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AIM: Many countries risk failing the Sustainable Development Goal to reduce neonatal mortality to 12 in 1000 live births before 2030, necessitating intervention. This scoping review assesses available evidence from studies implementing smartphone application-based education and clinical decision support in neonatal emergency care in low- and middle-income countries and describes applied assessment tools to highlight gaps in the current literature. METHODS: A systematic search on 28 March 2024 of PubMed, Web of Science, and EMBASE identified original research papers published in peer-reviewed journals after 2014 in English. The evaluation was based on Kirkpatrick's framework. RESULTS: In total, 20 studies assessing eight different smartphone applications were included. Participants found applications acceptable and feasible in 11 of 14 studies. Knowledge and/or skills were improved in 11 of 12 studies. Behaviour was assessed in 10 studies by tracking app usage. Patient outcome was assessed in four studies, focusing on perinatal mortality, Basic Newborn Care outcomes and correct assessment of newborns. CONCLUSION: Data from included studies further strengthens hope that smartphone applications can improve neonatal mortality rates in low- and middle-income countries. However, further research into the effectiveness of these applications is warranted. This review highlights gaps in the current literature and provides guidance for future trials.

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OBJECTIVES: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs. MATERIALS AND METHODS: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. RESULTS: The mean and standard deviation of TSC and long-component 23Na T2* values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava. DISCUSSION: Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23Na T2* values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects.

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El virus de inmunodeficiencia humana constituye uno de los principales problemas de salud a nivel mundial. Se reconoce como un fenómeno multifactorial, donde las políticas públicas en materia de prevención, diagnóstico oportuno y tratamiento resultan claves. El objetivo del presente estudio es describir los avances en políticas públicas y vigilancia epidemiológica relacionadas con el virus de inmunodeficiencia humana/sida en Ecuador. Se evidencian importantes pasos con respecto al compromiso político y responsabilidad social para conseguir frenar los estragos del virus de inmunodeficiencia humana/sida, e infecciones de transmisión sexual, a partir de estrategias centradas en la prevención, así como en el tratamiento profiláctico, antirretroviral, y el seguimiento de los pacientes. Con vistas a ello se han implementado proyectos destinados a cumplir lo acordado en la declaración de las Naciones Unidas, y en el marco del plan nacional para el desarrollo. Persisten dificultades relacionadas con el acceso al diagnóstico del virus y pruebas de seguimiento, principalmente por la concentración de estas en una única institución.

The human immunodeficiency virus is one of the main health problems worldwide. It is recognized as a multifactorial phenomenon, where public policies regarding prevention, timely diagnosis and treatment are key. The objective of this study is to describe the advances in public policies and epidemiological surveillance related to the human immunodeficiency virus/AIDS in Ecuador. Important steps are evident in relation to political commitment and social responsibility to stop the injuries of the human immunodeficiency virus/AIDS, and sexually transmitted infections, based on strategies focused on prevention, as well as prophylactic, antiretroviral, and treatment patient follow-up. Some projects have been implemented aimed at fulfilling what was agreed in the United Nations declaration, and within the framework of the national development plan. Difficulties persist related to access to virus diagnosis and follow-up tests, mainly due to the concentration of these in a single institution.

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The disproportionate number of COVID-19 cases and deaths in the United States (US) requires understanding of health behaviors that contributed to low acceptance of public health guidelines. University students were at low risk for complications from COVID-19 infections but at high-risk for infecting others. It is important to understand which characteristics influenced willingness to receive the COVID-19 vaccine. The purpose of this cross-sectional study was to explore the social factors and identities that predicted university students' willingness to receive COVID-19 vaccines before one was available. This study used a stratified random sample from a Midwestern public university in 2020 (N = 614). Results suggest hesitancy toward childhood vaccinations, noncompliance with mask-wearing and large-group-avoidance guidelines, and conservative political ideology increased the odds of being unwilling to receive a COVID-19 vaccination. However, higher subjective social status and male gender increased the odds of being willing to be vaccinated.

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Current mitochondrial DNA (mtDNA) haplogroup classification tools map reads to a single reference genome and perform inference based on the detected mutations to this reference. This approach biases haplogroup assignments towards the reference and prohibits accurate calculations of the uncertainty in assignment. We present HaploCart, a probabilistic mtDNA haplogroup classifier which uses a pangenomic reference graph framework together with principles of Bayesian inference. We demonstrate that our approach significantly outperforms available tools by being more robust to lower coverage or incomplete consensus sequences and producing phylogenetically-aware confidence scores that are unbiased towards any haplogroup. HaploCart is available both as a command-line tool and through a user-friendly web interface. The C++ program accepts as input consensus FASTA, FASTQ, or GAM files, and outputs a text file with the haplogroup assignments of the samples along with the level of confidence in the assignments. Our work considerably reduces the amount of data required to obtain a confident mitochondrial haplogroup assignment.

