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Saif Mashaqi,1,2 Daniel Laubitz,3 Efreim Joseph D Morales,3 Richard De Armond,1,2 Hanan Alameddin,4 Fayez K Ghishan,3 Pawel R Kiela,3,5 Sairam Parthasarathy1,2 1Department of Pulmonary, Allergy, Critical Care, and Sleep, University of Arizona College of Medicine, Tucson, AZ, USA; 2University of Arizona Health Sciences Center for Sleep & Circadian Sciences, University of Arizona College of Medicine, Tucson, AZ, USA; 3Department of Pediatrics, Steele Children’s Research Center, University of Arizona College of Medicine, Tucson, AZ, USA; 4The University of Arizona College of Pharmacy, Tucson, AZ, USA; 5Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USACorrespondence: Saif Mashaqi, Department of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The University of Arizona, College of Medicine Tucson, 1625 N Campbell Ave, Tucson, AZ, 85719, USA, Tel +1 520-626-8309, Fax +1 520-626-1876, Email saifmashaqi@email.arizona.eduPurpose: Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and sustained hypoxia (IH+SH) (characterizing obesity hypoventilation syndrome) and HFD on gut dysbiosis is unclear. We aimed to investigate the interactive effect of a combination of IH and SH and HFD on proximal colonic microbiota and colonic gene expression pattern.Methods: Male mice (n=16) were randomly received four different combinations of diet (normal versus HFD) and oxygen conditions (normoxia versus IH+SH) for 4 weeks. Bacterial DNA and mucosal epithelial cell RNA from proximal colon were collected for analysis of adherent microbiome and host’s gene expression analysis.Results: HFD during IH+SH (22.6 ± 5.73; SD) led to greater Firmicutes: Bacteroidetes ratio than HFD during normoxia (5.89 ± 1.19; p=0.029). HFD significantly decreased microbial diversity as compared to normal diet, but the addition of IH+SH to HFD mildly reversed such effects. When compared to HFD during normoxia, HFD with combination of IH+SH resulted in changes to host mucosal gene expression for apical junctional complexes and adhesion molecules. Specifically, when compared to HFD during normoxia, HFD during IH+SH led to upregulation of Claudin 2 and Syk (tight junction dysfunction and increased mucosal permeability), while the barrier promoting claudin 4 was downregulated.Conclusion: HFD during combined IH and SH causes greater gut dysbiosis and potentially adverse changes in colonic epithelial transcriptome than HFD during normoxia. The latter changes are suggestive of impaired gut barrier function.Keywords: hypoxia, microbiome, obesity, diet, gene expression, sleep apnea

Background: The association between the administration of sodium-glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known., Methods: This retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30-90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed., Results: From 2021 to 2023, 374 patients were included in the study-316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45-2.56]) or with MAKE30-90 (OR 0.76 [0.42-1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01-0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM ( p ≤ 0.05 for all)., Conclusion: The use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alcantar-Vallin, Zaragoza, Díaz-Villavicencio, Hernandez-Morales, Camacho-Guerrero, Perez-Venegas, Carmona-Morales, Oseguera-Gonzalez, Murguia-Soto, Chávez-Alonso, Arredondo-Dubois, Orozco-Chan, Gómez-Fregoso, Rodríguez-García, Navarro-Blackaller, Medina-González, Martínez Gallardo-González, Abundis-Mora, Vega-Vega, García-García and Chávez-Iñiguez.)

This study aims to evaluate the effect of a mental health Narrative Community-Based Group Therapy (NCGT) in Afro-Colombian violence survivors. A randomized controlled trial was conducted in Buenaventura and Quibdó, Colombia. Afro-Colombian adults ( n =521) were randomly allocated to a NCGT (n 1 =175), a wait-control group (n 2 =171) or a Common Elements Treatment Approach (CETA, n 3 =175). The CETA was described separately given conceptual/methodological differences. Lay psychosocial community workers delivered the NCGT. Symptoms were assessed before and after intervention/wait with culturally adapted mental health symptoms and gender-specific functionality scales. Intent to treat analysis and mean difference of differences were used for comparisons. In Buenaventura, a significant reduction in functional impairment (mean difference: -0.30, 95% Confidence Interval [95% CI]: -0.55, -0.05) and depression (mean difference: -0.24, 95% CI: -0.42, -0.07) were found, with small and moderate effect size, respectively. In Quibdó, functionality improved significantly (mean difference: -0.29, 95% CI: -0.54, -0.04, small effect size). Even though differences in depression and anxiety were not significant, there were reductions in symptoms. The NCGT is effective in improving daily functioning among violence victims in the Colombian Pacific and has the potential to reduce symptoms of depression. Further exploration is required to understand the effects of a narrative group therapy for mental health in Afro-Colombian populations. Trial Registration: ClinicalTrials.gov number: NCT01856673 (https://clinicaltrials.gov/ct2/show/NCT01856673).

Introduction: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia., Methods: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication., Results: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions., Conclusion: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment., (© 2023 S. Karger AG, Basel.)

