ppiGReMLIN: a graph mining based detection of conserved structural arrangements in protein-protein interfaces.

BACKGROUND: Protein-protein interactions (PPIs) are fundamental in many biological processes and understanding these interactions is key for a myriad of applications including drug development, peptide design and identification of drug targets. The biological data deluge demands efficient and scalable methods to characterize and understand protein-protein interfaces. In this paper, we present ppiGReMLIN, a graph based strategy to infer interaction patterns in a set of protein-protein complexes. Our method combines an unsupervised learning strategy with frequent subgraph mining in order to detect conserved structural arrangements (patterns) based on the physicochemical properties of atoms on protein interfaces. To assess the ability of ppiGReMLIN to point out relevant conserved substructures on protein-protein interfaces, we compared our results to experimentally determined patterns that are key for protein-protein interactions in 2 datasets of complexes, Serine-protease and BCL-2. RESULTS: ppiGReMLIN was able to detect, in an automatic fashion, conserved structural arrangements that represent highly conserved interactions at the specificity binding pocket of trypsin and trypsin-like proteins from Serine-protease dataset. Also, for the BCL-2 dataset, our method pointed out conserved arrangements that include critical residue interactions within the conserved motif LXXXXD, pivotal to the binding specificity of BH3 domains of pro-apoptotic BCL-2 proteins towards apoptotic suppressors. Quantitatively, ppiGReMLIN was able to find all of the most relevant residues described in literature for our datasets, showing precision of at least 69% up to 100% and recall of 100%. CONCLUSIONS: ppiGReMLIN was able to find highly conserved structures on the interfaces of protein-protein complexes, with minimum support value of 60%, in datasets of similar proteins. We showed that the patterns automatically detected on protein interfaces by our method are in agreement with interaction patterns described in the literature.

visGReMLIN: graph mining-based detection and visualization of conserved motifs at 3D protein-ligand interface at the atomic level.

BACKGROUND: Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces. RESULTS: To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets. CONCLUSIONS: We aimed to build a visual analytics-oriented web server to detect and visualize common motifs at the protein-ligand interface. visGReMLIN motifs can support users in gaining insights on the key atoms/residues responsible for protein-ligand interactions in a dataset of complexes.

Inhibition kinetics of digestive proteases for Anticarsia gemmatalis.

Anticarsia gemmatalis Hübner, 1818 (Lepidoptera) is a major pest of soybean in the Brazil. It is known that the reduction of proteolytic activity by the ingestion of protease inhibitors reduces digestion and larval development of the insects. Control via inhibition of the digestive enzymes necessitates deeper knowledge of the enzyme kinetics and the characterization of the inhibition kinetics of these proteases, for better understanding of the active centers and action mechanisms of this enzyme. Trypsin-like proteases found in the gut of Anticarsia gemmatalis were purified in a p-aminobenzamidine agarose column. Kinetic characterization showed KM 0.503 mM for the L-BApNA substrate; Vmax= 46.650 nM s-1; Vmax/[E]= 9.256 nM s-1 mg L-1 and Vmax/[E]/KM= 18.402 nM s-1 mg L-1 mM. The Ki values for the inhibitors benzamidine, berenil, SKTI and SBBI were 11.2 µM, 32.4 µM, 0.25 nM and 1.4 nM, respectively, and all revealed linear competitive inhibition. The SKTI showed the greatest inhibition, which makes it a promising subject for future research to manufacture peptide mimetic inhibitors.

Errores más comunes al redactar artículos médicos originales.

One of the skills that is more in need to be strengthened in the medical area is the dissemination of knowledge. For this reason, it is necessary to provide elements that promote training in scientific writing. Identifying the most common problems when writing medical original articles for publication will provide useful resources that should contribute to the generation of knowledge. There are multiple reasons that intervene for an original article not to be accepted in a medical journal, among which failure to follow instructions for authors and methodological, design and structural problems stand out. However, the aspect that most influences and that is seldom pointed out, is inadequate writing of research manuscripts, which becomes evident in the different sections that make up manuscripts. All the above-mentioned factors are the responsibility of the authors, and therefore must be taken care of properly. The purpose of this article is to identify the most common mistakes when writing original medical manuscripts, which, if avoided, will increase the possibility for research papers to be accepted for publication.

