Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating.

CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ∼ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large Mg(2+)-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg(2+)-bound closed conformation and in two open Mg(2+)-free states at resolutions of 3.8, 7.1, and 7.1 Å, respectively. In the absence of bound Mg(2+), four of the five subunits are displaced to variable extents (∼ 10-25 Å) by hinge-like motions as large as ∼ 35° at the stalk helix. The transition between a single 5-fold symmetric closed state and an ensemble of low Mg(2+), open, asymmetric conformational states is, thus, the key structural signature of CorA gating. This mechanism is likely to apply to other structurally similar divalent ion channels.

Bulky hydrophobic side chains in the ß1-sandwich of microsomal triglyceride transfer protein are critical for the transfer of both triglycerides and phospholipids.

Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglyceride (TG) and not phospholipid (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different ß-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in ß2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in ß1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, whereas negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention.

MicroRNA-615-3p decreases apo B expression in human liver cells.

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels are associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3'-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion.

In Silico Screening, Molecular Dynamics Simulation and Binding Free Energy Identify Single-Point Mutations That Destabilize p53 and Reduce Binding to DNA.

Considering p53's pivotal role as a tumor suppressor protein, proactive identification and characterization of potentially harmful p53 mutations are crucial before they appear in the population. To address this, four computational prediction tools-SIFT, Polyphen-2, PhD-SNP, and MutPred2-utilizing sequence-based and machine-learning algorithms, were employed to identify potentially deleterious p53 nsSNPs (nonsynonymous single nucleotide polymorphisms) that may impact p53 structure, dynamics, and binding with DNA. These computational methods identified three variants, namely, C141Y, C238S, and L265P, as detrimental to p53 stability. Furthermore, molecular dynamics (MD) simulations revealed that all three variants exhibited heightened structural flexibility compared to the native protein, especially the C141Y and L265P mutations. Consequently, due to the altered structure of mutant p53, the DNA-binding affinity of all three variants decreased by approximately 1.8 to 9.7 times compared to wild-type p53 binding with DNA (14 µM). Notably, the L265P mutation exhibited an approximately ten-fold greater reduction in binding affinity. Consequently, the presence of the L265P mutation in p53 could pose a substantial risk to humans. Given that p53 regulates abnormal tumor growth, this research carries significant implications for surveillance efforts and the development of anticancer therapies.

Glycemic Management in Insulin-Naive Patients in the Inpatient Setting.

Objective: The ideal inpatient insulin regimen efficiently attains the target blood glucose range, effectively treats hyperglycemia, and minimizes the risk of hypoglycemia. The objective of this study was to compare glycemic targets achieved by using correctional monotherapy (CM) and basal-bolus therapy (BBT) in insulin-naive patients in the inpatient setting to determine optimal blood glucose management for these patients. Design: This was a retrospective observational cohort study of 792 patients with diabetes not on home insulin therapy who were admitted to an academic hospital over a 5.5-month period. The percentages of hyperglycemic and hypoglycemic values in each group were compared. Results: Among the 3,112 measured blood glucose values obtained from 792 patients within the first 24 hours of insulin administration, 28.5% were hyperglycemic in the BBT group compared with 23.5% in the CM group. When adjusted for covariates, there was a 23% decrease in hyperglycemia in the BBT group (incidence rate ratio = 0.77, 95% CI 0.64-0.95, P = 0.006). Increases in A1C and admission blood glucose, as well as decreases in admission creatinine and inpatient steroid use, were independently associated with higher rates of hyperglycemia, adjusted for all other covariates. There was no significant difference between the groups in the rate of hypoglycemia in the first 24 hours, which was 1.9% in the BBT group and 1.4% in the CM group (P = 0.301). Conclusion: Utilizing BBT in insulin-naive patients admitted to the hospital within the first 24 hours of insulin administration results in lower rates of hyperglycemia without higher rates of hypoglycemia when compared with CM.

Wheat Water-Soluble Carbohydrate Remobilisation under Water Deficit by 1-FEH w3.