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Neutrophil Extracellular Traps (NETs) are a key form of pro-inflammatory cell death of neutrophils characterized by the extrusion of extracellular webs of DNA containing bactericidal killing enzymes. NETosis is heavily implicated as a key driver of host damage in autoimmune diseases where injurious release of proinflammatory enzymes damage surrounding tissue and releases 70 known autoantigens. Recent evidence shows that both neutrophils and NETosis have a role to play in carcinogenesis, both indirectly through triggering DNA damage through inflammation, and directly contributing to a pro-tumorigenic tumor microenvironment. In this mini-review, we summarize the current knowledge of the various mechanisms of interaction and influence between neutrophils, with particular attention to NETosis, and cancer cells. We will also highlight the potential avenues thus far explored where we can intercept these processes, with the aim of identifying promising prospective targets in cancer treatment to be explored in further studies.

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Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.

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Flagellar motility is essential for the cell morphology, viability, and virulence of pathogenic kinetoplastids. Trypanosoma brucei flagella beat with a bending wave that propagates from the flagellum's tip to its base, rather than base-to-tip as in other eukaryotes. Thousands of dynein motor proteins coordinate their activity to drive ciliary bending wave propagation. Dynein-associated light and intermediate chains regulate the biophysical mechanisms of axonemal dynein. Tctex-type outer arm dynein light chain 2 (LC2) regulates flagellar bending wave propagation direction, amplitude, and frequency in Chlamydomonas reinhardtii. However, the role of Tctex-type light chains in regulating T. brucei motility is unknown. Here, we used a combination of bioinformatics, in-situ molecular tagging, and immunofluorescence microscopy to identify a Tctex-type light chain in the procyclic form of T. brucei (TbLC2). We knocked down TbLC2 expression using RNAi in both wild-type and FLAM3, a flagellar attachment zone protein, knockdown cells and quantified TbLC2's effects on trypanosome cell biology and biophysics. We found that TbLC2 knockdown reduced the directional persistence of trypanosome cell swimming, induced an asymmetric ciliary bending waveform, modulated the bias between the base-to-tip and tip-to-base beating modes, and increased the beating frequency. Together, our findings are consistent with a model of TbLC2 as a down-regulator of axonemal dynein activity that stabilizes the forward tip-to-base beating ciliary waveform characteristic of trypanosome cells. Our work sheds light on axonemal dynein regulation mechanisms that contribute to pathogenic kinetoplastids' unique tip-to-base ciliary beating nature and how those mechanisms underlie dynein-driven ciliary motility more generally.

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The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and potentially other psychedelics. We assessed neuroimaging observations with psilocybin among participants with MDD and healthy populations. A systematic search was conducted on PubMed, Google Scholar and PsycINFO from database inception to November 17th, 2021. The study quality (i.e., risk of bias) was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A total of ten studies evaluated psilocybin in healthy populations and three studies assessed psilocybin in MDD participants using neuroimaging techniques. Following psilocybin administration, a decrease in amygdala activity and a reduction in depressive symptoms was observed in two studies. Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, was seen in healthy populations. There was high heterogeneity in methodology (e.g., dosing schedule and imaging methods) amongst included studies. Longitudinal studies are needed to further elucidate psilocybin treatment for MDD, its long-term effects and the possibility of sustained therapeutic effects.

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Abstract Introduction Audit and education are essential pre-requisites in the review and update of blood transfusion practices. Although standard guidelines on appropriate utilization of blood components exists, erroneous use of blood components with no justification still continues. This study evaluates appropriateness of blood transfusion in obstetric settings and identifies key areas requiring educational intervention to improve blood transfusion practice toward the evidence-based at our hospital. Method This was a prospective observational study on the analysis of blood transfusion requisition forms for obstetric patients before and after educational intervention, performed in two Phases from September 2011 to August 2012 and October 2012 to September 2013. The appropriateness of blood utilization was assessed against the Royal College of Obstetricians and Gynecologists Guidelines for blood transfusion and Green-Top Guideline no. 47. Data required for the study were obtained from department records and statistical analysis was performed using the SPSS, version 20 (IBM, USA). Results The total transfusion episodes were 214 in 51 patients and 181 in 43 patients in Phases 1 and 2, respectively. Fresh frozen plasma was the most misused blood component, next to whole blood in Phase 1. However, appropriate utilization of components, including cryoprecipitate (6.6%), reduction in whole blood (34.5-14.4%) and single unit transfusion (23.3-18.2%) were observed in Phase 2. Inappropriate use of blood components, namely, packed red blood cells and fresh frozen plasma dropped significantly (p < 0.05) from 29.7% to 13.1% and 45.1% to 22.5%, respectively, with the exclusion of platelet concentrate (33.3-20.6%, p-value 0.414). Conclusion Audit and targeted education helped in optimizing transfusion practices in the obstetric setting.

