A systematic review and narrative synthesis of health literacy interventions among Spanish speaking populations in the United States.

BACKGROUND: While many populations struggle with health literacy, those who speak Spanish preferentially or exclusively, including Hispanic, immigrant, or migrant populations, may face particular barriers, as they navigate a predominantly English-language healthcare system. This population also faces greater morbidity and mortality from treatable chronic diseases, such as hypertension and diabetes. The aim of this systematic review was to describe existing health literacy interventions for patients with a Spanish-language preference and present their effectiveness. METHODS: We carried out a systematic review where Web of Science, EMBASE, and PubMed were queried using MeSH terms to identify relevant literature. Included articles described patients with a Spanish-language preference participating in interventions to improve health literacy levels in the United States. Screening and data abstraction were conducted independently and in pairs. Risk of bias assessments were conducted using validated appraisal tools. RESULTS: A total of 2823 studies were identified, of which 62 met our eligibility criteria. The studies took place in a variety of community and clinical settings and used varied tools for measuring health literacy. Of the interventions, 28 consisted of in-person education and 27 implemented multimedia education, with 89% of studies in each category finding significant results. The remaining seven studies featured multimodal interventions, all of which achieved significant results. CONCLUSION: Successful strategies included the addition of liaison roles, such as promotores (Hispanic community health workers), and the use of multimedia fotonovelas (photo comics) with linguistic and cultural adaptations. In some cases, the external validity of the results was limited. Improving low health literacy in patients with a Spanish-language preference, a population with existing barriers to high quality of care, may help them better navigate health infrastructure and make informed decisions regarding their health. REGISTRATION: PROSPERO (available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257655.t ).

Correction: Unbridled Threat of Gas Gangrene in a Patient With Uncontrolled Diabetes Mellitus: A Compelling Case Report of Clostridium perfringens Infection.

[This corrects the article DOI: 10.7759/cureus.50614.].

Enhancing analysis of neo-formed contaminants in two relevant food global commodities: Coffee and cocoa.

Neo-formed contaminants (NFCs) are common in many foods, especially those subjected to high-temperature processing. Among these contaminants, products arising from the Maillard reaction, sugar reduction, thermal degradation of polyphenols and lipid oxidation, including acrylamide, furan, furfuryl alcohol, and hydroxymethylfurfural, are consistently linked to potential neoplastic effects. NFCs are found in globally traded commodities like coffee and cocoa, posing a significant risk due to their frequent consumption by consumers. A direct correlation exists between consumption frequency, exposure levels, and health risks. Hence, it's crucial to establish reliable methods to determine levels in both matrices, aiming to mitigate their formation and minimise risks to consumers. This review offers a comprehensive examination, discussion, and identification of emerging trends and opportunities to enhance existing methodologies for extracting and quantifying NFCs in coffee and cocoa. By presenting an in-depth analysis of performance parameters, we aim to guide the selection of optimal extraction techniques for quantifying individual NFCs. Based on the reviewed data, headspace extraction is recommended for furan, while solid and dispersive solid phase extractions are preferred for acrylamide when quantified using gas and liquid chromatography, respectively. However, it is worth noting that the reported linearity tests for certain methods did not confirm the absence of matrix effects unless developed through standard addition, leading to uncertainties in the reported values. There is a need for further research to verify method parameters, especially for determining NFCs like furfuryl alcohol. Additionally, optimising extraction and separation methods is essential to ensure complete compound depletion from samples. Ideally, developed methods should offer comprehensive NFC determination, reduce analysis time and solvent use, and adhere to validation parameters. This review discusses current methods for extracting and quantifying NFCs in coffee and cocoa, highlighting emerging trends and emphasising the need to improve existing techniques, especially for compounds like furfuryl alcohol.