Una de las habilidades que más requiere ser fortalecida en el área médica es la difusión de conocimiento, por tal motivo, es necesario brindar elementos que promuevan la capacitación en redacción científica. Identificar cuáles son los problemas más comunes al redactar artículos médicos originales para su publicación proporcionará recursos útiles que contribuyan a la generación de conocimiento. Existen diversos motivos que intervienen para que un artículo original no sea aceptado en una revista médica, entre los que destacan falta de apego a las instrucciones para autores, problemas metodológicos y de diseño, así como de estructura, sin embargo, el aspecto que más influye y pocas veces se señala, es la redacción inadecuada de los escritos de investigación, la cual se hace patente en las diferentes secciones que componen los manuscritos. Todos los factores mencionados son responsabilidad de los autores, por lo que deben ser atendidos apropiadamente. El presente escrito tiene como objetivo señalar los errores más comunes al redactar escritos médicos originales, los cuales, de ser evitados, incrementarán la posibilidad de que sus trabajos de investigación sean aceptados para su publicación.

Association analysis of calpain 10 gene variants/haplotypes with gestational diabetes mellitus among Mexican women.

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays.  The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Medical Imagery: Cytomegalovirus sialadenitis in a patient with B-cell acute lymphoblastic leukemia.

Cytomegalovirus (CMV) can cause a broad range of diseases, with severity depending on immune status, comorbidities, and age. Initial CMV infection usually occurs in childhood and is typically asymptomatic, leading to lifelong latency. In immunocompromised patients, CMV can affect multiple organs, but salivary gland infections are rare. This study presents a case of a 66-year-old woman with B-cell acute lymphoblastic leukemia who developed swelling and pain in the right preauricular region during pre-transplant consolidation therapy. Despite a recent bone marrow biopsy indicating morphological remission and a flow cytometry analysis detecting only 0.04 % B lymphoblasts, she exhibited these symptoms. A CT scan revealed enlargement, hyperdensity, and enhancement of the right parotid glands, with accompanying subcutaneous edema. A biopsy of the right parotid gland showed a dense interstitial lymphoplasmacytic infiltrate with numerous Cowdry bodies and smaller granular cytoplasmic inclusions, all testing positive for CMV immunohistochemistry. The findings confirm the diagnosis of CMV sialadenitis in an immunocompromised patient. This case underscores the importance of considering CMV infections in similar clinical scenarios, particularly in patients with compromised immune systems.

Zinc and selenium supplementation on treated HIV-infected individuals induces changes in body composition and on the expression of genes responsible of naïve CD8+ T cells function.

Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.

A critical review of diabetes, glycemic control, and dental implant therapy.

OBJECTIVES: To systematically examine the evidence guiding the use of implant therapy relative to glycemic control for patients with diabetes and to consider the potential for both implant therapy to support diabetes management and hyperglycemia to compromise implant integration. MATERIAL AND METHODS: A systematic approach was used to identify and review clinical investigations directly assessing implant survival or failure for patients with diabetes. A MEDLINE (PubMED) database search identified potential articles for inclusion using the search strategy: (dental implants OR oral implants) AND (diabetes OR diabetic). Inclusion in this review required longitudinal assessments including at least 10 patients, with included articles assessed relative to documentation of glycemic status for patients. RESULTS: Although the initial search identified 129 publications, this was reduced to 16, for inclusion. Reported implant failure rates for diabetic patients ranged from 0% to 14.3%. The identification and reporting of glycemic control was insufficient or lacking in 13 of the 16 studies with 11 of these enrolling only patients deemed as having acceptable glycemic control, limiting interpretation of findings relative to glycemic control. Three of the 16 studies having interpretable information on glycemic control failed to demonstrate a significant relationship between glycemic control and implant failure, with failure rates ranging from 0% to 2.9%. CONCLUSIONS: Clinical evidence is lacking for the association of glycemic control with implant failure while support is emerging for implant therapy in diabetes patients with appropriate accommodations for delays in implant integration based on glycemic control. The role for implants to improve oral function in diabetes management and the effects of hyperglycemia on implant integration remain to be determined.

Conventional SLA and chemically modified SLA implants in patients with poorly controlled type 2 diabetes mellitus--a randomized controlled trial.

