Tree species explain only half of explained spatial variability in plant water sensitivity.

Spatiotemporal patterns of plant water uptake, loss, and storage exert a first-order control on photosynthesis and evapotranspiration. Many studies of plant responses to water stress have focused on differences between species because of their different stomatal closure, xylem conductance, and root traits. However, several other ecohydrological factors are also relevant, including soil hydraulics, topographically driven redistribution of water, plant adaptation to local climatic variations, and changes in vegetation density. Here, we seek to understand the relative importance of the dominant species for regional-scale variations in woody plant responses to water stress. We map plant water sensitivity (PWS) based on the response of remotely sensed live fuel moisture content to variations in hydrometeorology using an auto-regressive model. Live fuel moisture content dynamics are informative of PWS because they directly reflect vegetation water content and therefore patterns of plant water uptake and evapotranspiration. The PWS is studied using 21,455 wooded locations containing U.S. Forest Service Forest Inventory and Analysis plots across the western United States, where species cover is known and where a single species is locally dominant. Using a species-specific mean PWS value explains 23% of observed PWS variability. By contrast, a random forest driven by mean vegetation density, mean climate, soil properties, and topographic descriptors explains 43% of observed PWS variability. Thus, the dominant species explains only 53% (23% compared to 43%) of explainable variations in PWS. Mean climate and mean NDVI also exert significant influence on PWS. Our results suggest that studies of differences between species should explicitly consider the environments (climate, soil, topography) in which observations for each species are made, and whether those environments are representative of the entire species range.

Gut community structure as a risk factor for infection in Klebsiella pneumoniae-colonized patients.

The primary risk factor for infection with members of the Klebsiella pneumoniae species complex is prior gut colonization, and infection is often caused by the colonizing strain. Despite the importance of the gut as a reservoir for infectious K. pneumoniae, little is known about the association between the gut microbiome and infection. To explore this relationship, we undertook a case-control study comparing the gut community structure of K. pneumoniae-colonized intensive care and hematology/oncology patients. Cases were K. pneumoniae-colonized patients infected by their colonizing strain (N = 83). Controls were K. pneumoniae-colonized patients who remained asymptomatic (N = 149). First, we characterized the gut community structure of K. pneumoniae-colonized patients agnostic to case status. Next, we determined that gut community data is useful for classifying cases and controls using machine learning models and that the gut community structure differed between cases and controls. K. pneumoniae relative abundance, a known risk factor for infection, had the greatest feature importance, but other gut microbes were also informative. Finally, we show that integration of gut community structure with bacterial genotype data enhanced the ability of machine learning models to discriminate cases and controls. Interestingly, inclusion of patient clinical variables failed to improve the ability of machine learning models to discriminate cases and controls. This study demonstrates that including gut community data with K. pneumoniae-derived biomarkers improves our ability to classify infection in K. pneumoniae-colonized patients.IMPORTANCEColonization is generally the first step in pathogenesis for bacteria with pathogenic potential. This step provides a unique window for intervention since a given potential pathogen has yet to cause damage to its host. Moreover, intervention during the colonization stage may help alleviate the burden of therapy failure as antimicrobial resistance rises. Yet, to understand the therapeutic potential of interventions that target colonization, we must first understand the biology of colonization and if biomarkers at the colonization stage can be used to stratify infection risk. The bacterial genus Klebsiella includes many species with varying degrees of pathogenic potential. Members of the K. pneumoniae species complex have the highest pathogenic potential. Patients colonized in their gut by these bacteria are at higher risk of subsequent infection with their colonizing strain. However, we do not understand if other members of the gut microbiota can be used as a biomarker to predict infection risk. In this study, we show that the gut microbiota differs between colonized patients who develop an infection versus those who do not. Additionally, we show that integrating gut microbiota data with bacterial factors improves the ability to classify infections. Surprisingly, patient clinical factors were not useful for classifying infections alone or when added to microbiota-based models. This indicates that the bacterial genotype and the microbial community in which it exists may determine the progression to infection. As we continue to explore colonization as an intervention point to prevent infections in individuals colonized by potential pathogens, we must develop effective means for predicting and stratifying infection risk.

Loss of RAB25 Cooperates with Oncogenes in the Transformation of Human Mammary Epithelial Cells (HMECs) to Give Rise to Claudin-Low Tumors.