Efectos del ciclismo en la composición corporal e indicadores de riesgo metabólico / Effects of cycling on Body Composition and Metabolic Risk Indicators

Introducción: El ciclismo es una actividad física que se practica de forma recreativa y como actividad laboral, en base a esto los beneficios en la salud varían. Sus efectos pueden extenderse en la regulación de la expresión de citocinas proinflamatorias en la obesidad; sin embargo, se deben estudiar detalles en los indicadores clínicos asociados a otras enfermedades crónico-degenerativas. Objetivo: Identificar los cambios en los parámetros clínicos que sirven como indicadores de riesgo metabólico en personas que realizan ciclismo como ejercicio habitual y como actividad laboral. Métodos: Se realizó una investigación de diseño transversal, descriptivo en el Estado de México, México. Se formaron 3 grupos de 16 participantes provenientes de Toluca y municipios aledaños. Se realizaron mediciones de composición corporal y análisis bioquímicos para identificar las diferencias entre los grupos a través de la prueba t- student y el análisis de varianza ANOVA. Resultados: Los análisis estadísticos reportaron diferencias significativas en las concentraciones de lipoproteínas de alta densindad y triglicéridos. Para el grupo de los conductores de bicitaxi fue más favorable, se detalla como el tiempo de la actividad ayuda a mantener los parámetros de composición corporal como el porcentaje del tejido muscular y adiposo. Conclusiones: Los beneficios del ciclismo se presentaron con diferentes grados de eficiencia de acuerdo con la modalidad en la que se practican. Las variables no cambian de forma significativa en ningún grupo, pueden ser dependientes de otras variables como la alimentación(AU)

Introduction: Cycling is a physical activity, which is practiced recreationally and as a work activity. Its effects may extend to the regulation of the expression of proinflammatory cytokines in obesity; however, details should be studied in the clinical indicators associated with other chronic-degenerative diseases. Objective: To identify changes in clinical parameters that serve as indicators of metabolic risk in people who perform cycling as a regular exercise and as a work activity. Methods: A cross-sectional and descriptive design research was carried out in the State of Mexico, Mexico. Three groups of 16 participants were formed from Toluca and surrounding municipalities. Body composition measurements and biochemical analyzes were performed to identify differences between groups through Student's t test and ANOVA analysis of variance. Results: Statistical analyzes reported significant differences in HDL and triglyceride concentrations. For the group of pedicab drivers it was more favorable, it is detailed how the time of the activity helps to maintain body composition parameters such as the percentage of muscle and adipose tissue. Conclusions: The benefits of cycling were presented with different degrees of efficiency according to the modality in which they are practiced. The variables do not change significantly in any group and may be dependent on other variables such as diet(AU)

Unbridled Threat of Gas Gangrene in a Patient With Uncontrolled Diabetes Mellitus: A Compelling Case Report of Clostridium perfringens Infection.

Clostridium perfringens, a Gram-positive anaerobic bacterium, is well-known for its association with gas gangrene, a severe and rapidly progressing infection characterized by tissue gas production and necrosis. In this case report, we present the instance of a 64-year-old male with poorly controlled diabetes mellitus who developed a C. perfringens-related infection following a traumatic foot wound. The report emphasizes the critical significance of early diagnosis and aggressive treatment in C. perfringens infections, particularly in patients with underlying risk factors. Detailed accounts of clinical findings, laboratory results, computed tomography, and surgical interventions are provided. A multidisciplinary approach proved essential for successful management. The inherent scholarly value of this case is substantiated by its meticulous documentation of the clinical trajectory, diagnostic modalities, and treatment modalities employed. The intricate collaboration across diverse medical disciplines, the uncommon manifestation of the infection following a traumatic foot wound, and the favorable outcome achieved through prompt and multidisciplinary intervention collectively contribute to the exceptional nature and didactic significance of this case. The dissemination of such clinical experiences assumes paramount importance in advancing medical scholarship, cultivating awareness, and engendering a profound comprehension of the complexities associated with C. perfringens infections, thereby enriching the wider scientific and medical community.

Exploring the effect of utilising organic acid solutions in ultrasound-assisted extraction of pectin from apple pomace, and its potential for biomedical purposes.

