Factores asociados a la malnutrición en menores de 5 años, Hospital IESS Latacunga. Periodo septiembre 2018-junio 2019

El presente estudio es de tipo descriptivo, transversal analítico se desarrolló en el Hospital IEES Latacunga en niños menores de 5 años hospitalizados en esta casa de salud con diagnóstico de malnutrición en el periodo comprendido entre Septiembre 2018- Junio 2019. El universo estuvo constituido por 525 pacientes menores de 5 años hospitalizados en este periodo y la muestra la constituyen todos aquellos que presentaron el diagnóstico de malnutrición (desnutrición aguda moderada, desnutrición aguda severa, sobrepeso y obesidad). Se utilizaron criterios de inclusión como (pacientes con diagnóstico de desnutrición aguda moderada, desnutrición aguda severa, sobrepeso y obesidad, en menores de 5 años, que hayan sido hospitalizados en el tiempo de estudio, niños de ambos sexos) y de exclusión (pacientes con diagnóstico quirúrgico y patologías crónicas previas). El procesamiento de los datos se realizó mediante el calculó el intervalo de confianza del 95 % para las variables de mayor interés, la prueba de Chi cuadrado con grado de significancia de 0,05, todos los datos hallados fueron tabulados en IBM SPSS. El resultado que se obtuvo fue una asociación significativa entre los factores de riesgo que son la ablactación y el estado civil de la madre con la malnutrición por defecto en los niños menores de 5 años. Se recomienda realizar más estudios de seguimiento.The objective of this research was to perform a descriptive, cross-sectional analytical study at the IESS Latacunga Hospital in children under 5 years of age hospitalized in this health house with diagnosis of malnutrition in the period between September 2018 - June 2019. The universe consisted of all patients under 5 years hospitalized in this period and the sample is made up of all those who presented the diagnosis of malnutrition (moderate acute malnutrition, severe acute malnutrition, overweight and obesity). Inclusion criteria such as (patients with a diagnosis of moderate acute malnutrition, severe acute malnutrition, overweight and obesity in children under 5 years of age, who have been hospitalized at the time of study, children of both sexes) and exclusion (patients with diagnosis were used) surgical and previous chronic pathologies). he data processing was performed by calculating the 95% confidence interval for the variables of greatest interest, the Chi-square test with degree of significance of 0,05, all the data found were tabulated in IBM SPSS. The result obtained was a significant association between the risk factors that are ablactation and the marital status of the mother with default malnutrition in children under 5 years. Further follow-up studies are recommended

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS

Potential Use of Nitrogen-Doped Carbon Nanotube Sponges as Payload Carriers Against Malignant Glioma

Glioblastoma is the most aggressive brain tumor with a low median survival of 14 months. The only Food and Drug Administration (FDA)-approved treatment for topical delivery of the cancer drug carmustine is Gliadel. However, its use has been associated with several side-effects, mainly provoked by a mass effect. Nitrogen-doped carbon nanotube sponges (N-CNSs) are a new type of nanomaterial exhibiting high biocompatibility, and they are able to load large amounts of hydrophobic drugs, reducing the amount of carriers. This study evaluated the use of N-CNSs as potential carmustine carriers using malignant glioma cell lines. N-CNSs were characterized by nanoparticle tracking analysis and transmission electron microscopy. The biocompatibility of N-CNSs was determined in glioma cell lines and in primary astrocytes. Afterward, N-CNSs were loaded with carmustine (1:10 w/w), and the drug and liberation efficiency, as well as cytotoxicity induction, were determined. N-CNSs presented a homogeneous size distribution formed by round nanotubes, without induced cytotoxicity, at concentrations below 40 µg/mL. The N-CNSs loaded with carmustine exhibited a continuous kinetic release of carmustine with a maximum release after 72 h. The cytotoxic effect of N-CNSs loaded with carmustine was similar to that of carmustine alone. The results demonstrated that N-CNSs are a biocompatible nanostructure that could be used as carriers for the tumoral load of large amounts of chemotherapeutic agents

