Providing optimal care in the neonatal care units in India: How Covid-19 exacerbated existing barriers.

Nearly one quarter (600,000) of all neonatal deaths worldwide per year occur in India. To reduce neonatal mortality, the Indian Ministry of Health and Family Welfare established neonatal care units, including neonatal intensive care units and specialized neonatal care units to provide immediate care at birth, resuscitation for asphyxiation, postnatal care, follow up for high-risk newborns, immunization, and referral for additional or complex healthcare services. Despite these efforts, neonatal mortality remains high, and measures taken to reduce mortality have been severely challenged by multiple problems caused by the Covid-19 pandemic. In this qualitative study, we conducted seven focus group discussions with newborn care unit nurses and pediatric residents and 35 key informant interviews with pediatricians, residents, nurses, annual equipment maintenance contractors, equipment manufacturers, and Ministry personnel in the Vidarbha region of Maharashtra between December 2019 and November 2020. The goal of the study was to understand barriers and facilitators to providing optimal care to neonates, including the challenges imposed by the Covid-19 pandemic. Covid-19 exacerbated existing barriers to providing optimal care to neonates in these newborn care units. As a result of Covid-19, we found the units were even more short-staffed than usual, with trained pediatric nurses and essential equipment diverted from newborn care to attend to patients with Covid-19. Regular training of neonatal nursing staff was also disrupted due to Covid-19, leaving many staff without the skills to provide optimate care to neonates. Infection control was also exacerbated by Covid-19. This study highlights the barriers to providing optimal care for neonates were made even more challenging during Covid-19 because of the diversion of critically important neonatal equipment and staff trained to use that equipment to Covid-19 wards. The barriers at the individual, facility, and systems levels will remain challenging as the Covid-19 pandemic continues.

Patient Characteristics Associated with Receiving Gender-Affirming Hormone Therapy in the Veterans Health Administration.

Purpose: This study aimed to examine patient characteristics associated with receipt of gender-affirming hormone therapy in the Veterans Health Administration (VHA). Methods: This cross-sectional study included a national cohort of 9555 transgender and gender diverse (TGD) patients with TGD-related diagnosis codes who received care in the VHA from 2006 to 2018. Logistic regression models were used to determine the association of health conditions and documented social stressors with receipt of gender affirming hormone therapy. Results: Of the 9555 TGD patients, 57.4% received gender-affirming hormone therapy in the VHA. In fully adjusted models, patients who had following characteristics were less likely to obtain gender-affirming hormones in the VHA: Black, non-Hispanic versus white (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.52-0.72), living in the Northeast versus the West (aOR: 0.72; 95% CI: 0.62-0.84), a documented drug use disorder (aOR: 0.56; 95% CI: 0.47-0.68), ≥3 versus no comorbidities (aOR: 0.44; 95% CI: 0.34-0.57), and ≥3 versus no social stressors (aOR: 0.42; 95% CI: 0.30-0.58; all p<0.001). Younger patients aged 21-29 years were almost 3 times more likely to receive gender affirming hormone therapy in the VHA than those aged ≥60 (aOR: 2.98; 95% CI: 2.55-3.47; p<0.001). Conclusion: TGD individuals who were older, Black, non-Hispanic, and had more comorbidities and documented social stressors were less likely to receive gender-affirming hormone therapy in the VHA. Further understanding of patient preferences in addition to clinician- and site-level determinants that may impact access to gender-affirming hormone therapy for TGD individuals in the VHA is needed.

The soybean Rpp3 gene encodes a TIR-NBS-LRR protein that confers resistance to Phakopsora pachyrhizi.

Soybean rust is an economically significant disease caused by the fungus Phakopsora pachyrhizi that negatively impacts soybean (Glycine max (L.) Merr.) production throughout the world. Susceptible plants infected by P. pachyrhizi develop tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci (Rpp1 to Rpp7) that provide race-specific resistance to P. pachyrhizi (Rpp) have been identified. Rpp3 was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two Rpp genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the Rpp3 locus to a 371 kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify Rpp3, we designed oligonucleotide primers to amplify Rpp3 candidate (Rpp3C) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five Rpp3C genes were identified in both Rpp3-resistant soybean lines, and co-silencing these genes compromised resistance to P. pachyrhizi. Gene expression analysis and sequence comparisons of the Rpp3C genes in PI 462312 and PI 506764 suggest that a single candidate gene, Rpp3C3, is responsible for Rpp3-mediated resistance.