Biomass resulting from food production represents valuable material to recover different biomolecules. In our study, we used apple pomace to obtain pectin, which is traditionally extracted using mineral acids. Our hypothesis consisted of carrying out extractions with organic acids, assisted by ultrasound, by varying processing parameters including time, temperature, and type of acid. The analytical determinations of galacturonic acid content, methoxylation and esterification degree, ζ-potential and extraction yield were used as pectin quality indicators. Pectins extracted using treatment conditions with better performance were assessed biologically in vitro for their potential to be used in biomedical applications. Overall, the extracted pectin presented a galacturonic acid content, methoxylation and esterification degree ranged from 19.7 to 67%, 26.8-41.4% and 58-65.2% respectively, and were negatively charged (-24.1 to -13.2 mV). It was found that factors of time and temperature greatly influenced the response variables excepting the esterification degree, while the acid type influenced the ζ-potential, methoxylation and esterification degrees. Additionally, it was seen that the longer extraction time (50 min) and higher temperature (50 °C) exhibited the better extraction yield (∼10.9%). Finally, the selected pectin showed high cytocompatibility up to 500 µg/mL of concentration when seeded with Neonatal Normal Human Dermal Fibroblasts.

Epidemiological Profile and Social Welfare Index as Factors Associated with COVID-19 Hospitalization and Severity in Mexico City: A Retrospective Analysis.

Epidemiological data indicate that Mexico holds the 19th place in cumulative cases (5506.53 per 100,000 inhabitants) of COVID-19 and the 5th place in cumulative deaths (256.14 per 100,000 inhabitants) globally and holds the 4th and 3rd place in cumulative cases and deaths in the Americas region, respectively, with Mexico City being the most affected area. Several modifiable and non-modifiable risk factors have been linked to a poor clinical outcome in COVID-19 infection; however, whether socioeconomic and welfare factors are associated with clinical outcome has been scanty addressed. This study tried to investigate the association of Social Welfare Index (SWI) with hospitalization and severity due to COVID-19. A retrospective analysis was conducted at the Centro Médico Nacional "20 de Noviembre"-ISSSTE, based in Mexico City, Mexico. A total of 3963 patients with confirmed or suspected COVID-19, registered from March to July 2020, were included, retrieved information from the Virology Analysis and Reference Unit Database. Demographic, symptoms and clinical data were analyzed, as well as the SWI, a multidimensional parameter based on living and household conditions. An adjusted binary logistic regression model was performed in order to compare the outcomes of hospitalization, mechanical ventilation requirement (MVR) and mortality between SWI categories: Very high (VHi), high (Hi), medium (M) and low (L). The main findings show that lower SWI were independently associated with higher probability for hospital entry: VHi vs. Hi vs. M vs. L-SWI (0 vs. +0.24 [OR = 1.24, CI95% 1.01-1.53] vs. +0.90 [OR = 1.90, CI95% 1.56-2.32] vs. 0.73 [OR = 1.73, CI95% 1.36-2.19], respectively); Mechanical Ventilation Requirement: VHi vs. M vs. L-SWI (0 vs. +0.45 [OR = 1.45, CI95% 1.11-1.87] vs. +0.35 [OR = 1.35, CI95% 1.00-1.82]) and mortality: VHi vs. Hi vs. M (0 vs. +0.54 [OR = 1.54, CI95% 1.22-1.94] vs. +0.41 [OR = 1.41, CI95% 1.13-1.76]). We concluded that SWI was independently associated with the poor clinical outcomes in COVID-19, beyond demographic, epidemiological and clinical characteristics.

White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

Impact of heterogeneously crosslinked calcium alginate networks on the encapsulation of ß-carotene-loaded beads.

This study investigated the impact of heterogeneity of crosslinking on a range of physical and mechanical properties of calcium alginate networks formed via external gelation with 0.25-2% sodium alginate and 2.5 and 5% CaCl2. Crosslinking in films with 1-2% alginate was highly heterogeneous, as indicated by their lower calcium content (35-7 mg Ca·g alginate-1) and apparent solubility (5-6%). Overall, films with 1-2% alginate showed higher resistance (tensile strength = 51-147 MPa) but lower elasticity (Elastic Modulus = 2136-10,079 MPa) than other samples more homogeneous in nature (0.5% alginate, Elastic Modulus = 1918 MPa). Beads with 0.5% alginate prevented the degradation of ß-carotene 1.5 times more efficiently than 1% beads (5% CaCl2) at any of the storage temperatures studied. Therefore, it was postulated that calcium alginate networks crosslinked to a greater extent and in a more homogeneous manner showed better mechanical performance and barrier properties for encapsulation applications.

Three-Dimensional Motor Nerve Organoid Generation.