OBJECTIVE: The objective of this study was to evaluate the potential for a chemically modified Sand blasted, Large grit, Acid etched (SLA) surface, compared with a conventional SLA surface, to enhance implant healing and integration in poorly controlled diabetic patients, a group previously demonstrated to have compromises and delays in implant stabilization during the metabolically active healing period following implant placement. MATERIALS AND METHODS: The study enrolled 24 patients with type 2 diabetes, baseline HbA1c levels between 7.5-11.4%, and a minimum of two posterior mandibular tooth sites at least 4 months following extraction and appropriate for implant placement. Each patient, at a randomly selected site, received an implant with the conventional SLA surface; at the second site, the patient received an implant with the chemically modified SLA (modSLA) surface. Thus, 48 study implants were placed. Implant stability was assessed using Resonance Frequency Analysis (RFA). Readings were taken from the buccal and proximal directions for each implant. Implant stability (ISQ) was assessed at the time of surgical placement (baseline) and 2, 3, 4, 6, 8, 10, 12, and 16 weeks following implant placement. RESULTS: No significant differences in implant stability were observed between conventional SLA implants and modSLA implants, and the time courses of implant stabilization following implant placement were similar for the two implant types. Baseline ISQ and minimum ISQ was slightly higher in subjects with higher HbA1c levels, but were similar during 12-16 weeks following implant placement. Forty-seven (98%) of the 48 implants were determined to be successfully osseointegrated and continued to restoration. CONCLUSION: Implant stabilization was similar for the conventional SLA and chemically modified SLA implants in type 2 diabetic patients with relatively poor glycemic control. Furthermore, this study demonstrated clinically successful implant placement even in poorly controlled diabetic patients.

Using an existing denture to design a radiographic template for a two-implant mandibular overdenture.

This article describes a technique for modifying an existing mandibular complete denture for use as a radiographic template with a radiopaque light-activated calcium hydroxide (Ca(OH)(2)) preparation. This allows prosthetically driven treatment planning and the surgical placement of 2 implants to support the existing mandibular denture.

Normal weight obesity is associated with hypercholesterolemia and low muscle mass in persons living with HIV on antiretroviral treatment.

OBJECTIVES: Normal weight obesity (NWO) is defined as a condition of normal body weight, but with high body fat percentage. Clinical and immunologic implications of NWO in persons living with HIV (PLHIV) remain unknown. The aim of this study was to examine NWO prevalence and its associations with metabolic and immunologic measurements in a cohort of PLHIV on antiretroviral treatment (ART). METHODS: We enrolled 73 adult PLHIV on ART. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as body mass index 18.5 to 24.9 kg/m2 and body fat ≥25%. We determined triacylglycerols, total cholesterol, high-density lipoprotein, low-density lipoprotein, blood glucose, blood pressure, bone mineral density, inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor-α and IL-6) and CD4+ and CD8+ T-cell activation. RESULTS: The prevalence of NWO was 49% (36 of 73). Participants with NWO showed lower CD4+ T-cell percentage (25 versus 27%, P = 0.03), lower CD4/CD8 ratio (0.62 versus 0.82, P = 0.02), lower muscle mass (6.84 versus 7.11 kg/m2, P = 0.01) and higher prevalence of hypercholesterolemia (26% versus 6%, P = 0.03) than individuals with normal body composition. No differences in inflammation/activation markers were observed between groups (P > 0.05 in all cases). CONCLUSION: NWO was frequent in a cohort of Mexican PLHIV on ART and was associated with lower muscle mass, hypercholesterolemia, lower CD4+ T-cell percentage, and lower CD4/CD8 ratio. The incorporation of body fat measurements in the regular physical examination of PLHIV could contribute to early identification of the NWO condition and lead to better management of possible long-term morbidity.

Phase angle as predictor of malnutrition in people living with HIV/AIDS.

BACKGROUND: Phase angle (PhA), measured by bioelectrical impedance analysis (BIA) has been studied as an indicator of survival in people living with HIV (PLWH). However, it remains unclear whether PhA is associated with malnutrition or low CD4+ T-cell counts. OBJECTIVE: In this study, we assessed the discriminative capacity of PhA for malnutrition detection using Global Leadership Initiative on Malnutrition (GLIM) criteria in PLWH, aiming to propose cutoff points for this population. METHODS: This retrospective observational study included 427 adult PLWH (13% female). Participants were classified according to malnutrition status by using GLIM criteria. Body composition was assessed by using BIA. CD4+ T-cell counts were determined by flow cytometry. RESULTS: According to GLIM criteria, 30% of the participants were malnourished. Multivariate regression analysis showed that PhA (adjusted odds ratio [OR], 0.10; 95% CI, 0.05-0.18; P < 0.001), fat-mass percentage (adjusted OR, 0.86; 95% CI, 0.82-0.90; P < 0.001), and male sex (adjusted OR, 0.26; 95% CI, 0.09-0.76; P = 0.013) were independently associated with malnutrition. A PhA cutoff of 5.45° in men and 4.95° in women may predict malnutrition with sensitivity and specificity >70%. CONCLUSION: PhA could be a valid, useful, and simple predictor of malnutrition in PLWH.