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir.

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.

Is Abstinence from Alcohol and Smoking Associated with Less Anxiety and Depressive Symptoms Among People with HIV?

Achieving abstinence from alcohol, tobacco, or both may improve mental health, but is understudied in people with HIV (PWH). The St PETER HIV randomized clinical trial compared varenicline, cytisine, and nicotine replacement therapy on alcohol and smoking behavior among 400 PWH in Russia. The primary exposure was thirty-day point prevalence abstinence (PPA) from (1) alcohol, (2) smoking, (3) both, or (4) neither and was assessed at 1, 3, 6 and 12-months as were the study outcomes of anxiety (GAD-7) and depressive (CES-D) symptoms. The primary aim was to examine the association between smoking and/or alcohol abstinence and subsequent symptoms of depression and anxiety. Primary analysis used repeated measures generalized linear modeling to relate PPA with mental health scores across time. In secondary analyses, Kruskal-Wallis tests related PPA with mental health scores at each timepoint. Primary analyses did not identify significant differences in anxiety or depressive symptoms between exposure groups over time. Secondary analyses found CES-D scores across PPA categories were similar at 1-month (11, 10, 11, 11) and 6-months (10, 10, 11, 11) but differed at 3-months (9, 11, 10, 12; p = 0.035) and 12-months (10, 6, 11, 10; p = 0.019). GAD-7 scores did not vary across PPA categories at any time point. While abstinence was associated with fewer depressive symptoms at times, findings were not consistent during follow-up, perhaps reflecting intermittent relapse. PWH with polysubstance use and mental health comorbidity are complex, and larger samples with sustained abstinence would further elucidate effects of abstinence on mental health.

Reliable method for predicting the binding affinity of RNA-small molecule interactions using machine learning.

Ribonucleic acids (RNAs) play important roles in cellular regulation. Consequently, dysregulation of both coding and non-coding RNAs has been implicated in several disease conditions in the human body. In this regard, a growing interest has been observed to probe into the potential of RNAs to act as drug targets in disease conditions. To accelerate this search for disease-associated novel RNA targets and their small molecular inhibitors, machine learning models for binding affinity prediction were developed specific to six RNA subtypes namely, aptamers, miRNAs, repeats, ribosomal RNAs, riboswitches and viral RNAs. We found that differences in RNA sequence composition, flexibility and polar nature of RNA-binding ligands are important for predicting the binding affinity. Our method showed an average Pearson correlation (r) of 0.83 and a mean absolute error of 0.66 upon evaluation using the jack-knife test, indicating their reliability despite the low amount of data available for several RNA subtypes. Further, the models were validated with external blind test datasets, which outperform other existing quantitative structure-activity relationship (QSAR) models. We have developed a web server to host the models, RNA-Small molecule binding Affinity Predictor, which is freely available at: https://web.iitm.ac.in/bioinfo2/RSAPred/.

Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.

Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia.

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.

Can the date of last menstrual period be trusted in the first trimester? Comparisons of gestational age measures from a prospective cohort study in six low-income to middle-income countries.

OBJECTIVES: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries. DESIGN: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based on GA estimated either by LMP or USG and had a live or stillbirth with an estimated GA of 20-42 weeks. OUTCOME MEASURES: GA was estimated in weeks and days based on LMP and/or USG. Prematurity was defined as GA of 20 weeks+0 days through 36 weeks+6 days, calculated by both USG and LMP. RESULTS: Overall, average GA varied ≤1 week between LMP and USG. Mean GA for live births by LMP was lower than by USG (adjusted mean difference (95% CI) = -0.23 (-0.29 to -0.17) weeks). Among stillbirths, a higher GA was estimated by LMP than USG (adjusted mean difference (95% CI)= 0.42 (0.11 to 0.72) weeks). Preterm birth rates for live births were significantly higher when dated by LMP (adjusted rate difference (95% CI)= 4.20 (3.56 to 4.85)). There was no significant difference in preterm birth rates for stillbirths. CONCLUSION: The small differences in GA for LMP versus USG in the Guatemalan and Indian sites suggest that LMP may be a useful alternative to USG for GA dating during the first trimester until availability of USG improves in those areas. Further research is needed to assess LMP for first-trimester GA dating in other regions with limited access to USG. TRIAL REGISTRATION NUMBER: NCT01073475.

Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum ß-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10-10) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Influenza: seasonality and travel-related considerations.

RATIONALE FOR REVIEW: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. KEY FINDINGS: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. CONCLUSIONS/RECOMMENDATIONS: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.

Equitable Access to Telehealth and Other Services for Deaf People During the COVID-19 Pandemic.

Introduction: Deaf people who use American Sign Language (ASL) with low self-perceived ability to understand spoken information face inequitable access to health care due to systemic barriers. Methods: We conducted interviews with 266 deaf ASL users at baseline (May-Aug 2020) and 244 deaf ASL users at follow-up (3 months). Questions addressed (1) access to interpretation during in-person visits; (2) whether they visited clinics (3) or emergency departments (EDs); and (4) telehealth use. Analyses involved univariate and multivariable logistic regressions across levels of perceived ability to understand spoken language. Results: Less than a third were aged >65 (22.8%); Black, Indigenous, People of Color (28.6%), or LGBTQ+ (31.1%); and had no college degree (30.6%). More respondents reported outpatient visits at follow-up (63.9%) than at baseline (42.3%). Ten more respondents reported going to urgent care or an ED at follow-up than at baseline. At follow-up interviews, 57% of deaf ASL respondents with high perceived ability to understand spoken language reported receiving interpretation at clinic visits compared to 32% of ASL respondents with low perceived ability to understand spoken language (p<0.01). Telehealth and ED visits showed no between-group differences for low versus high perceived ability to understand spoken language. Discussion: Our study is the first to explore deaf ASL users' access to telehealth and outpatient encounters over time during the pandemic. The U.S. health care system is designed for people who have high perceived ability to understand spoken information. Systemic access to health care, including telehealth and clinics, must be made consistently equitable for deaf people who require accessible communication.

Development of a prediction model for the acquisition of extended spectrum beta-lactam-resistant organisms in U.S. international travellers.

BACKGROUND: Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies. METHODS: We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition. RESULTS: A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69-0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67-0.69). This model uses traveller's diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors. CONCLUSIONS: We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel.

Erythrocyte miRNA-92a-3p interactions with PfEMP1 as determinants of clinical malaria.

Based on the recently added high throughput analysis data on small noncoding RNAs in modulating disease pathophysiology of malaria, we performed an integrative computational analysis for exploring the role of human-host erythrocytic microRNAs (miRNAs) and their influence on parasite survival and host homeostasis. An in silico analysis was performed on transcriptomic datasets accessed from PlasmoDB and Gene Expression Omnibus (GEO) repositories analyzed using miRanda, miRTarBase, mirDIP, and miRDB to identify the candidate miRNAs that were further subjected to network analysis using MCODE and DAVID. This was followed by immune infiltration analysis and screening for RNA degradation mechanisms. Seven erythrocytic miRNAs, miR-451a, miR-92a-3p, miR-16-5p, miR-142-3p, miR-15b-5p, miR-19b-3p, and miR-223-3p showed favourable interactions with parasite genes expressed during blood stage infection. The miR-92a-3p that targeted the virulence gene PfEMP1 showed drastic reduction during infection. Performing pathway analysis for the human-host gene targets for the miRNA identified TOB1, TOB2, CNOT4, and XRN1 genes that are associated to RNA degradation processes, with the exoribonuclease XRN1, highly enriched in the malarial samples. On evaluating the role of exoribonucleases in miRNA degradation further, the pattern of Plasmodium falciparum_XRN1 showed increased levels during infection thus suggesting a defensive role for parasite survival. This study identifies miR-92a-3p, a member of C13orf25/ miR-17-92 cluster, as a novel miRNA inhibitor of the crucial parasite genes responsible for symptomatic malaria. Evidence for a plausible link to chromosome 13q31.3 loci controlling the epigenetic disease regulation is also suggested.