A fascicle of axons is one of the major structural motifs observed in the nervous system. Disruption of axon fascicles could cause developmental and neurodegenerative diseases. Although numerous studies of axons have been conducted, our understanding of formation and dysfunction of axon fascicles is still limited due to the lack of robust three-dimensional in vitro models. Here, we describe a step-by-step protocol for the rapid generation of a motor nerve organoid (MNO) from human induced pluripotent stem (iPS) cells in a microfluidic-based tissue culture chip. First, fabrication of chips used for the method is described. From human iPS cells, a motor neuron spheroid (MNS) is formed. Next, the differentiated MNS is transferred into the chip. Thereafter, axons spontaneously grow out of the spheroid and assemble into a fascicle within a microchannel equipped in the chip, which generates an MNO tissue carrying a bundle of axons extended from the spheroid. For the downstream analysis, MNOs can be taken out of the chip to be fixed for morphological analyses or dissected for biochemical analyses, as well as calcium imaging and multi-electrode array recordings. MNOs generated with this protocol can facilitate drug testing and screening and can contribute to understanding of mechanisms underlying development and diseases of axon fascicles.

Simulations of breakthrough curves for fixed-bed column adsorption of cobalt (II) ions on spent tealeaves.

The objective of this study is to model the breakthrough adsorption curves of Co (II) ions using spent tealeaves in fixed-bed column experiments. Spent leaves of green tea (GT), peppermint tea (PM) and chamomile (CM) were packed in glass columns with a diameter of 2 cm and height of 15 cm, and used as filters for the removal of the pollutant. Aqueous solutions of cobalt (II) ions (100 mg/L) at pH 6 were prepared and pumped against gravity through the columns at a uniform flow rate of 5 mL/min. Breakthrough curves were fitted for the residual concentration data using the Thomas, Yoon-Nelson, and Clark models, with added empirical terms to delineate the lower tail of the breakthrough curve. These mathematical models were successfully linearized using the natural logarithm for parameter estimation. The results reveal that the Co (II) adsorption fits all three models for all the adsorbents. The Thomas model indicated that the calculated adsorption capacities followed the trend: PM > GT > CM with values of 59.7, 25.2, and 24.9 mg/g respectively. Moreover, CM showed the highest adsorption rates with all the mathematical models, whereas Yoon-Nelson theory provided evidence that PM has the longest 50% adsorption breakthrough among the adsorbents. Lastly, morphological and textural studies indicate that all spent leaves are good candidates as adsorbents due to their high surface heterogeneity. This study proposes the use of spent tealeaves as Co (II) adsorbents because they are inexpensive and environmentally beneficial.

VIH, dislipidemias y perspectivas de su evolución / HIV, dyslipidemias and perspectives of its evolution

Resumen Con el advenimiento de la terapia antirretroviral (ART), la infección por el virus de inmunodeficiencia humana (VIH) se ha convertido en una enfermedad crónica con complicaciones metabólicas importantes más acentuadas que en la población general. Mientras no se tenga una vacuna que erradique las tasas de infección y no exista una cura para esta pandemia, se debe ser más incisivo en el controlar las comorbilidades, entre las que destacan las alteraciones en el perfil de lípidos pues aumentan el riesgo cardiovascular.

Abstract With the advent of antiretroviral therapy (ART), infection with the human immunodeficiency virus (HIV) has become a chronic disease with major metabolic complications more pronounced than in the general population. While there is no vaccine to eradicate infection rates and there is no cure for this pandemic, it should be more incisive in controlling comorbidities, among which alterations in the lipid profile stand out as they increase cardiovascular risk.

Dietary patterns, central obesity and serum lipids concentration in Mexican adults.

