Influence of Temperature and Precipitation on the Effectiveness of Water, Sanitation, and Handwashing Interventions against Childhood Diarrheal Disease in Rural Bangladesh: A Reanalysis of the WASH Benefits Bangladesh Trial.

BACKGROUND: Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions. OBJECTIVES: We aimed to determine whether temperature and precipitation modified the effect of low-cost, point-of-use WASH interventions on child diarrhea. METHODS: We analyzed data from a trial in rural Bangladesh that compared child diarrhea prevalence between clusters (N=720) that were randomized to different WASH interventions between 2012 and 2016 (NCT01590095). We matched temperature and precipitation measurements to diarrhea outcomes (N=12,440 measurements, 6,921 children) by geographic coordinates and date. We estimated prevalence ratios (PRs) using generative additive models and targeted maximum likelihood estimation to assess the effectiveness of each WASH intervention under different weather conditions. RESULTS: Generally, WASH interventions most effectively prevented diarrhea during monsoon season, particularly following weeks with heavy rain or high temperatures. The PR for diarrhea in the WASH interventions group compared with the control group was 0.49 (95% CI: 0.35, 0.68) after 1 d of heavy rainfall, with a less-protective effect [PR=0.87 (95% CI: 0.60, 1.25)] when there were no days with heavy rainfall. Similarly, the PR for diarrhea in the WASH intervention group compared with the control group was 0.60 (95% CI: 0.48, 0.75) following above-median temperatures vs. 0.91 (95% CI: 0.61, 1.35) following below-median temperatures. The influence of precipitation and temperature varied by intervention type; for precipitation, the largest differences in effectiveness were for the sanitation and combined WASH interventions. DISCUSSION: WASH intervention effectiveness was strongly influenced by precipitation and temperature, and nearly all protective effects were observed during the rainy season. Future implementation of these interventions should consider local environmental conditions to maximize effectiveness, including targeted efforts to maintain latrines and promote community adoption ahead of monsoon seasons. https://doi.org/10.1289/EHP13807.

Understanding the Impact of Contemporary Racism on the Mental Health of Middle Class Black Americans.

Evidence from previous research indicates that while socioeconomic status (SES) narrows Black-White health inequities, these inequities do not completely disappear, and in some cases, worsen. Why do Black-White health inequities persist, even when controlling for SES? It is critical to examine how perceptions of unfair treatment, especially those that are nuanced and subtle, affect the mental health of Black Americans with greater levels of SES. This study, using a new sample composed exclusively of college-educated Black Americans, investigated whether experiences related to racism were associated with poorer mental health. Qualtrics provided the sample from their nationwide panelists that met the research criteria. Inclusion criteria included the following: (1) self-identified as Black or African American; (2) at least 24 years old; (3) completed a 4-year college degree or higher. The findings from this study indicated that the effects of unfair treatment are significantly associated with poorer mental health. These findings highlight the insidious nature of contemporary racism as the everyday experiences of unfair treatment have a tremendous effect on depressive symptoms among this sample of college-educated Black Americans. Efforts to simply improve SES among historically marginalized groups will not bring about health equity. Findings from this study indicate that there are mental health costs associated with upward social mobility. It is likely that these costs, particularly the experience of everyday unfair treatment, likely diminish the social, economic and health returns on the human capital.

Intersectionality and Mental Health Among Emerging Adult Black American Men: a Scoping Review.

PURPOSE OF REVIEW: We conducted a scoping review to evaluate the degree to which literature published within the past 5 years concerning mental health among Black emerging adult men in the USA engaged with intersectionality. METHODS: Using scoping review methods, we applied the following a-priori eligibility criteria: (i) sample included Black/African American men who were aged 18-29 years, (ii) pertained to general mental wellness, depression, or anxiety, (iii) published within between 2017 and 2022, (iv) empirical and/or theoretical literature including reviews, pre-prints, and reports from organizations or professional groups, (v) conducted in the USA. In total, 1384 studies were identified from the databases, after which 224 duplicates were removed, resulting in 1160 unique citations that were screened in the title/abstract phase. Overall, 376 sources were assessed for full-text eligibility, and 20 studies were included for extraction. Information pertaining to sample characteristics, intersectionality, and main mental health results were extracted from the included studies. RECENT FINDINGS: Findings from this review indicate that there is a paucity of research that has investigated the mental health of Black American, emerging adult men. Of the studies that have been conducted in recent years, there are few that have used an intersectional framework to examine how different social identities intersect to affect mental health. This review underscores that the mental health of emerging adult Black men is of considerable concern given the developmental stage, social and historical context as well as intersecting identities that men in this stage embody.