Fructan 1-exohydrolase (1-FEH) is one of the major enzymes in water-soluble carbohydrate (WSC) remobilisation for grains in wheat. We investigated the functional role of 1-FEH w1, w2, and w3 isoforms in WSC remobilisation under post-anthesis water deficit using mutation lines derived from the Australian wheat variety Chara. F1 seeds, developed by backcrossing the 1-FEH w1, w2, and w3 mutation lines with Chara, were genotyped using the Infinium 90K SNP iSelect platform to characterise the mutated region. Putative deletions were identified in FEH mutation lines encompassing the FEH genomic regions. Mapping analysis demonstrated that mutations affected significantly longer regions than the target FEH gene regions. Functional roles of the non-target genes were carried out utilising bioinformatics and confirmed that the non-target genes were unlikely to confound the effects considered to be due to the influence of 1-FEH gene functions. Glasshouse experiments revealed that the 1-FEH w3 mutation line had a slower degradation and remobilisation of fructans than the 1-FEH w2 and w1 mutation lines and Chara, which reduced grain filling and grain yield. Thus, 1-FEH w3 plays a vital role in reducing yield loss under drought. This insight into the distinct role of the 1-FEH isoforms provides new gene targets for water-deficit-tolerant wheat breeding.

The putative vacuolar processing enzyme gene TaVPE3cB is a candidate gene for wheat stem pith-thickness.

KEY MESSAGE: The vacuolar processing enzyme gene TaVPE3cB is identified as a candidate gene for a QTL of wheat pith-thickness on chromosome 3B by BSR-seq and differential expression analyses. The high pith-thickness (PT) of the wheat stem could greatly enhance stem mechanical strength, especially the basal internodes which support the heavier upper part, such as upper stems, leaves and spikes. A QTL for PT in wheat was previously discovered on 3BL in a double haploid population of 'Westonia' × 'Kauz'. Here, a bulked segregant RNA-seq analysis was applied to identify candidate genes and develop associated SNP markers for PT. In this study, we aimed at screening differentially expressed genes (DEGs) and SNPs in the 3BL QTL interval. Sixteen DEGs were obtained based on BSR-seq and differential expression analyses. Twenty-four high-probability SNPs in eight genes were identified by comparing the allelic polymorphism in mRNA sequences between the high PT and low PT samples. Among them, six genes were confirmed to be associated with PT by qRT-PCR and sequencing. A putative vacuolar processing enzyme gene TaVPE3cB was screened out as a potential PT candidate gene in Australian wheat 'Westonia'. A robust SNP marker associated with TaVPE3cB was developed, which can assist in the introgression of TaVPE3cB.b in wheat breeding programs. In addition, we also discussed the function of other DEGs which may be related to pith development and programmed cell death (PCD). A five-level hierarchical regulation mechanism of stem pith PCD in wheat was proposed.

Discovery of Nirmatrelvir Resistance Mutations in SARS-CoV-2 3CLpro: A Computational-Experimental Approach.

The COVID-19 pandemic has emphasized the urgency for effective antiviral therapies against SARS-CoV-2. Targeting the main protease (3CLpro) of the virus has emerged as a promising approach, and nirmatrelvir (PF-07321332), the active component of Pfizer's oral drug Paxlovid, has demonstrated remarkable clinical efficacy. However, the emergence of resistance mutations poses a challenge to its continued success. In this study, we employed alchemical free energy perturbation (FEP) alanine scanning to identify nirmatrelvir-resistance mutations within SARS-CoV-2 3CLpro. FEP identified several mutations, which were validated through in vitro IC50 experiments and found to result in 8- and 72-fold increases in nirmatrelvir IC50 values. Additionally, we constructed SARS-CoV-2 omicron replicons containing these mutations, and one of the mutants (S144A/E166A) displayed a 20-fold increase in EC50, confirming the role of FEP in identifying drug-resistance mutations. Our findings suggest that FEP can be a valuable tool in proactively monitoring the emergence of resistant strains and guiding the design of future inhibitors with reduced susceptibility to drug resistance. As nirmatrelvir is currently widely used for treating COVID-19, this research has important implications for surveillance efforts and antiviral development.