The loss of RAB25 expression-RAS superfamily of GTPase characteristic of numerous breast cancers-corresponds with H-RAS point mutations, particularly in triple-negative breast cancers (TNBC), a subtype associated with a poor prognosis. To address the poorly understood factors dictating the progression of TNBC tumors, we examine the cooperative effects that loss of RAB25 expression in human mammary epithelial cell (HMEC) lines with H-RAS mutations confers in tumorigenesis. HMECs were immortalized by transduction with LXSN CDK4 R24C, a mutant form of cyclin-dependent kinase, followed by transduction with hTERT, a catalytic subunit of the telomerase enzyme. We found that with the loss of RAB25 and overexpression of mutant H-RAS61L, immortal HMECs transformed toward anchorage-independent growth and acquired an increased ability to migrate. Furthermore, cells express low CD24, high CD44, and low claudin levels, indicating stem-like properties upon transformation. Besides, loss of RAB25 and overexpression of H-RAS61L resulted in increased expression of transcription factors Snail and Slug that drive these cells to lose E-cadherin and undergo epithelial-mesenchymal transition (EMT). This study confirms that loss of RAB25 and overexpression of mutant H-RAS can drive HMECs toward a mesenchymal stem-like state. Our findings reveal that RAB25 functions as a tumor suppressor gene, and loss of RAB25 could serve as a novel biomarker of the claudin-low type of TNBC.

Identification and Characterization of Immune Checkpoint Inhibitor-Induced Toxicities From Electronic Health Records Using Natural Language Processing.

PURPOSE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in the real-world data setting is critical for characterizing the benefit/risk profile of ICI therapies beyond the clinical trial population. Diagnosis codes, such as International Classification of Diseases codes, do not comprehensively illustrate a patient's care journey and offer no insight into drug-irAE causality. This study aims to capture the relationship between ICIs and irAEs more accurately by using augmented curation (AC), a natural language processing-based innovation, on unstructured data in electronic health records. METHODS: In a cohort of 9,290 patients treated with ICIs at Mayo Clinic from 2005 to 2021, we compared the prevalence of irAEs using diagnosis codes and AC models, which classify drug-irAE pairs in clinical notes with implied textual causality. Four illustrative irAEs with high patient impact-myocarditis, encephalitis, pneumonitis, and severe cutaneous adverse reactions, abbreviated as MEPS-were analyzed using corticosteroid administration and ICI discontinuation as proxies of severity. RESULTS: For MEPS, only 70% (n = 118) of patients found by AC were also identified by diagnosis codes. Using AC models, patients with MEPS received corticosteroids for their respective irAE 82% of the time and permanently discontinued the ICI because of the irAE 35.9% (n = 115) of the time. CONCLUSION: Overall, AC models enabled more accurate identification and assessment of patient impact of ICI-induced irAEs not found using diagnosis codes, demonstrating a novel and more efficient strategy to assess real-world clinical outcomes in patients treated with ICIs.

Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease.

BACKGROUND: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS: We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 µg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES: Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

Detection of ABO Blood Groups From Dentin and Pulp by Using the Absorption-Elution Technique: A Forensic Cross-Sectional Study Among the Population of the Al Jouf Province, Saudi Arabia.

Background and objective Human teeth have a significant forensic importance. As they are the hardest of all human tissues, they are not just chemically stable but also their characteristics are maintained for a long time after death even in the most harsh environmental conditions. Despite the advances made in DNA analysis, fingerprinting, etc., ABO blood grouping still plays a significant role in the forensic practice in the field of personal identification, paternity disputes, and several other scenarios including the identification of mass disaster victims. The term blood groups refers to inherited antigens on the surface of red blood cells (RBCs) detected by specific antibodies. Since tooth pulp contains numerous blood vessels, blood group antigens are most certainly bound to be present in tooth pulp. Various studies have shown that blood group antigens in the pulp and dentin are preserved as long as up to two years after the demise of an individual. Absorption-elution technique has been proven to be the most sensitive, reliable, and consistent method to determine the ABO blood group from both the pulp and dentine. This study aimed to ascertain the ABO blood group from both the hard (dentin) as well as the soft tissue (pulp) of the tooth by using the absorption-elution (AE) technique and also to determine if there are any variations in identifying the blood groups from the teeth based on age and gender. Material and methods After obtaining due consent, we included patients of both genders aged between 16-60 years visiting the outpatient department (OPD) clinics at the College of Dentistry for periodontal or orthodontic extractions. One patient's blood type was determined by using the slide agglutination technique before any capillary blood extraction was performed; this patient served as a control. For this investigation, we used the pulp and powdered dentin samples taken from the dental extractions to test for the presence of ABO and Rhesus (Rh) factor antigens by using the AE method. The study samples were compared with the control for blood group determination. Statistical analysis was carried out using the chi-square test with Monte Carlo (MC) simulation to check for any correlation of blood grouping with age and gender. Results The dentin and pulp were shown to have positive blood group antigens for the ABO and Rh factors. While neither pulp nor dentin performed significantly differently in identifying the blood group antigens, pulp showed marginally higher accuracy. There was no discernible difference regarding gender or age in the dentin or pulp of any of the 45 samples studied. Conclusions For determining an individual's blood type and Rh factor, both the hard (dentin) and soft (pulp) tissues of a tooth are valid sources. This is particularly helpful in forensic medicine cases where teeth are the only remains that can be viably used to find out a person's identity.