Glucagon-Like Peptide 1-Based Therapies and Risk of Pancreatic Cancer in Patients With Diabetes and Obesity.

OBJECTIVES: There have been conflicting reports concerning an increased risk of pancreatic cancer (PC) in new users of glucagon-like peptide-1 agonists (GLP-1As). We aimed to explore whether the use of GLP-1A is associated with an increased risk of PC. METHODS: A multicenter, retrospective cohort study was conducted using TriNetX. Adult patients with diabetes and/or overweight and obesity who were newly treated with GLP-1A or metformin for the first time between 2006 and 2021 were matched 1:1 using propensity score matching. The risk of PC was estimated using a Cox proportional hazards model. RESULTS: A total of 492,760 patients were identified in the GLP-1A and 918,711 patients in the metformin group. After propensity score matching, both cohorts (370,490 each) were well matched. During follow-up, 351 patients in the GLP-1A and 956 on metformin developed PC after an exposure lag of 1 year. Glucagon-like peptide-1 agonists was associated with a significantly lower risk of PC (hazard ratio, 0.47; 95% confidence interval, 0.42-0.52). CONCLUSIONS: The use of GLP-1A in patients with obesity/diabetes is associated with a lower risk of PC compared with a similar cohort of patients using metformin. Our study findings reassure clinicians and patients with apprehensions about any possible association between GLP-1A and PC.

Impact of COVID-19 on interest in hepato-pancreato-biliary diseases.

An important gap of knowledge exists regarding the public interest in hepato-pancreato-biliary (HPB) diseases during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the public interest in HPB diseases in the COVID-19 era. In this infodemiology study, we performed a comparative analysis of Google search volume of HPB terms in 2020-2021 and compared it to a similar time frame (2016-2019) in 3 periods to assess how trends in patient seeking behavior of HPB terms changed during the course of the pandemic in the USA and worldwide. Our analysis showed a substantial decrease in search volume of HPB diseases and procedure terms early in the pandemic. However, search volumes appeared to revert back to pre-pandemic years closer to the 1-year mark in USA and worldwide. Patients may have initially neglected HPB-related issues during the early phase of the COVID-19 pandemic, which could lead to worse outcomes. While HPB-related terms reverted closer to pre-pandemic levels later in the pandemic, further research is needed to assess the long-term impacts.

Immune Checkpoint Inhibitors Induced Hepatotoxicity; Gastroenterologists' Perspectives.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have promising clinical activity and are essential medications for patients with several malignancies. However, by deranging the immune system, these novel agents could lead to immune-related adverse events (IRAEs). Hepatotoxicity with checkpoint inhibitors usually results in acute hepatitis or drug-induced liver injury. METHODS: This review article discusses the recent clinical evidence available regarding checkpoint inhibitor-induced hepatitis and reviews an approach to their diagnosis and management. CONCLUSION: ICIs have improved patients' outcomes with different forms of malignancy; however, ICIs-related liver damage is a clinically significant entity in these patients. All patients should be monitored carefully for IRAEs while undergoing treatment with ICIs.

Transplant Hepatectomy With Portacaval Shunt and MARS Therapy for Perioperative Catastrophe: A Series of Four Liver Transplant Cases.