Increased Wheat Protein Content via Introgression of an HMW Glutenin Selectively Reshapes the Grain Proteome.

Introgression of a high-molecular-weight glutenin subunit (HMW-GS) allele, 1Ay21∗, into commercial wheat cultivars increased overall grain protein content and bread-making quality, but the role of proteins beyond this HMW-GS itself was unknown. In addition to increased abundance of 1Ay HMW-GS, 115 differentially accumulated proteins (DAPs) were discovered between three cultivars and corresponding introgressed near-isogenic lines. Functional category analysis showed that the DAPs were predominantly other storage proteins and proteins involved in protein synthesis, protein folding, protein degradation, stress response, and grain development. Nearly half the genes encoding the DAPs showed strong coexpression patterns during grain development. Promoters of these genes are enriched in elements associated with transcription initiation and light response, indicating a potential connection between these cis-elements and grain protein accumulation. A model of how this HMW-GS enhances the abundance of machinery for protein synthesis and maturation during grain filling is proposed. This analysis not only provides insights into how introgression of the 1Ay21∗ improves grain protein content but also directs selection of protein candidates for future wheat quality breeding programs.

RNAMotifContrast: a method to discover and visualize RNA structural motif subfamilies.

Understanding the 3D structural properties of RNAs will play a critical role in identifying their functional characteristics and designing new RNAs for RNA-based therapeutics and nanotechnology. While several existing computational methods can help in the analysis of RNA properties by recognizing structural motifs, they do not provide the means to compare and contrast those motifs extensively. We have developed a new method, RNAMotifContrast, which focuses on analyzing the similarities and variations of RNA structural motif characteristics. In this method, a graph is formed to represent the similarities among motifs, and a new traversal algorithm is applied to generate visualizations of their structural properties. Analyzing the structural features among motifs, we have recognized and generalized the concept of motif subfamilies. To asses its effectiveness, we have applied RNAMotifContrast on a dataset of known RNA structural motif families. From the results, we observed that the derived subfamilies possess unique structural variations while holding standard features of the families. Overall, the visualization approach of this method presents a new perspective to observe the relation among motifs more closely, and the discovered subfamilies provide opportunities to achieve valuable insights into RNA's diverse roles.

Proportion of Malignancy and Evaluation of Sonographic Features of Thyroid Nodules Classified as Highly Suspicious Using ACR TI-RADS Criteria.

OBJECTIVES: The reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI-RADS criteria (TI-RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy. METHODS: Our single-institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1-year period. Sonographic features and total TI-RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features. RESULTS: Of the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4-25.2%) were malignant. Each additional TI-RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13-1.60, P < .001). "Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while "punctate echogenic foci" had the lowest positive predictive value (20.0%). CONCLUSIONS: The rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI-RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.

Smart Crop Cultivation System Using Automated Agriculture Monitoring Environment in the Context of Bangladesh Agriculture.

The Internet of Things (IoT) is a transformative technology that is reshaping industries and daily life, leading us towards a connected future that is full of possibilities and innovations. In this paper, we present a robust framework for the application of Internet of Things (IoT) technology in the agricultural sector in Bangladesh. The framework encompasses the integration of IoT, data mining techniques, and cloud monitoring systems to enhance productivity, improve water management, and provide real-time crop forecasting. We conducted rigorous experimentation on the framework. We achieve an accuracy of 87.38% for the proposed model in predicting data harvest. Our findings highlight the effectiveness and transparency of the framework, underscoring the significant potential of the IoT in transforming agriculture and empowering farmers with data-driven decision-making capabilities. The proposed framework might be very impactful in real-life agriculture, especially for monsoon agriculture-based countries like Bangladesh.

Wheat glutamine synthetase TaGSr-4B is a candidate gene for a QTL of thousand grain weight on chromosome 4B.