Background: Exposure to violence has negative consequences on mental health. Armed-conflict in Colombia has widely affected Afro-descendants in the Pacific region. Evidence regarding effectiveness of mental health interventions is lacking in low-income settings, especially in areas with active conflict. The objective of this study is to evaluate an individualized Common Elements Treatment Approach (CETA), a transdiagnostic psychotherapy model based on Cognitive-Behavioral Therapy, for adult trauma survivors., Methods and Findings: A referred sample of 521 adult Afro-descendants from Buenaventura and Quibdó, Colombia, experiencing significant sadness, suffering or fear (score>0.77 in Total Mental Health Symptoms), with history of traumatic experiences, and with associated functional impairment were randomly allocated to CETA intervention, standby group without intervention, but under monthly monitoring, or a Narrative Community-Based Group Therapy. CETA was provided by trained Lay Psychosocial Community Workers without previous mental health experience, supervised by psychologists, during 12-14 weekly, 1.5-hour sessions. Symptoms were assessed with a locally validated survey built based on the Hopkins Symptom Checklist, the Harvard Trauma Questionnaire, the PTSD CheckList-Civilian Version, a qualitative study for additional general symptoms and a gender-specific functional impairment scale. CETA was compared with the control group and the intervention effects were calculated with mixed models using intention to treat analysis. Participant completion of follow-up was 75.1% and 13.2% voluntarily withdrew. Reduction in post-traumatic stress symptoms was significant in both municipalities when comparing intervention and control groups (mean difference), with a with a moderate effect size in Buenaventura (Cohen's d  =  0.70) and a small effect size in Quibdó (d = 0.31). In Buenaventura, the intervention also had significant effects on depression (large effect size d = 1.03), anxiety (large effect size d = 0.80) and functional impairment (moderate effect size d = 0.70). In Quibdó, it had no significant effect on these outcomes. Changes in Total Mental Health Symptoms were not significant in neither city., Conclusions: This trial suggests that CETA, can be effective in improving depression, anxiety, post-traumatic stress and function among victims of systematized violence in low-income and active conflict settings. Nonetheless, the difference of effectiveness between the two cities of intervention may indicate that we cannot assume that a mental health intervention known to be effective in one setting will be effective in another, even in similar circumstances and population. This may have special importance when implementing and reproducing these types of intervention in non-controlled circumstances. Further research should address these concerns. Results can be of use by governmental decision-makers when defining mental health programs for survivors., Trial Registration: ClinicalTrials.gov NCT01856673 (https://clinicaltrials.gov/ct2/show/NCT01856673)., Competing Interests: The authors have declared that no competing interests exist.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4 + T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8 + T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3 -/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA., (© 2017 Daley et al.)

The aim of this article is to verify the influence of tuberculosis on mass tourism architecture. To achieve this, the paper analyses the typological evolution of the hotel since the middle of the nineteenth century, when the first sanatoria appeared in the alpine resorts. A study that creates links between the progress in architecture and the medical therapy advances. The goal is to highlight the hybridisation process between both architectural typologies. Although this overlapping is developed until the Second World War, the influence of its mixture is still present in contemporary mass tourism architecture.

Prior studies have indicated that MJ1099 from Methanocaldococcus jannaschii has roles in the biosynthesis of tetrahydromethanopterin and methanofuran, two key cofactors of one-carbon (C1) metabolism in diverse organisms including the methanogenic archaea. Here, the structure of MJ1099 has been solved to 1.7 Å resolution using anomalous scattering methods. The results indicate that MJ1099 is a member of the TIM-barrel superfamily and that it is a homohexamer. Bioinformatic analyses identified a potential active site that is highly conserved among MJ1099 homologs and the key amino acids involved were identified. The results presented here should guide further studies of MJ1099 including mechanistic studies and possibly the development of inhibitors that target the methanogenic archaea in the digestive tracts of humans and that are a source of the greenhouse gas methane.

Objective: To determine a) if the admission osmole gap, the difference between osmolality and osmolarity, is the same in the neurologic-neurosurgical intensive care unit (NNICU) population as in healthy controls; b) which of 11 osmole gap formulas, or osmolality, correlates best with mannitol serum concentrations; c) whether osmole gap correction for plasma water content improves this correlation; and d) whether the osmole gap can predict mannitol serum concentrations., Design: Prospectively collected data., Settings: NNICU of a tertiary teaching hospital., Subjects: Ten NNICU patients on mannitol and eight not on mannitol, and 95 healthy controls., Interventions: None., Measurements and Main Results: We compared the admission osmole gap between all 18 NNICU patients and healthy controls and the correlation between osmole gap or osmolality and mannitol serum concentrations in ten NNICU patients while receiving mannitol. The osmole gap was calculated using 11 osmolarity formulas (six corrected for plasma water content). Student's t-test was used to compare the mean osmole gap between control and patient groups.We found that the mean osmole gap in healthy subjects and NNICU patients was not different. There were no statistically significant differences between any of the 11 osmole gap formulas and the correlation of osmole gap with serum mannitol concentrations; the highest R =.80, with formula 4, 1.86 (sodium + potassium) + (blood urea nitrogen/2.8) + (glucose/18) + 10, requires the least laboratory measurements. Osmolality had the lowest correlation with mannitol concentration (R =.60), significantly lower than any of the osmole gap calculations. Plasma water content correction did not improve this correlation. The osmole gap-mannitol serum concentrations relationship is 1 to 0.81, not accurate enough to predict specific mannitol serum concentrations., Conclusions: The osmole gap correlates better with mannitol serum concentrations than osmolality, and although it cannot predict a specific mannitol serum concentration, a normal osmole gap concentration, as we find at trough times, indicates sufficient clearance for a new mannitol dose.