Increased worldwide focus on maximal donor utilization and transplantation of patients once considered too ill to survive liver transplantation may increase the otherwise rare frequency of catastrophic graft failure. Although the deleterious effects of an acutely failing allograft have been established for decades, the optimal strategy in this patient population in the perioperative period remains ill-defined. METHODS: A retrospective review of all liver transplant recipients with perioperative failure leading to transplant hepatectomy between January 1, 2014 and June 30, 2017 was performed. All patients were supported with MARS therapy while awaiting retransplantation. RESULTS: Four patients experienced catastrophic graft failure from massive exsanguination and liver fracture (1), portal vein and hepatic artery thrombosis (1), idiopathic necrosis (1), and necrosis from inadequate donor flushing/primary nonfunction (1). All patients improved following transplant hepatectomy with portacaval shunting. Patients were supported with intubation, vasopressors, renal replacement therapy, and Molecular Adsorbent Recirculating System therapy. All patients underwent retransplantation after a mean anhepatic phase of 48.8 (± 5.13) h. Survival to discharge was 75%. CONCLUSIONS: Although catastrophic liver failure is highly challenging, acceptable outcomes can be achieved with timely hepatectomy with portacaval shunt and retransplantation, particularly in patients supported with the Molecular Adsorbent Recirculating System device.

Temporal Trends and Predictors of Pancreatitis Patients Who Leave Against Medical Advice: A Nationwide Analysis.

BACKGROUND: Acute pancreatitis is the leading gastrointestinal cause of hospital admissions. Our study aims to determine the trends and predictors of discharge against medical advice (AMA). METHODS: We utilized the Nationwide Inpatient Sample (2003 - 2016) to identify patients admitted with pancreatitis. We compared in-hospital complications and determined predictors of discharge AMA using a multivariate logistic regression. RESULTS: A total of 7,158,894 patients were admitted with pancreatitis. Of those, 199,351 left AMA. Discharge AMA increased over time from 2.3% to 3.2%. Patients who left AMA were more likely to be younger, male, black, and a lower socioeconomic status (SES). They had a greater prevalence of depression, cirrhosis, smoking, drug abuse, and human immunodeficiency virus (HIV) infection. Alcohol use was the most likely etiology of pancreatitis among those leaving AMA. In a multivariate regression, patients more likely to leave AMA included: age 18 - 44, male, and black. Patients with a history of depression, drug abuse, and HIV infection were also more likely to be discharged AMA. CONCLUSIONS: Discharges AMA increased over time. Predictors of AMA include patients who are younger, male, black, lower socioeconomic status, and have a history of depression, HIV infection, alcohol and drug use. Future studies are necessary to examine the reasons for discharge AMA among this population.

Coherences of Bacteriochlorophyll a Uncovered Using 3D-Electronic Spectroscopy.

Mapping the multidimensional energy landscape of photosynthetic systems is crucial for understanding their high efficiencies. Multidimensional coherent spectroscopy is well suited to this task but has difficulty distinguishing between vibrational and electronic degrees of freedom. In pigment-protein complexes, energy differences between vibrations within a single electronic manifold are similar to differences between electronic states, leading to ambiguous assignments of spectral features and diverging physical interpretations. An important control experiment is that of the pigment monomer, but previous attempts using multidimensional coherent spectroscopy lacked the sensitivity to capture the relevant spectroscopic signatures. Here we apply a variety of methods to rapidly acquire 3D electronic-vibrational spectra in seconds, leading to a mapping of the vibrational states of Bacteriochlorophyll a (BChl a) in solution. Using this information, we can distinguish features of proteins containing BChl a from the monomer subunit and show that many of the previously reported contentious spectral signatures are vibrations of individual pigments.

Exciton-Phonon Spectroscopy of Quantum Dots Below the Single-Particle Homogeneous Line Width.