INTRODUCTION: Introduction: dietary patterns (DP) analyse the relationship between consumption of foods or nutrients and disease or health outcomes. High prevalence of obesity in adults in Mexico is associated with factors such as high consumption of certain food groups and nutrients. However, few studies have been conducted to explore associations between dietary patterns and obesity in apparently healthy adults. Objective: to identify major dietary patterns (DP) associated with central-obesity (CO) and lipid concentrations in healthy adults. Methods: longitudinal study including usual dietary intakes derived from multiple 24-hour-recalls. Waist-circumference (WC) and biochemical measurements were obtained by standardized procedures and DP by principal component analysis. Adjusted-logistic regression was used to examine associations between DP, CO and serum-lipid concentrations. Results: three DP were identified: healthy-DP, risky-DP and empty-DP. Participants in the healthy-DP were more likely to have lower risk for central-obesity according to WC criteria (OR = 0.31, CI = 0.12, 0.82), p = 0.017, but also had the highest risk for elevated LDL-cholesterol (OR = 2.98, CI = 1.16, 7.66), p = 0.030. There was no significant association between risky and empty DP with obesity or overweight by body mass index (BMI), central-obesity by WC or serum lipid abnormalities. Conclusions: the healthy-DP is associated with lower risk for CO, with higher risk for elevated LDL-cholesterol. It is necessary to develop longitudinal studies of foods and nutritional analysis of the diet to clarify these associations, to promote the reduction of modifiable risk factors.

INTRODUCCIÓN: Introducción: los patrones de dieta (PD) analizan la relación entre el consumo de alimentos o nutrimentos con la salud y el desarrollo de enfermedades en poblaciones. La elevada prevalencia de obesidad en adultos mexicanos se asocia con factores como el elevado consumo de ciertos grupos de alimentos y nutrimentos. Sin embargo, pocos estudios han explorado la asociación entre los patrones dietéticos y la obesidad en adultos aparentemente sanos. Objetivo: identificar los patrones dietéticos (PD) asociados con la obesidad central (OC) y las concentraciones séricas de lípidos en adultos. Métodos: estudio longitudinal del consumo dietético obtenido de múltiples recordatorios de consumo de 24 horas. La circunferencia de cintura (CC) y las mediciones bioquímicas se obtuvieron mediante procedimientos estandarizados; los PD, por análisis del componente principal. Mediante regresión logística se identificaron las asociaciones entre PD, OC y las concentraciones séricas de lípidos. Resultados: se identificaron tres PD: PD saludable, PD de riesgo y PD vacío. Los participantes del PD saludable presentaron menor riesgo de OC de acuerdo con los criterios de la CC (OR = 0.31, CI = 0.12, 0.82), p = 0.017, pero también fueron los que presentaron mayor riesgo de cifras elevadas de colesterol-LDL (OR = 2.98. CI = 1.16, 7.66), p = 0.030. No hubo asociación estadísticamente significativa entre el PD de riesgo y el PD vacío con obesidad o sobrepeso por IMC, OC por CC o con la presencia de dislipidemias. Conclusiones: el PD saludable se asocia con un menor riesgo para OC pero con mayor riesgo de elevación del colesterol-LDL. Se necesitan estudios longitudinales para esclarecer estas asociaciones para promover la reducción de factores de riesgo modificables.

Dietary patterns, central obesity and serum lipids concentration in Mexican adults / Patrones de dieta, obesidad central y concentración de lípidos séricos en adultos mexicanos

Introduction: dietary patterns (DP) analyse the relationship between consumption of foods or nutrients and disease or health outcomes. High prevalence of obesity in adults in Mexico is associated with factors such as high consumption of certain food groups and nutrients. However, few studies have been conducted to explore associations between dietary patterns and obesity in apparently healthy adults. Objective: to identify major dietary patterns (DP) associated with central-obesity (CO) and lipid concentrations in healthy adults. Methods: longitudinal study including usual dietary intakes derived from multiple 24-hour-recalls. Waist-circumference (WC) and biochemical measurements were obtained by standardized procedures and DP by principal component analysis. Adjusted-logistic regression was used to examine associations between DP, CO and serum-lipid concentrations. Results: three DP were identifi ed: healthy-DP, risky-DP and empty-DP. Participants in the healthy-DP were more likely to have lower risk for central-obesity according to WC criteria (OR = 0.31, CI = 0.12, 0.82), p = 0.017, but also had the highest risk for elevated LDL-cholesterol (OR = 2.98, CI = 1.16, 7.66), p = 0.030. There was no significant association between risky and empty DP with obesity or overweight by body mass index (BMI), central-obesity by WC or serum lipid abnormalities. Conclusions: the healthy-DP is associated with lower risk for CO, with higher risk for elevated LDL-cholesterol. It is necessary to develop longitudinal studies of foods and nutritional analysis of the diet to clarify these associations, to promote the reduction of modifi able risk factors

