuclear magnetic resonance spectroscopy, has determined two sources of framework disorder involving the µ3-X face-capping group of the MBB and the fumarate (fum) linker. The core of the MBB of 1 is shown to contain a mixture of µ3-F- and (OH)- groups with preferential occupation at the crystallographically different face-capping sites that result in different internally lined framework tetrahedral cages. The fum linker is also found to display a disordered arrangement involving bridging- or chelating-bridging bis-bidentate modes over the fum linker positions without influencing the MBB orientation. This linker disorder will, upon activation, result in the creation of Y3+ ions with potentially one or two additional uncoordinated sites possessing differing degrees of Lewis acidity. Crystallographically determined host-guest relationships for simple sorbates demonstrate the favored sorption sites for N2, CO2, and CS2 molecules that reflect the chemical nature of both the framework and the sorbate species with the structural partitioning of the µ3-groups apparent in determining the favored sorption site of CS2. The two types of disorder found within 1 demonstrate the complexity of fluoride-containing RE-MOFs and highlight the possibility to tune this and other frameworks to contain different proportions and segregations of µ3-face-capping groups and degrees of linker disorder for specifically tailored applications.

Cause and preventability of in-hospital mortality after PCI: A statewide root-cause analysis of 1,163 deaths.

BACKGROUND: Mortality is the most devastating complication of percutaneous coronary interventions (PCI). Identifying the most common causes and mechanisms of death after PCI in contemporary practice is an important step in further reducing periprocedural mortality. OBJECTIVES: To systematically analyze the cause and circumstances of in-hospital mortality in a large, multi-center, statewide cohort. METHODS: In-hospital deaths after PCI occurring at 39 hospitals included in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) between 2012 and 2014 were retrospectively reviewed using validated methods. A priori PCI-related mortality risk was estimated using the validated BMC2 model. RESULTS: A total of 1,163 deaths after PCI were included in the study. Mean age was 71±13 years, and 507 (44%) were women. Left ventricular failure was the most common cause of death (52% of cases). The circumstance of death was most commonly related to prior acute cardiovascular condition (61% of cases). Procedural complications were considered contributing to mortality in 235 (20%) cases. Death was rated as not preventable or slightly preventable in 1,045 (89.9%) cases. The majority of the deaths occurred in intermediate or high-risk patients, but 328 (28.2%) deaths occurred in low-risk patients (<5% predicted risk of mortality). PCI was considered rarely appropriate in 30% of preventable deaths. CONCLUSIONS: In-hospital mortality after PCI is rare, and primarily related to pre-existing critical acute cardiovascular condition. However, approximately 10% of deaths were preventable. Further research is needed to characterize preventable deaths, in order to develop strategies to improve procedural safety.