Standards for fecal microbiota transplant: Tools and therapeutic advances.

Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.

Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Analysis of Gender Dimorphism and Assessment of Racial Variation Through Odontometric Technique: A Cross-Sectional Study.

BACKGROUND: When conducting a forensic investigation, one of the most important steps is establishing the biological profile of a victim who cannot be positively recognized or is just a skeleton. It has been shown that, among the other clinical indicators, the diameters of dental crowns are a good and dependable source for determining gender in a particular population sample. However, the literature is sparse regarding their assessment as a viable marker for the determination of a particular race. In addition, the need for population-specific data has also been advocated while determining gender dimorphism based on tooth size. AIM AND OBJECTIVES: To study the bisexual variation in the permanent dentition of individuals from three different sets of populations: Arabian, South Asian, and East Asian. The other objective is to explore the role of this odontometric analysis in predicting the racial identity of the subjects belonging to the aforementioned population. METHODOLOGY: The research was conducted at the College of Dentistry, AlJouf University in Sakaka. Measurements of mesiodistal and buccolingual (BL) distances were taken using a digital vernier caliper on a total of 75 pairs of research models or casts. Statistical tests were run on the information gathered. RESULTS: Of the 75 casts, 38 (50.7%) were of male and 37 (49.3%) were of female. Our analysis showed between genders, a significant difference in maxillary central incisor (P = 0.001), first premolar (P = 0.01), and first molar (P = 0.02) while for a mandibular arch, a significant difference was noted for incisors (P = 0.002) with greater tooth dimension in male than in the female. Concerning the BL dimensions, only the mandibular canine showed a significant difference between males and females (P = 0.001). Comparisons of the crown dimensions between population groups showed that the Arabian population consistently exhibits larger tooth dimensions than the other two populations in both arches. CONCLUSION: A few crown dimensions can be used as an adjunctive tool for the identification of the gender and race of an individual.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Quality of life following treatment with intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer.

OBJECTIVES: Studies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures. METHODS: Three sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years. RESULTS: Treatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety. SIGNIFICANCE OF RESULTS: The combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Voting with their feet: Primary care provider choice and its implications for public sector primary care services in India.

Expanding networks of government primary health centers (PHCs) to bring health services closer to communities is a longstanding policy objective in LMICs. In pluralistic health systems, where public and private providers compete for patients, PHCs are often not the preferred source for care. This study analyzes the market for primary care services in the Indian state of Bihar to understand how choice of primary care provider is influenced by distance, cost and quality of care. This study is based on linked surveys of rural households, PHCs, and private primary care providers conducted in 2019 and 2020. Most rural residents lived in proximity to a primary care provider, though not a qualified one. Within a 5-km distance, 60% of villages had a PHC, 90% had an informal provider, 35% an Indian systems of medicine practitioner, and 10% a private MBBS doctor. Most patients sought care from informal providers irrespective of PHC distance; only 25% of patients living in the PHC's vicinity sought care there. Reducing distance to the PHC by 1 km marginally increased the likehood of the PHC being selected, and reduced the likelihood of private clinics being selected. Reducing patient's costs at PHCs increased the likelihood of the PHC being selected and reduced the likelihood of private clinics and private hospitals being selected. Improved clinical quality at PHCs had no effect on patient selection of PHCs, private clinics, or hospitals. Illness severity reduced the likelihood of PHCs or private clinics being selected, and increased the likelihood of private hospitals selected. Wealthier patients were marginally more likely to use PHCs, substantially more likely to use private hospitals, and less likely to use private clinics. Expanding PHC network coverage or improving their quality of care is not sufficient to make PHCs more relevant to local health needs. An orientation towards essential public health functions, as well as, a community-centered approach to the organization of primary health care system is necessary.