Explorando el vínculo entre la enfermedad cerebrovascular y la COVID-19

La enfermedad por coronavirus 2019 (COVID-19) ha generado una carga sanitaria internacional pr&aacute;cticamente insostenible, alcanzando el estatus de pandemia. Aunque la infecci&oacute;n puede ocurrir en todo tipo de individuos, se ha observado que la edad avanzada, al igual que la presencia de m&uacute;ltiples comorbilidades, se correlaciona positivamente con la tasa de infecci&oacute;n y mortalidad. Los pulmones parecen ser el &oacute;rgano diana de la infecci&oacute;n; sin embargo, no es infrecuente que el paciente presente afectaci&oacute;n en otros &oacute;rganos. Resulta de particular inter&eacute;s que la enfermedad cerebrovascular (ECV) ha sido reportada en algunos casos severos de COVID-19. Incluso, se ha advertido que el ictus podr&iacute;a cursar como forma de presentaci&oacute;n de la COVID-19. A pesar de que la edad y los antecedentes como la hipertensi&oacute;n arterial y la diabetes mellitus juegan un papel preponderante en el desarrollo de ECV, estos no parecen ser los &uacute;nicos mecanismos subyacentes en el paciente con COVID-19. Se ha reportado que pacientes con antecedentes de ECV tienen un peor pron&oacute;stico en relaci&oacute;n con la COVID-19, sugiriendo una relaci&oacute;n bidireccional entre estas entidades. Esta revisi&oacute;n tiene como objetivo revisar los mecanismos fisiopatol&oacute;gicos que expliquen la conexi&oacute;n entre la ECV y la COVID-19

Lactate-Loaded Nanoparticles Induce Glioma Cytotoxicity and Increase the Survival of Rats Bearing Malignant Glioma Brain Tumor

A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate homeostasis depends on the proper functioning of intracellular lactate regulation systems, such as transporters and enzymes involved in its synthesis and degradation, with evidence that an intracellular lactate overload generates metabolic stress on tumor cells and tumor cell death. We propose that the delivery of a lactate overload carried in nanoparticles, allowing the intracellular release of lactate, would compromise the survival of tumor cells. We synthesized and characterized silica and titania nanoparticles loaded with lactate to evaluate the cellular uptake, metabolic activity, pH modification, and cytotoxicity on C6 cells under normoxia and chemical hypoxia, and, finally, determined the survival of an orthotopic malignant glioma model after in situ administration. A dose-dependent reduction in metabolic activity of treated cells under normoxia was found, but not under hypoxia, independent of glucose concentration. Lactated-loaded silica nanoparticles were highly cytotoxic (58.1% of dead cells) and generated significant supernatant acidification. In vivo, lactate-loaded silica nanoparticles significantly increased the median survival time of malignant glioma-bearing rats (p = 0.005) when administered in situ. These findings indicate that lactate-loaded silica nanoparticles are cytotoxic on glioma cells in vitro and in vivo

Gene Cloning, Recombinant Expression, Characterization, and Molecular Modeling of the Glycolytic Enzyme Triosephosphate Isomerase from Fusarium oxysporum

Triosephosphate isomerase (TPI) is a glycolysis enzyme, which catalyzes the reversible isomerization between dihydroxyactetone-3-phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). In pathogenic organisms, TPI is essential to obtain the energy used to survive and infect. Fusarium oxisporum (Fox) is a fungus of biotechnological importance due to its pathogenicity in different organisms, that is why the relevance of also biochemically analyzing its TPI, being the first report of its kind in a Fusarium. Moreover, the kinetic characteristics or structural determinants related to its function remain unknown. Here, the Tpi gene from F. oxysporum was isolated, cloned, and overexpressed. The recombinant protein named FoxTPI was purified (97% purity) showing a molecular mass of 27 kDa, with optimal activity at pH 8.0 and and temperature of 37 &deg;C. The values obtained for Km and Vmax using the substrate GAP were 0.47 &plusmn; 0.1 mM, and 5331 &mu;mol min&minus;1 mg&minus;1, respectively. Furthemore, a protein structural modeling showed that FoxTPI has the classical topology of TPIs conserved in other organisms, including the catalytic residues conserved in the active site (Lys12, His94 and Glu164). Finally, when FoxTPI was analyzed with inhibitors, it was found that one of them inhibits its activity, which gives us the perspective of future studies and its potential use against this pathogen

Kinetic and Molecular Docking Studies to Determine the Effect of Inhibitors on the Activity and Structure of Fused G6PD::6PGL Protein from Trichomonas vaginalis

Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis (T. vaginalis), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite&rsquo;s energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC50, the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors

An Overall View of the Functional and Structural Characterization of Glucose-6-Phosphate Dehydrogenase Variants in the Mexican Population

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting an estimated 500 million people worldwide, is a genetic disorder that causes human enzymopathies. Biochemical and genetic studies have identified several variants that produce different ranges of phenotypes; thus, depending on its severity, this enzymopathy is classified from the mildest (Class IV) to the most severe (Class I). Therefore, understanding the correlation between the mutation sites of G6PD and the resulting phenotype greatly enhances the current knowledge of enzymopathies’ phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments for patients with G6PD deficiency. In this review, we analyzed and compared the structural and functional data from 21 characterized G6PD variants found in the Mexican population that we previously characterized. In order to contribute to the knowledge regarding the function and structure of the variants associated with G6PD deficiency, this review aimed to determine the molecular basis of G6PD and identify how these mutations could impact the structure, stability, and function of the enzyme and its relation with the clinical manifestations of this disease