Low phase angle is associated with 60-day mortality in critically ill patients with COVID-19.

BACKGROUND: Malnutrition status, body composition indicators, and bioelectrical impedance analysis (BIA) parameters have been associated with increased risk of death in several pathologies. The aim of this study was to describe the associations between phase angle (PhA) indicators obtained by BIA with length of hospital stay, days on mechanical ventilation, and 60-day mortality in critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a prospective cohort of mechanically ventilated patients with coronavirus disease 2019 (COVID-19). We assessed nutrition risk and body composition with BIA within 48 h from intensive care unit admission. Logistic and linear regression models were used to analyze the association between variables and clinical outcomes. Survival analysis by PhA value was performed using Kaplan-Meier curves. RESULTS: Sixty-seven patients were included. PhA (odds ratio [OR], 0.36; P = .002), standardized PhA (SPA) (OR, 0.45; P = .001), and extracellular water/total body water ratio (OR, 3.25; P = .002) were significant predictors of 60-day mortality. PhA <3.85° in females and <5.25° in males showed good and fair discrimination, respectively, for mortality prediction. Using cutoff values, low PhA was associated with a significantly increased risk of 60-day mortality (hazard ratio, 3.08; 95% CI, 1.12-8.41; P = .02). No association was detected for SPA. CONCLUSION: Low PhA values could be a predictor of 60-day mortality in critically ill patients with COVID-19. This biological marker could be incorporated as part of nutrition and mortality risk assessment in this population.

High nutritional risk using NUTRIC-Score is associated with worse outcomes in COVID-19 critically ill patients.

INTRODUCTION: Background: nutritional risk has been associated with worse outcomes at the critical care unit. The aim of this study was to describe the association between nutritional risk and length of stay, days on mechanical ventilation, and in-hospital mortality in patients infected with SARS-CoV-2. Methods: a retrospective cohort of ventilated, critically ill patients. We assessed nutrition risk at baseline using NUTRIC-score. Logistic and linear regression models were used to analyze the association between NUTRIC-score and clinical outcomes (days on mechanical ventilation, hospital length of stay, and in-hospital mortality). A survival analysis was performed using Kaplan-Meier curves. Results: a total of 112 patients were included, 39.3 % were overweight and 47.3 % were obese. Based on NUTRIC-Score, 66 % and 34 % of patients were at high and low nutritional risk, respectively. High nutritional risk was associated with increased mortality risk (OR: 2.4, 95 % CI, 1.06-5.47, p = 0.036) and higher 28-day mortality (HR: 2.05, 95 % CI, 1.01-4.23, p = 0.04) in comparison with low risk. Conclusion: high nutritional risk is related to mortality in SARS-CoV-2 critically ill patients. Overweight and obesity are common in this sample. More studies are needed to elucidate the impact of nutritional therapy on infection course and outcomes.

INTRODUCCIÓN: Introducción: el riesgo nutricional se asocia a peores desenlaces en los pacientes en estado crítico. El objetivo de este estudio es describir la asociación entre el riesgo nutricional y los días de estancia hospitalaria, los días de ventilación mecánica y la mortalidad en pacientes infectados por el SARS-CoV-2. Métodos: cohorte retrospectiva de pacientes en estado crítico bajo ventilación mecánica invasiva. Se evaluó el riesgo nutricional utilizando la herramienta NUTRIC-Score. Se utilizaron regresiones lineares y logísticas para evaluar la asociación entre el riesgo nutricional y los desenlaces clínicos (días de ventilación mecánica, días de estancia hospitalaria y mortalidad hospitalaria). Se utilizaron curvas de Kaplan-Meier para analizar la sobrevivencia. Resultados: se incluyeron 112 pacientes, el 39,3 % con diagnóstico de sobrepeso y el 47,3 % con obesidad de acuerdo con el IMC. Utilizando la herramienta NUTRIC-Score, el 66 % tenían riesgo nutricional alto y el 34 % riesgo nutricional bajo. El riesgo nutricional alto se asoció a un mayor riesgo de mortalidad (OR: 2,4; IC 95 %: 1,06-5,47; p = 0,036) y mayor mortalidad a 28 días (HR: 2,05; IC 95 %: 1,01-4,23; p = 0,04) en comparación con los individuos con riesgo nutricional bajo. Conclusión: el riesgo nutricional alto se asocia con mortalidad en los pacientes con infección por SARS-CoV-2 en estado crítico. El sobrepeso y la obesidad son comunes en este grupo de pacientes. Se necesitan más estudios que evalúen el impacto de la terapia nutricional sobre el curso de la infección y los desenlaces clínicos.