Understanding Drug Resistance of Wild-Type and L38HL Insertion Mutant of HIV-1 C Protease to Saquinavir.

Acquired immunodeficiency syndrome (AIDS) is one of the most challenging infectious diseases to treat on a global scale. Understanding the mechanisms underlying the development of drug resistance is necessary for novel therapeutics. HIV subtype C is known to harbor mutations at critical positions of HIV aspartic protease compared to HIV subtype B, which affects the binding affinity. Recently, a novel double-insertion mutation at codon 38 (L38HL) was characterized in HIV subtype C protease, whose effects on the interaction with protease inhibitors are hitherto unknown. In this study, the potential of L38HL double-insertion in HIV subtype C protease to induce a drug resistance phenotype towards the protease inhibitor, Saquinavir (SQV), was probed using various computational techniques, such as molecular dynamics simulations, binding free energy calculations, local conformational changes and principal component analysis. The results indicate that the L38HL mutation exhibits an increase in flexibility at the hinge and flap regions with a decrease in the binding affinity of SQV in comparison with wild-type HIV protease C. Further, we observed a wide opening at the binding site in the L38HL variant due to an alteration in flap dynamics, leading to a decrease in interactions with the binding site of the mutant protease. It is supported by an altered direction of motion of flap residues in the L38HL variant compared with the wild-type. These results provide deep insights into understanding the potential drug resistance phenotype in infected individuals.

Therapeutics through glycobiology: an approach for targeted elimination of malaria.

The emergence of drug resistance in Plasmodium jeopardises worldwide malaria eradication efforts necessitating novel therapeutic approaches and therefore the identification of key metabolic pathways of parasite and human host for drug development garners importance. Enzymopathies like glucose-6-phosphate-dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies have been shown to protect against the severe consequences of malaria. Glycome profiles and the regulatory mechanisms involving the microRNAs or transcription factors' expression related to the histo-blood group glycogenes may add up to resolve the underlying pathogenesis. The glycan derivatives viz. heparin-like molecules (HLMs) interrupt parasite proliferation that can be exploited as leads for alternative therapies. The Plasmodium invasion of erythrocytes involve events of receptor recognition, adhesion, and ligand interactions. Since post translational modifications like N-glycosylation of merozoite surface proteins and several erythrocyte cluster of differentiation (CD) antigens and complement receptor, among others, are crucial to parasite invasion, understanding of post translational modification of proteins involved in the parasite-host interactions should identify viable antimalarial strategies.

Caring for Adults With Significant Levels of Intellectual Disability in Outpatient Settings: Results of a National Survey of Physicians.

Between 1% and 2% of the U.S. population has an intellectual disability (ID) and often experience disparities in health care. Communication patterns and sedation use for routine medical procedures are important aspects of care for this population. We explored physicians' communication patterns and sedation use in caring for patients with significant levels of ID through a mailed survey of 1,400 physicians among seven specialties in outpatient settings (response rate = 61.0%). Among physicians who saw at least one patient with significant levels of ID in an average month, 74.8% reported usually/always communicating primarily with someone other than the patient. Among specialists, 85.5% (95% CI: 80.5%-90.5%) reported doing so, compared to 69.9% (95% CI: 64.4%-75.4%) for primary care physicians (p < 0.001). Also, 11.4% reported sedating at least one patient with significant levels of ID for a routine procedure. Three quarters of physicians reported communicating primarily with persons other than the patient usually or always-an approach that, in some instances, may not align with best medical practice. The percentage of physicians who report sedating at least one individual is associated with significant ID and the physician's volume of patients with significant ID.

Accommodating hearing loss in outpatient physician offices in the U.S.