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The dynein family of microtubule minus-end-directed motor proteins drives diverse functions in eukaryotic cells, including cell division, intracellular transport, and flagellar beating. Motor protein processivity, which characterizes how far a motor walks before detaching from its filament, depends on the interaction between its microtubule-binding domain (MTBD) and the microtubule. Dynein's MTBD switches between high- and low-binding affinity states as it steps. Significant structural and functional data show that specific salt bridges within the MTBD and between the MTBD and the microtubule govern these affinity state shifts. However, recent computational work suggests that nonspecific, long-range electrostatic interactions between the MTBD and the microtubule may also play an important role in the processivity of dynein. To investigate this hypothesis, we mutated negatively charged amino acids remote from the dynein MTBD-microtubule-binding interface to neutral residues and measured the binding affinity using microscale thermophoresis and optical tweezers. We found a significant increase in the binding affinity of the mutated MTBDs for microtubules. Furthermore, we found that charge screening by free ions in solution differentially affected the binding and unbinding rates of MTBDs to microtubules. Together, these results demonstrate a significant role for long-range electrostatic interactions in regulating dynein-microtubule affinity. Moreover, these results provide insight into the principles that potentially underlie the biophysical differences between molecular motors with various processivities and protein-protein interactions more generally.

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INTRODUCTION: Audit and education are essential pre-requisites in the review and update of blood transfusion practices. Although standard guidelines on appropriate utilization of blood components exists, erroneous use of blood components with no justification still continues. This study evaluates appropriateness of blood transfusion in obstetric settings and identifies key areas requiring educational intervention to improve blood transfusion practice toward the evidence-based at our hospital. METHOD: This was a prospective observational study on the analysis of blood transfusion requisition forms for obstetric patients before and after educational intervention, performed in two Phases from September 2011 to August 2012 and October 2012 to September 2013. The appropriateness of blood utilization was assessed against the Royal College of Obstetricians and Gynecologists Guidelines for blood transfusion and Green-Top Guideline no. 47. Data required for the study were obtained from department records and statistical analysis was performed using the SPSS, version 20 (IBM, USA). RESULTS: The total transfusion episodes were 214 in 51 patients and 181 in 43 patients in Phases 1 and 2, respectively. Fresh frozen plasma was the most misused blood component, next to whole blood in Phase 1. However, appropriate utilization of components, including cryoprecipitate (6.6%), reduction in whole blood (34.5-14.4%) and single unit transfusion (23.3-18.2%) were observed in Phase 2. Inappropriate use of blood components, namely, packed red blood cells and fresh frozen plasma dropped significantly (p<0.05) from 29.7% to 13.1% and 45.1% to 22.5%, respectively, with the exclusion of platelet concentrate (33.3-20.6%, p-value 0.414). CONCLUSION: Audit and targeted education helped in optimizing transfusion practices in the obstetric setting.

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Background Extant literature has identified Major Depressive Disorder (MDD) as a comorbid disorder in individuals with seropositive human immunodeficiency disorder (HIV), and this may affect HIV-treatment efficacy. However, there is a paucity of literature evaluating the effects of antidepressant use on antiretroviral therapies (ART) in HIV-positive individuals. Herein, the following review assesses the effects of antidepressant medications on ART adherence in HIV-positive individuals with diagnosed MDD. Methods A systematic search on PubMed, Scopus, Web of Science, and Google Scholar search engines were conducted between database inception to June 12th, 2020 using the search and MeSH terms: (HIV) AND (antiretroviral or treatment) AND (depress*) AND (antidepressants) AND (adherence). Results We identified nine articles that evaluated ART adherence in HIV-positive individuals using antidepressants. Of the nine included articles, eight articles evaluated participants undergoing ART, and one article evaluated participants undergoing highly active antiretroviral therapy (HAART). Our primary findings suggest that patients who took antidepressant treatment for depression demonstrated greater adherence to HIV treatments and a reduction in missed HIV medication dosage. Limitations The heterogeneity of study design between the included studies was high. Conclusion The current review suggests that response to antidepressant medication may improve adherence to HIV treatments in HIV-positive individuals with comorbid depression. Further studies should expand the findings to explore the effects of disparate psychotropic agents on adherence behaviors among patients with HIV to identify the benefits of these agents on long-term health outcomes in this vulnerable clinical population.