Association of patient clinical and gut microbiota features with vancomycin-resistant enterococci environmental contamination in nursing homes: a retrospective observational study.

BACKGROUND: Preventing transmission is crucial for reducing infections with multidrug-resistant organisms (MDROs) in nursing homes. To identify resident characteristics associated with MDRO spread, we investigated associations between patient characteristics and contamination of their proximate room surfaces with vancomycin-resistant enterococci (VRE). METHODS: In this retrospective observational study, we used demographic and clinical data (including data on comorbidities, physical independence, catheter use within the past 30 days, and antibiotic exposure within the past 30 days) and surveillance cultures of patient body sites and room surfaces at enrolment and during weekly follow-up visits within the first month, and monthly thereafter (up to 6 months), in six US nursing homes collected in a previous clinical trial (September, 2016, to August, 2018). We did 16S rRNA gene sequencing on perirectal surveillance swabs to investigate the association between the gut microbiota and the culture status of participants and their rooms. FINDINGS: We included 245 participants (mean age 72·5 years [SD 13·6]; 111 [45%] were men, 134 [55%] were women, 132 [54%] were non-Hispanic white, and 112 [46%] were African American). We collected 2802 participant samples and 5592 environmental samples. At baseline, VRE colonisation was present in 49 (20%) participants, with environmental surfaces being contaminated in 36 (73%) of these patients. Hand contamination among VRE-colonised participants was more common in those with environmental contamination compared with those without (50 [51%] of 99 vs seven [13%] of 55; p<0·0001). We found a correlation between hand contamination and both groin and perirectal colonisation and contamination of various high-touch room surfaces (Cohen's κ 0·43). We found participant microbiota composition to be associated with antibiotic receipt within the past 30 days (high-risk antibiotics p=0·011 and low-risk antibiotics p=0·0004) and participant VRE colonisation status, but not environmental contamination among VRE-colonised participants (participant only vs uncolonised p=0·071, both participant and environment vs uncolonised p=0·025, and participant only vs participant and environment p=0·29). Multivariable analysis to identify independent factors associated with VRE-colonised participants contaminating their environment identified antibiotic exposure (adjusted odds ratio 2·75 [95% CI 1·22-6·16]) and male sex (2·75 [1·24-6·08]) as being associated with increased risk of environmental contamination, and physical dependence as being associated with a reduced risk of environmental contamination (0·91 [0·83-0·99]). INTERPRETATION: Our data support antibiotic use and interaction with proximal surfaces by physically independent nursing home residents as under-appreciated drivers of environmental contamination among VRE-colonised residents. Integrating resident hand-hygiene education and antimicrobial stewardship will strengthen efforts to reduce MDROs in nursing homes. FUNDING: US Centers for Disease Control and Prevention, National Institute of Health, Canadian Institutes of Health Research, and University of Michigan.

Understanding refugee and immigrant health literacy and beliefs toward antimicrobial resistance.

Refugee and migrant populations have increased vulnerability to antimicrobial resistance, yet stewardship guidance is lacking. We addressed this gap through a cross-sectional survey, finding that these populations and immigrants from low and middle-income countries had lower health literacy on the issue compared to native-born Americans and those from high-income countries.

Human Resources for Health in Haryana, India: What can be Done Better?