Introducción: los patrones de dieta (PD) analizan la relación entre el consumo de alimentos o nutrimentos con la salud y el desarrollo de enfermedades en poblaciones. La elevada prevalencia de obesidad en adultos mexicanos se asocia con factores como el elevado consumo de ciertos grupos de alimentos y nutrimentos. Sin embargo, pocos estudios han explorado la asociación entre los patrones dietéticos y la obesidad en adultos aparentemente sanos. Objetivo: identificar los patrones dietéticos (PD) asociados con la obesidad central (OC) y las concentraciones séricas de lípidos en adultos. Métodos: estudio longitudinal del consumo dietético obtenido de múltiples recordatorios de consumo de 24 horas. La circunferencia de cintura (CC) y las mediciones bioquímicas se obtuvieron mediante procedimientos estandarizados; los PD, por análisis del componente principal. Mediante regresión logística se identificaron las asociaciones entre PD, OC y las concentraciones séricas de lípidos. Resultados: se identificaron tres PD: PD saludable, PD de riesgo y PD vacío. Los participantes del PD saludable presentaron menor riesgo de OC de acuerdo con los criterios de la CC (OR = 0.31, CI = 0.12, 0.82), p = 0.017, pero también fueron los que presentaron mayor riesgo de cifras elevadas de colesterol-LDL (OR = 2.98. CI = 1.16, 7.66), p = 0.030. No hubo asociación estadísticamente signifi cativa entre el PD de riesgo y el PD vacío con obesidad o sobrepeso por IMC, OC por CC o con la presencia de dislipidemias. Conclusiones: el PD saludable se asocia con un menor riesgo para OC pero con mayor riesgo de elevación del colesterol-LDL. Se necesitan estudios longitudinales para esclarecer estas asociaciones para promover la reducción de factores de riesgo modificables

Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic pathways, but these monogenic causes do not explain all cases of SRNS. METHODS: To identify novel monogenic causes of SRNS, we screened 665 patients by whole-exome sequencing. We then evaluated the in vitro functional significance of two genes and the mutations therein that we discovered through this sequencing and conducted complementary studies in podocyte-like Drosophila nephrocytes. RESULTS: We identified conserved, homozygous missense mutations of GAPVD1 in two families with early-onset NS and a homozygous missense mutation of ANKFY1 in two siblings with SRNS. GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5. Coimmunoprecipitation assays indicated interaction between GAPVD1 and ANKFY1 proteins, which also colocalized when expressed in HEK293T cells. Silencing either protein diminished the podocyte migration rate. Compared with wild-type GAPVD1 and ANKFY1, the mutated proteins produced upon ectopic expression of GAPVD1 or ANKFY1 bearing the patient-derived mutations exhibited altered binding affinity for active RAB5 and reduced ability to rescue the knockout-induced defect in podocyte migration. Coimmunoprecipitation assays further demonstrated a physical interaction between nephrin and GAPVD1, and immunofluorescence revealed partial colocalization of these proteins in rat glomeruli. The patient-derived GAPVD1 mutations reduced nephrin-GAPVD1 binding affinity. In Drosophila, silencing Gapvd1 impaired endocytosis and caused mistrafficking of the nephrin ortholog. CONCLUSIONS: Mutations in GAPVD1 and probably in ANKFY1 are novel monogenic causes of NS. The discovery of these genes implicates RAB5 regulation in the pathogenesis of human NS.

Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson's disease: possible involvement of different binding sites at the PPARγ receptor.