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Monoclonal antibodies (mAbs) are promising alternatives to treat infectious diseases, especially given their potential for applications in combination therapies with antimicrobial drugs to enhance the antifungal efficacy. Protection mediated by mAbs used to treat experimental paracoccidioidomycosis (PCM) has been demonstrated previously. Our aim in the present work was to characterize a monoclonal antibody (mAbF1.4) raised against a cell wall glycoconjugate fraction of Paracoccidioides spp. and to analyze its efficacy combined with trimethoprim-sulfamethoxazole (TMP/SMX) as treatment for experimental PCM. We demonstrated that the epitope recognized by mAbF1.4 is consistent with branched glucose residues present on a cell wall ß-glucan polymer. In vitro, mAbF1.4 increased the phagocytic capacity and nitric oxide concentration induced by the macrophage cell line J774.1A, and this resulted in a significant reduction in the viability of the opsonophagocytized yeasts. In vivo, we detected a significant reduction in pulmonary fungal burdens of mice treated with mAbF1.4 in association with TMP/SMX, which correlated with increased pulmonary concentrations (determined by ELISA) of IFN- Î³, TNF-α, IL-10 and IL-17. In parallel, we observed a decrease in IL-4, suggesting that the treatment was associated with a mixed Th1-Th17 type immune response. Histopathology of lung segments from mice receiving the combination therapy showed a significant reduction in granulomas, which were well-defined, and improved maintenance of lung architecture. These findings demonstrate that mAbF1.4 + TMP/SMX therapy is a promising approach to combat PCM as well as decrease disease sequelae and highlights the potential benefits of immune mediators in PCM combined immunotherapy.

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OBJECTIVE: Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation). METHODS: PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese). RESULTS: Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity. CONCLUSIONS: Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression. LIMITATIONS: There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.

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BACKGROUND: A significant proportion of anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis eventually progresses to end-stage renal disease (ESRD) thus requiring long-term dialysis. There is no consensus about which dialysis modality is more recommended for those patients with associated vasculitis (AAV-ESRD). The primary objective of this study was to compare patient survival in patients with AAV-ESRD treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: This double-center retrospective cohort study included dialysis-dependent patients who were treated with HD or PD. Clinical data were collected under standard format. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity at diagnosis and organ damage was assessed using the vasculitis damage index (VDI) at dialysis initiation. RESULTS: In total, 85 patients were included: 64 with hemodialysis and 21 with peritoneal dialysis. The patients with AAV-PD were much younger than the AAV-HD patients (48 vs. 62, P < 0.01) and more were female (76.2 vs. 51.6%, P = 0.05). The laboratory data were almost similar. The comorbidities, VDI score, and immuno-suppressive therapy at dialysis initiation were almost no statistical difference. Patient survival rates between HD and PD at 1 year were 65.3 vs. 90% (P = 0.062), 3 year were 59.6 vs. 90% (P < 0.001), and 5 years were 59.6 vs. 67.5% (P = 0.569). The overall survival was no significant difference between the two groups (P = 0.086) and the dialysis modality (HD or PD) was not shown to be an independent predictor for all-cause death (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.31-1.7; P = 0.473). Cardio-cerebrovascular events were the main cause of death among AAV-HD patients while infection in patients with AAV-PD. CONCLUSION: These results provide real-world data that the use of either hemodialysis or peritoneal dialysis modality does not affect patient survival for patients with AAV-ESRD who need long-term dialysis.

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Histoplasma capsulatum is a major endemic mycosis. Our laboratories have demonstrated that H. capsulatum produces extracellular vesicles (EV) that are loaded with diverse compounds that influence virulence. We have further shown that H. capsulatum dynamically regulates the loading and release of fungal EV in response to stimuli and growth conditions. This chapter details the current knowledge of EV biology in H. capsulatum and the impact of this information on our understanding of this important process that is closely linked to pathogenesis.

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