KEY MESSAGE: Glutamine synthetase TaGSr-4B is a candidate gene for a QTL of thousand grain weight on 4B, and the gene marker is ready for wheat breeding. A QTL for thousand grain weight (TGW) in wheat was previously mapped on chromosome 4B in a DH population of Westonia × Kauz. For identifying the candidate genes of the QTL, wheat 90 K SNP array was used to saturate the existing linkage map, and four field trials plus one glasshouse experiment over five locations were conducted to refine the QTL. Three nitrogen levels were applied to two of those field trials, resulting in a TGW phenotype data set from nine environments. A robust TGW QTL cluster including 773 genes was detected in six environments with the highest LOD value of 13.4. Based on differentiate gene expression within the QTL cluster in an RNAseq data of Westonia and Kauz during grain filling, a glutamine synthesis gene (GS: TaGSr-4B) was selected as a potential candidate gene for the QTL. A SNP on the promoter region between Westonia and Kauz was used to develop a cleaved amplified polymorphic marker for TaGSr-4B gene mapping and QTL reanalysing. As results, TGW QTL appeared in seven environments, and in four out of seven environments, the TGW QTL were localized on the TaGSr-4B locus and showed significant contributions to the phenotype. Based on the marker, two allele groups of Westonia and Kauz formed showed significant differences on TGW in eight environments. In agreement with the roles of GS genes on nitrogen and carbon remobilizations, TaGSr-4B is likely the candidate gene of the TGW QTL on 4B and the TaGSr-4B gene marker is ready for wheat breeding.

Coronavirus Disease 2019 and the Injured Patient: A Multicenter Review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been shown to affect outcomes among surgical patients. We hypothesized that COVID-19 would be linked to higher mortality and longer length of stay of trauma patients regardless of the injury severity score (ISS). METHODS: We performed a retrospective analysis of trauma registries from two level 1 trauma centers (suburban and urban) from March 1, 2019, to June 30, 2019, and March 1, 2020, to June 30, 2020, comparing baseline characteristics and cumulative adverse events. Data collected included ISS, demographics, and comorbidities. The primary outcome was time from hospitalization to in-hospital death. Outcomes during the height of the first New York COVID-19 wave were also compared with the same time frame in the prior year. Kaplan-Meier method with log-rank test and Cox proportional hazard models were used to compare outcomes. RESULTS: There were 1180 trauma patients admitted during the study period from March 2020 to June 2020. Of these, 596 were never tested for COVID-19 and were excluded from the analysis. A total of 148 COVID+ patients and 436 COVID- patients composed the 2020 cohort for analysis. Compared with the 2019 cohort, the 2020 cohort was older with more associated comorbidities, more adverse events, but lower ISS. Higher rates of historical hypertension, diabetes, neurologic events, and coagulopathy were found among COVID+ patients compared with COVID- patients. D-dimer and ferritin were unreliable indicators of COVID-19 severity; however, C-reactive protein levels were higher in COVID+ relative to COVID- patients. Patients who were COVID+ had a lower median ISS compared with COVID- patients, and COVID+ patients had higher rates of mortality and longer length of stay. CONCLUSIONS: COVID+ trauma patients admitted to our two level 1 trauma centers had increased morbidity and mortality compared with admitted COVID- trauma patients despite age and lower ISS. C-reactive protein may play a role in monitoring COVID-19 activity in trauma patients. A better understanding of the physiological impact of COVID-19 on injured patients warrants further investigation.

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk.

BACKGROUND: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Assessment of Safety of Remdesivir in Covid - 19 Patients with Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min per 1.73†m2.