BACKGROUND: Neuroprotection with cannabinoids in Parkinson's disease (PD) has been afforded predominantly with antioxidant or anti-inflammatory cannabinoids. In the present study, we investigated the anti-inflammatory and neuroprotective properties of VCE-003.2, a quinone derivative of the non-psychotrophic phytocannabinoid cannabigerol (CBG), which may derive its activity at the peroxisome proliferator-activated receptor-γ (PPARγ). The compound is also an antioxidant. METHODS: We evaluated VCE-003.2 in an in vivo [mice subjected to unilateral intrastriatal injections of lipopolysaccharide (LPS)] model of PD, as well as in in vitro (LPS-exposed BV2 cells and M-213 cells treated with conditioned media generated from LPS-exposed BV2 cells) cellular models. The type of interaction of VCE-003.2 at the PPARγ receptor was furtherly investigated in bone marrow-derived human mesenchymal stem cells (MSCs) and sustained with transcriptional assays and in silico docking studies. RESULTS: VCE-003.2 has no activity at the cannabinoid receptors, a fact that we confirmed in this study using competition studies. The administration of VCE-003.2 to LPS-lesioned mice attenuated the loss of tyrosine hydroxylase (TH)-containing nigrostriatal neurons and, in particular, the intense microgliosis provoked by LPS in the substantia nigra, measured by Iba-1/Cd68 immunostaining. The analysis by qPCR of proinflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) in the striatum showed they were markedly elevated by the LPS lesion and strongly reduced by the treatment with VCE-003.2. The effects of VCE-003.2 in LPS-lesioned mice implied the activation of PPARγ receptors, as they were attenuated when VCE-003.2 was co-administered with the PPARγ inhibitor T0070907. We then moved to some in vitro approaches, first to confirm the anti-inflammatory profile of VCE-003.2 in cultured BV2 cells exposed to LPS. VCE-003.2 was able to attenuate the synthesis and release of TNF-α and IL-1ß, as well as the induction of iNOS and cyclooxygenase-2 (COX-2) elicited by LPS in these cells. However, we found such effects were not reversed by GW9662, another classic PPARγ antagonist. Next, we investigated the neuroprotective effects of VCE-003.2 in cultured M-213 neuronal cells exposed to conditioned media generated from LPS-exposed cultured BV2 cells. VCE-003.2 reduced M-213 cell death, but again, such effects were not reversed by T0070907. Using docking analysis, we detected that VCE-003.2 binds both the canonical and the alternative binding sites in the PPARγ ligand-binding pocket (LBP). Functional assays further showed that T0070907 almost abolished PPARγ transcriptional activity induced by rosiglitazone (RGZ), but it did not affect the activity of VCE-003.2 in a Gal4-Luc system. However, T0070907 inhibited the effects of RGZ and VCE-003.2 on the expression of PPARγ-dependent genes upregulated in MSCs. CONCLUSIONS: We have demonstrated that VCE-003.2 is neuroprotective against inflammation-driven neuronal damage in an in vivo model of PD and in in vitro cellular models of neuroinflammation. Such effects might involve PPARγ receptors, although in silico and in vitro experiments strongly suggest that VCE-003.2 targets PPARγ by acting through two binding sites at the LBP, one that is sensitive to T0070907 (canonical binding site) and other that is not affected by this PPARγ antagonist (alternative binding site).

AKI in Children Hospitalized with Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. RESULTS: AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001). CONCLUSIONS: AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.

Current Trends, Evaluation, and Management of Pediatric Nephrolithiasis.

The incidence of pediatric nephrolithiasis has been steadily increasing for the past several decades, with a concomitant concerning increase in health care costs and burden to children with this disease. Recent population-based studies have also demonstrated a change in the current trends of pediatric nephrolithiasis that is characterized by a significant increase in the number of girls now being affected. While changes in diet and lifestyle, obesity prevalence, and even imaging practices have been proposed to contribute to the recent increase in pediatric nephrolithiasis, a definite underlying cause remains elusive. This situation is complicated by the fact that, unlike in adults, the trends occurring in pediatric nephrolithiasis have not been studied rigorously, which contributes to the paucity of data in children. The level of concern with the increasing incidence is raised by factors unique to pediatric nephrolithiasis that could expose an affected child to more complications. Factors such as variable clinical presentation, high recurrence of kidney stones associated with abnormalities of metabolism and the urinary tract, and the possible presence of rare genetic kidney stone diseases would require physicians to comprehensively evaluate patients presenting with kidney stones. The goal of evaluation is to identify modifiable risk factors and abnormalities for which targeted therapy can be prescribed. The goals of medical and surgical treatments are to eliminate the burden of kidney stones and prevent recurrence while simultaneously minimizing complications from interventions. Patients at high risk may benefit from a specialized kidney stone clinic staffed by a pediatric nephrologist, urologist, dietitian, and clinical nurse. Such a multidisciplinary clinic can help provide the medical and surgical support needed for patients at high risk and offer key opportunities to learn more about pediatric nephrolithiasis, thereby fueling the much-needed research in this field.