Safety and tolerance of enteral nutrition in COVID-19 critically ill patients, a retrospective study.

BACKGROUND: There is a lack of evidence about the tolerance of enteral nutrition (EN) in COVID-19 critically ill patients. However, several gastrointestinal manifestations related to COVID-19 have been described. The aims of this study were to analyze the incidence of gastrointestinal intolerance (GI) associated to EN (diarrhea, vomiting, gastroparesis and constipation) and to describe energy/protein provision along with biochemical alterations during the first week of EN. METHODS: A retrospective cohort of COVID-19 critically ill patients under mechanical ventilation. We reported daily enteral nutrition infusion and gastrointestinal manifestations within the first week of intubation and enteral nutrition initiation. RESULTS: Fifty-two patients were included; 40.3% were overweight and 46.2% were obese. During the first 7 days of EN, manifestations of GI intolerance such as vomiting, diarrhea and gastroparesis were present in 18 patients (32.4%). Hypernatremia (39%) was the most frequent electrolyte abnormality. Only Acute Kidney Injury (AKI) diagnosis was associated with a higher energy deficit on day 7. No associations between drug prescription and GI intolerance were observed. On day 4, 94.5% of patients were receiving more than 80% of energy requirements and 94.2% of protein requirements. Accumulated energy and protein deficits at day 3 were 2171.2 ± 945 kcal and 114.9 ± 49.2 g, respectively; and 2586.4 ± 1151 kcal, 133.3 ± 60.4 g at day 7. CONCLUSION: Enteral nutrition is feasible and well-tolerated in COVID-19 patients with mechanical ventilation within the first week of enteral nutrition initiation. More studies are needed to elucidate the impact of nutritional therapy on infection course and outcomes.

[Modification to surgical technique of cesarean hysterectomy]. / Modificación a la técnica quirúrgica de cesárea-histerectomía.

BACKGROUND: Bleeding is a significant cause of maternal mortality in the world. Obstetric hysterectomy increases maternal morbidity and mortality. OBJECTIVES: To describe a modified technique of cesarean-hysterectomy to limit bleeding during surgery in cases of placenta accreta and placenta previa, which consist of hypogastric artery ligation before the removal of the uterus. Another objective of this study is to compare maternal outcomes of patients undergoing this technique with the usual technique. PATIENTS AND METHOD: Comparative, longitudinal, closed stydy. We analyzed the records of 86 patients undergoing cesarean-hysterectomy surgery, from July 1, 2008 to July 31, 2009, were programmed 29 patients with the modified technique and 57 with the usual. The main outcomes analyzed were: estimated bleeding during surgery, number of packed red blood cells and plasma units transfused and hospital stay in intensive care. RESULTS: Bleeding during surgery, blood transfusion and admission to intensive care demand, and hospital stay were significantly lower in patients with the modified technique. Also there were fewer trans and postoperative complications in this group. CONCLUSIONS: The results of this study show that the modified technique of cesarean-hysterectomy derives significant reduction of maternal morbidity, less massive transfusions demand to manage intensive care units.

Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America.

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS), which activates and joins the lysin with its corresponding transfer RNA (tRNA) through the ATP-dependent aminoacylation of the amino acid. KARS gene mutations have been linked to diverse neurologic phenotypes, such as neurosensorial hearing loss, leukodystrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene and, in addition to the case report, the paper reviews the literature for other cases of KARS1-associated leukodystrophy.

Trends in Cervical Cancer Mortality in Brazilian Women who are Screened and Not Screened.