We demonstrate that high-dimensionality coherent spectroscopy yields "super-resolved" spectra whereby peaks may be localized far below their homogeneous line width by resolving them across multiple, coherently coupled dimensions. We implement this technique using a fifth-order photon-echo spectroscopy called Gradient-Assisted Multidimensional Electronic-Raman Spectroscopy (GAMERS) that combines resonant and nonresonant excitation to disperse the optical response across three spectral dimensions: two involving excitonic transitions and one that encodes phonon energies. In analogy to super-resolution localization microscopies, which separate spatially overlapping signals in time, GAMERS isolates signals spectrally using combined electronic and nuclear resolution. Optical phonon lines in a colloidal solution of CdSe quantum dots at room temperature separated by less than 150 µeV are resolved despite the homogeneous line width of these transitions being nearly an order of magnitude broader. The frequency difference between these phonon modes is attributed to softening of the longitudinal phonon mode upon excitation to the lowest exciton state. Further, such phonon mode selectivity yields spectra with electronic line widths that approach the single particle limit. Through this enhanced spectral resolution, the GAMERS method yields insights into the nature of coupling between longitudinal optical and acoustic phonons and specific excitonic transitions that were previously hidden.

Ultrafast Four-Dimensional Coherent Spectroscopy by Projection Reconstruction.

Multidimensional coherent spectroscopy provides insights into the vibronic structure and dynamics of complex systems. In general, the higher the dimensionality, the better the spectral discrimination and the more information that may be extracted about the system. A major impediment to widespread implementation of these methods, however, is that the acquisition time generally increases exponentially with dimensionality, prohibiting practical implementation. We demonstrate the use of nonuniform sampling based on the projection-slice theorem and inverse Radon transform within the context of a fifth-order, 4D technique (GAMERS) designed to correlate the vibrational contributions to different electronic states. Projection-reconstruction (PRO GAMERS) greatly reduces the data sampling requirements without sacrificing frequency resolution. The sensitivity of this technique is demonstrated to surpass conventional uniform sampling by orders of magnitude. The incorporation of projection-reconstruction into multidimensional coherent spectroscopy opens up the possibility to study the structure of complex chemical, biological, and physical systems with unprecedented detail.

Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis.

The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultrahigh performance liquid chromatography-tandem mass spectrometry to identify preliminary metabolomic biomarker candidates. Among the 1028 metabolites identified, 34 were significantly increased in subjects with high liver and kidney disease severity compared with those with low liver and kidney disease severity. The highest average fold-change (2.39) was for 4-acetamidobutanoate. Metabolite-based enriched pathways were significantly associated with the identified metabolomic signature (P values ranged from 2.07E-06 to 0.02919). Ascorbate and aldarate metabolism, methylation, and glucuronidation were among the most significant protein-based enriched pathways associated with this metabolomic signature (P values ranged from 1.09E-18 to 7.61E-05). Erythronate had the highest association with measured GFR (R-square = 0.571, P <0.0001). Erythronate (R = 0.594, P <0.0001) and N6-carbamoylthreonyladenosine (R = 0.591, P <0.0001) showed stronger associations with measured GFR compared with creatinine (R = 0.588, P <0.0001) even after controlling for age, gender, and race. The 5 most significant metabolites that predicted mortality independent of kidney disease and demographics were S-adenosylhomocysteine (P = 0.0003), glucuronate (P = 0.0006), trans-aconitate (P = 0.0018), 3-ureidopropionate (P = 0.0021), and 3-(4-hydroxyphenyl)lactate (P = 0.0047). A unique metabolomic signature associated with hepatorenal dysfunction in cirrhosis was identified for further investigations that provide potentially important mechanistic insights into cirrhosis-altered metabolism.

Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

BACKGROUND DATA: Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. METHODS: MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. RESULTS: Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. CONCLUSIONS: MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS: The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Quantum coherence selective 2D Raman-2D electronic spectroscopy.

Electronic and vibrational correlations report on the dynamics and structure of molecular species, yet revealing these correlations experimentally has proved extremely challenging. Here, we demonstrate a method that probes correlations between states within the vibrational and electronic manifold with quantum coherence selectivity. Specifically, we measure a fully coherent four-dimensional spectrum which simultaneously encodes vibrational-vibrational, electronic-vibrational and electronic-electronic interactions. By combining near-impulsive resonant and non-resonant excitation, the desired fifth-order signal of a complex organic molecule in solution is measured free of unwanted lower-order contamination. A critical feature of this method is electronic and vibrational frequency resolution, enabling isolation and assignment of individual quantum coherence pathways. The vibronic structure of the system is then revealed within an otherwise broad and featureless 2D electronic spectrum. This method is suited for studying elusive quantum effects in which electronic transitions strongly couple to phonons and vibrations, such as energy transfer in photosynthetic pigment-protein complexes.