BACKGROUND: Approximately 16.2 million Americans ages 18 and older (5.7%) report being deaf or having serious difficulty hearing. Hearing loss impedes effective communication during clinical encounters putting patients' safety at risk. A large fraction of Americans with Disabilities Act lawsuits addresses whether providers offered auxiliary aids and services required to ensure effective communication. OBJECTIVE: Examine use of different hearing accommodations for deaf or hard of hearing patients by U.S. physicians. METHODS: We surveyed randomly selected physicians nationwide representing 7 specialties about their reported use of 8 types of accommodations when communicating with adult outpatients who are deaf or have significant difficulty hearing, even with hearing aids (overall weighted response rate = 61.0%). We performed a descriptive analysis of responses, using survey sampling weights. RESULTS: Among the 526 physicians in this analysis, most were male, white, urban, and practiced in community-based practices. Overall, 81.5% (SE = 1.9) reported that patients with significant hearing limitations get worse quality health care than others. Among participants, 49.8% (2.4) reported never using an in-person sign language interpreter hired by the practice, and 63.2% (2.4) never use video remote interpreting. In contrast, 30.7% (2.1) always and 29.8% (2.2) usually speak louder and slower to patients with significant hearing limitations. None of the 8 accommodations were always or usually used by 8.9% (1.3) of participants. CONCLUSIONS: More than 32 years after the Americans with Disabilities Act, most physicians do not offer accommodations sufficient to ensure effective communication with adult outpatients with significant hearing limitations.

Social Stressors and Health Among Older Transgender and Gender Diverse Veterans.

Purpose: Health disparities in transgender and gender diverse (TGD) veterans compared with cisgender veterans have been documented. However, there is a paucity of literature focused on older TGD veterans. We assessed health conditions and social stressors in older TGD veterans compared with matched cisgender veterans. Methods: Using gender identity disorder diagnosis codes, we identified 1244 TGD veterans (65+ years of age) receiving care in the Veterans Health Administration (VHA) from 2006 to 2018. These TGD veterans were then matched to 3732 cisgender veterans based on age, VHA site, and date of care in VHA. Results: In adjusted models, TGD veterans compared with cisgender veterans were less likely to have alcohol use disorder (adjusted odds ratio [AOR; 95% confidence interval]: [0.70; 0.58-0.85]), drug use disorder (0.59; 0.47-0.74), tobacco use (0.75; 0.65-0.86), and anxiety (0.74; 0.62-0.90). However, compared with cisgender veterans, TGD veterans were more likely to experience depression (1.63; 1.39-1.93), Alzheimer's disease (8.95; 4.25-18.83), cancer (1.83; 1.56-2.14), violence (1.82; 1.14-2.91), social/familial problems (2.45; 1.99-3.02), lack of access to care/transportation (2.23; 1.48-3.37), and military sexual trauma (2.59; 1.93-3.46). Furthermore, compared with cisgender veterans, TGD veterans were more likely to have documentation of a higher count of social stressors: 1 or more stressors (1.64; 1.38-1.95) and 2 or more stressors (1.22; 1.01-1.49). Conclusion: Despite significant disparities in social stressors and health conditions compared with cisgender veterans, TGD veterans had a lower likelihood of substance use and anxiety. Interventions are needed to mitigate social stressors and improve health among the older TGD veteran population.

The Role of the US Trauma Centers in Older Adult Fall Prevention: A National Survey.

INTRODUCTION: Approximately 27.5% of adults 65 and older fall each year, over 3 million are treated in an emergency department, and 32 000 die. The American College of Surgeons and its Committee on Trauma (ACSCOT) have urged trauma centers (TCs) to screen for fall risk, but information on the role of TC in this opportunity for prevention is largely unknown. METHODS: A 29-item survey was developed by an ACSCOT Injury Prevention and Control Committee, Older Adult Falls workgroup, and emailed to 1000 trauma directors of the National Trauma Data Bank using Qualtrics. US TCs were surveyed regarding fall prevention, screening, intervention, and hospital discharge practices. Data collected and analyzed included respondent's role, location, population density, state designation or American College of Surgeons (ACS) level, if teaching facility, and patient population. RESULTS: Of the 266 (27%) respondents, 71% of TCs include fall prevention as part of their mission, but only 16% of TCs use fall risk screening tools. There was no significant difference between geographic location or ACS level. The number of prevention resources (F = 31.58, P < .0001) followed by the presence of a formal screening tool (F = 21.47, P < .0001) best predicted the presence of a fall prevention program. CONCLUSION: Older adult falls remain a major injury risk and injury prevention opportunity. The majority of TCs surveyed include prevention of older adult falls as part of their mission, but few incorporate the components of a fall prevention program. Development of best practices and requiring TCs to screen and offer interventions may prevent falls.