OBJECTIVE: This study aimed to analyze the trend in cervical cancer (ICD C53) mortality in Brazilian regions in women who are who are screened and not screened from 1996 to 2015. METHODS: An epidemiological study, of time series of mortality from cervical cancer performed in 90,856 women under 24 years old (343 women), between 25 and 64 years old (32,703 women), and over 65 years old (10,909 women). The data from this research were collected from the DATASUS, from the SIM Health Surveillance Secretariat files, captured through TABNET selecting the resident population by gender and age group and ICD 10 C53 from 1996 to 2015. RESULTS: Among women, 43.8% were white, and 76% had less than eight years of formal education. Polynomial regression showed an increasing trend in cervical cancer mortality in Brazil for women aged 15 - 24 years (p=0.01). Between 25 - 64 and 65 years or older it remained constant, but high (p=0.07; 0.99). The Northeast region pointed a growing trend in women aged 15 to 24 (p=0.01), 25 to 64 years (p=0.01) and 65 or older (p=0.001). The Northeast presented the highest average growth per year. In the Southeast, South and Midwest regions, decreasing trends were observed despite the high rates. The Joinpoint regression showed a 95% confidence interval, and that mortality from cervical cancer in the North region increased throughout the period analyzed. an increasing trend was observed from 1996 to 1998, whereas in the Midwest region, the trend remained stable throughout the period analyzed. The Federal District presented an upward trend from 1996 to 2015. In Brazil, an upward trend was observed throughout the whole period analyzed. CONCLUSIONS: Cervical cancer mortality in younger women is becoming more predominant, in addition to the high rate observed for women aged 65 or older. 
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Resting energy expenditure in HIV/AIDS patients: Development and validation of a predictive equation.

BACKGROUND: Accurate measurements of resting energy expenditure (REE) are important for determining nutritional needs in HIV patients. Indirect calorimetry (IC) is a noninvasive method that reflects REE but can be costly and is frequently calculated with predictive equations. Research suggests that REE obtained by predictive equations in people living with HIV/AIDS (PLWH) is inaccurate. The aim of the study is to develop and validate a new predictive equation of REE based on a population of PLWH. METHODS: Cross-sectional study including 164 PLWH (82 to develop and 82 to validate the equation). Multiple linear regression was used to determine the relationship between variables and to develop the new predictive equation. Intraclass correlation coefficient (ICC) and Bland-Altman methods were used to evaluate agreement between the new predictive equation and indirect calorimetry. RESULTS: A new predictive equation with an accuracy of 67% when compared with IC was developed. This equation included as covariates: fat free mass, antiretroviral therapy status and age. CONCLUSION: A new equation to predict energy expenditure in PLWH was developed and validated. This formula can be used to estimate REE if IC is not available.

Antioxidant response to cadmium exposure in primary skeletal muscle cells isolated from humans and elephant seals.

Cadmium (Cd) occurs naturally; however, its concentration can increase with anthropogenic activities. Excess Cd increases reactive oxygen species (ROS) production and oxidative damage, which can lead to pathological conditions. Marine mammals accumulate Cd in the liver and the kidney; yet, there are no reports of Cd-associated tissue damage in whales, seals or dolphins. Response to Cd exposure (0-5.0 µM CdCl2 for 1-12 h) was analyzed and compared in primary skeletal muscle cells isolated from northern elephant seals (Mirounga angustirostris) and humans (Homo sapiens). Antioxidant enzyme activities (glutathione S-transferase, glutathione reductase, glutathione peroxidase), glutathione concentration, and protein carbonyl levels (an indicator of oxidative damage) were quantified. Glutathione levels were higher in northern elephant seal than in human cells. Protein carbonyl content in cells exposed to Cd was lower and had a smaller variability range in elephant seals than in humans. Generalized linear models (GLIM) identified Cd exposure and antioxidant defenses as significant contributors to protein carbonyl variability in human but not in elephant seal cells. These results suggest that the previously observed differences in circulating and tissue glutathione levels between marine and terrestrial mammals are maintained under cell culture conditions and that northern elephant seal and human muscle cells respond differently to Cd exposure. The results also suggest that the observed differences could potentially be associated with the protective mechanisms that allow northern elephant seals to tolerate extreme conditions that result in increased ROS generation (e.g. diving, sleep apnea, fasting) with no oxidative damage.