PURPOSE: Safety of remdesivir in patients with renal impairment is unknown. Incidence of liver injury secondary to remdesivir is also unknown. The objective of this study is to assess the incidence of acute kidney injury (AKI) and to trend the liver enzymes during remdesivir treatment and change in eGFR from baseline to end of treatment as well as 48 h post completion of remdesivir therapy. METHODS: This is a retrospective chart review study including adult patients admitted with COVID-19 receiving remdesivir with a baseline eGFR < 30 ml/min per 1.73 m^2 from December 2020 to May 2021. The primary outcome was to assess the incidence of AKI and hepatic injury. The secondary outcome was to assess the efficacy of remdesivir defined by change in oxygen requirement. RESULTS: Seventy-one patients were included in the study. Patients experienced an improvement in eGFR from baseline (T0) to end of remdesivir treatment (T1), as well as 48 h after the end of the treatment (T2) ( + 30.3% and + 30.6% respectively, P < .0001). Creatinine reduced from baseline (T0) to T1 and T2 (-20.9% and -20.5% respectively, P < .0001). Creatinine clearance improved from baseline to T1 and T2 ( + 26.6% and + 26.2% respectively, p < .0001). Elevation of aminotransferase (AST) was observed at T1 ( + 2.5%, P = .727), however, AST reduction was seen at T2 (-15.8%, P = .021). Elevation in alanine transaminase (ALT) was observed at T1 and T2 ( + 25% and + 12%, P = .004 and P = .137 respectively). Both direct and total bilirubin remained stable and were not significantly changed from baseline. CONCLUSION: Our study showed that remdesivir use in renally-impaired patients with eGFR < 30 ml/min is safe. Remdesivir may be considered as a therapeutic option in this population with COVID-19 infection.

Utility of Thyroid Function Testing in the Inpatient Setting.

OBJECTIVE: Previous studies have reported a low value of ordering inpatient thyroid function tests (TFTs), with few changes in clinical management resulting from these tests. This study was designed to evaluate how often testing the thyroid function during hospitalization leads to medication initiation or adjustment and to determine whether the frequency of medication initiation or adjustment differs based on the indication for testing. METHODS: This is a retrospective observational study of 2278 patients who underwent TFTs tested while admitted to an academic hospital during a 5-month period. The indications for ordering TFTs were determined by reviewing clinical documentation, and those with abnormal test results were reviewed to assess whether thyroid medication was initiated or adjusted. RESULTS: The percentage of abnormal TFTs that led to medication initiation or adjustment was 15.1%, 12.2%, and 6.0%, for those tested based on a history of functional thyroid disease, suspicion of thyroid dysfunction, and reasons not directly related to thyroid dysfunction, respectively. Overall, 63 patients were started on thyroid medication or had their thyroid medication dose adjusted, which represented 10.1% of those with abnormal TFTs and only 2.8% of those tested. CONCLUSION: Abnormal TFTs are common, but a disproportionate number of tests are needed to find a small percentage of clinically significant thyroid dysfunction, of which only a low percentage leads to changes in management. Education on this topic should be provided to inpatient providers to limit thyroid function testing to instances in which they are clinically indicated and abnormal results would lead to changes in management.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation.

BACKGROUND: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. METHODS: Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. RESULTS: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. CONCLUSION: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Key Considerations in Ensuring a Safe Regional Telehealth Care Model: A Systematic Review.

Background: This literature review sets out to increase the knowledge on patient safety within the telehealth modality of care, to inform the relevant local health service departments on the key considerations to minimize patient harm. Methods: A systematic search in Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar, and the University of New England (UNE) Library Search was conducted. A combination of key terms "Telehealth" OR "Telecare" OR "Telemedicine" AND "patient safety" AND "rural" was used. Based on the screening and eligibility criteria, 21 peer-reviewed articles published in English between 2015 and 2020 were included in the review. Results and Discussion: On evaluating the included studies, three main themes and various corresponding subthemes emerged. The main themes were that of telehealth experience (TE), telehealth outcomes (TO), and telehealth risks (TR), with the corresponding subthemes of telehealth experience from a patient perspective (TE-PT), telehealth experience from a carer perspective (TE-CR), telehealth experience from a clinician perspective (TE-CN), positive telehealth (TO-P), and negative telehealth outcomes (TO-N), and patient (TR-PT) and clinician telehealth risks (TR-CN). Conclusions: The results suggest that patients generally have positive experiences and are accepting telehealth as a modality of care. Furthermore, patient outcomes appear to be comparable with in-person care, with additional benefits of lower costs to both the service and patients.

Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh.

Secretor status controls mucosal histo-blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings. Clinical Trials Registration. NCT01375647.