Isolated Ground-State Vibrational Coherence Measured by Fifth-Order Single-Shot Two-Dimensional Electronic Spectroscopy.

Vibrations play a critical role in many photochemical and photophysical processes in which excitations reside on the electronically excited state. However, difficulty in assigning signals from spectroscopic measurements uniquely to a specific electronic state, ground or otherwise, has exposed limitations to their physical interpretation. Here, we demonstrate the selective excitation of vibrational coherences on the ground electronic state through impulsive Raman scattering, whose weak fifth-order signal is resonantly enhanced by coupling to strong electronic transitions. The six-wave mixing signals measured using this technique are free of lower-order cascades and represent correlations between zero-quantum vibrational coherences in the ground state and single-quantum coherences between the ground and electronic states. We believe that this technique has the potential to shed much-needed insight onto some of the mysteries regarding the origin of long-lived coherences observed in photosynthetic and other coupled chromophore systems.

Sequential kidney-liver transplantation from the same living donor for lecithin cholesterol acyl transferase deficiency.

BACKGROUND: Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease (ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency. METHODS: A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). One year following the kidney transplant, auxiliary partial orthotopic liver transplant (APOLT) of a left lateral segment from the same donor was performed. RESULTS: At 5 years follow-up, there have been no major complications, readmissions, or rejection episodes. Serum lipid abnormalities recurred within the first year, but liver and kidney allograft function remains intact. CONCLUSION: Few cases of sequential transplantation from the same LD have been performed in adults. This is the first APOLT and multi-organ transplant performed for LCAT deficiency. Sequential organ transplant from the same LD for ESRD secondary to a metabolic disorder of the liver is feasible in adults and should be further investigated.

Estimation of Glomerular Filtration Rate in Patients With Cirrhosis by Using New and Conventional Filtration Markers and Dimethylarginines.

BACKGROUND & AIMS: Equations used to estimate glomerular filtration rate (GFR) are not accurate in patients with cirrhosis. We aimed to develop a new equation to estimate the GFR in subjects with cirrhosis and compare its performance with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C and creatinine-cystatin C equations, which were derived in populations without cirrhosis. METHODS: From 2010 through 2014, we measured GFR in 103 subjects with cirrhosis based on non-radiolabeled iothalamate plasma clearance. We measured blood levels of creatinine, cystatin C, ß-trace protein, ß2-microglobulin, L-arginine, and symmetric and asymmetric dimethylarginines simultaneously with GFR. Multivariate linear regression analysis was performed to develop models to estimate GFR. Overall accuracy, defined by the root mean square error (RMSE) of our newly developed model to estimate GFR, was compared with that of the CKD-EPI equations. To obtain an unbiased estimate of our new equation to estimate GFR, we used a leave-one-out cross-validation strategy. RESULTS: After we considered all the candidate variables and blood markers of GFR, the most accurate equation we identified to estimate GFR included serum levels of creatinine and cystatin C, as well as patients' age, sex, and race. Overall, the accuracy of this equation (RMSE = 22.92) was superior to that of the CKD-EPI cystatin C equation (RMSE = 27.27, P = .004). Among subjects with cirrhosis and diuretic-refractory ascites, the accuracy of the equation we developed to estimate GFR (RMSE = 19.36) was greater than that of the CKD-EPI cystatin C (RMSE = 27.30, P = .003) and CKD-EPI creatinine-cystatin C equations (RMSE = 23.37, P = .004). CONCLUSIONS: We developed an equation that estimates GFR in subjects with cirrhosis and diuretic-refractory ascites with greater accuracy than the CKD-EPI cystatin C equation or CKD-EPI creatinine-cystatin C equation.