Introduction: Health systems in developing countries suffers from both input and productivity issues. We examined the status of three domains of human resources for health, i.e., availability and distribution, capacity and productivity, and motivation and job-satisfaction, of the health-care workforce employed in the public health system of Haryana, a North Indian state. Methodology: The primary data were collected from 377 public health facilities and 1749 healthcare providers across 21 districts. The secondary data were obtained from government reports in the public domain. Bivariate and multivariate statistical techniques were used for evaluating district performances, making inter-district comparisons and identifying determinants of motivation and job-satisfaction of the clinical cadres. Results: We found 3.6 core health-care workers (doctors, staff nurses, and auxiliary nurses-midwives) employed in the public health-care system per 10,000 population, ranging from 1.35 in Faridabad district to 6.57 in Panchkula district. Around 78% of the sanctioned positions were occupied. A number of inpatient hospitalizations per doctor/nurses per month were 17 at the community health center level and 29 at the district hospital level; however, significant differences were observed among districts. Motivation levels of community health workers (85%) were higher than clinical workforce (78%), while health system administrators had lowest motivation and job satisfaction levels. Posting at primary healthcare facility, contractual employment, and co-habitation with family at the place of posting were found to be the significant motivating factors. Conclusions: A revamp of governance strategies is required to improve health-care worker availability and equitable distribution in the public health system to address the observed geographic variations. Efforts are also needed to improve the motivation levels of health system administrators, especially in poorly performing districts and reduce the wide gap with better-off districts.

Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit.

Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States. Current prevention strategies are limited by their failure to account for patients who carry C. difficile asymptomatically, who may act as hidden reservoirs transmitting infections to other patients. To improve the understanding of asymptomatic carriers' contribution to C. difficile spread, we conducted admission and daily longitudinal culture-based screening for C. difficile in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic C. difficile detected in at least one sample, only 1% of patients culturing negative on admission to the unit acquired C. difficile via cross-transmission. While patients who carried toxigenic C. difficile on admission posed minimal risk to others, they themselves had a 24-times greater risk for developing a healthcare-onset C. difficile infection than noncarriers. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C. difficile, and that decreasing C. difficile infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection.

Regional changes in intestinal permeability in cirrhosis are associated with mucosal bacteria.

BACKGROUND: Several complications of cirrhosis are theorized to result from the translocation of bacteria or their products across the intestinal epithelium. We aimed to assess epithelial permeability and associations with mucosal bacteria in patients with cirrhosis. APPROACH AND RESULTS: We collected 247 duodenum, ileum, and colon biopsies from 58 consecutive patients with cirrhosis and 33 controls during clinically indicated endoscopies. Patients with cirrhosis were similarly aged to controls (60 vs. 58 y) and had a median Model for End-stage Liver Disease of 8 (interquartile range 7, 10). Biopsies underwent 16S rRNA-encoding gene amplicon sequencing to determine mucosal bacteria composition and transepithelial electrical resistance (TEER) to determine epithelial permeability. In the entire cohort, there were regional differences in TEER with the lowest TEER (ie, more permeable) in the ileum; duodenum TEER was 43% higher and colon TEER 20% higher than ileum TEER (ANOVA p = 0.0004). When comparing patients with cirrhosis and controls, both TEER (26% lower in cirrhosis, p = 0.006) and alpha diversity differed in the duodenum (27% lower in cirrhosis, p = 0.01) but not ileum or colon. A beta-binomial model found that 26 bacteria were significantly associated with TEER. Bifidobacteriaceae Bifidobacterium in duodenal mucosa was protective of epithelial permeability and future hospitalization for hepatic decompensation. CONCLUSIONS: Duodenal epithelial permeability was higher, and mucosal bacteria alpha diversity was lower in cirrhosis compared to controls, while no such differences were seen in the ileum or colon. Specific bacteria were associated with epithelial permeability and future hepatic decompensation.

Key patient demographics shape innate immune topography in noncritical hypoxic COVID-19 pneumonia.

Risk of severe disease and death due to COVID-19 is increased in certain patient demographic groups, including those of advanced age, male sex, and obese body mass index. Investigations of the biological variations that contribute to this risk have been hampered by heterogeneous severity, with immunologic features of critical disease potentially obscuring differences between risk groups. To examine immune heterogeneity related to demographic risk factors, we enrolled 38 patients hospitalized with clinically homogeneous COVID-19 pneumonia - defined as oxygen saturation less than 94% on room air without respiratory failure, septic shock, or multiple organ dysfunction - and performed single-cell RNA-Seq of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte/dendritic cell (Mo/DC) compartments, revealing altered immune cell type-specific responses in higher risk COVID-19 patient subgroups. Specifically, we found transcriptional evidence of altered neutrophil maturation in aged versus young patients and enhanced cytokine responses in Mo/DCs of male versus female patients. Such innate immune cell alterations may contribute to outcome differences linked to these risk factors. They also highlight the importance of diverse patient cohorts in studies of therapies targeting the immune response in COVID-19.