Treatment with Hydroxychloroquine vs Hydroxychloroquine + Nitazoxanide in COVID-19 patients with risk factors for poor prognosis: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To determine the efficacy of Hydroxychloroquine vs. Hydroxychloroquine + Nitazoxanide in reducing the need for invasive mechanical ventilatory support for patients with COVID-19. Hydroxychloroquine is currently being used in multiple trials with varying doses in an attempt to treat COVID-19. Nitazoxanide has powerful antiviral effects and proven efficacy against a range of viruses including SARS and MERS. Dual therapy by combining appropriate doses of these two medications with diverse activities against COVID-19 is expected to be better than monotherapy with hydroxychloroquine. TRIAL DESIGN: This is a single centre, randomized, controlled, single blinded, 2 arm (ratio 1:1) parallel group trial. PARTICIPANTS: 86 COVID-19 positive patients that are being treated at the Health Institute of the State of Mexico (ISEM) in Toluca, State of Mexico will be recruited from May 14 to December 31, 2020. INCLUSION CRITERIA: 1)Age older than 18 years.2)Hospitalised COVID-19 PCR test positive patients.3)Within the first 72 hours after performing the PCR test.4)Presence of risk factors for complications (at least one): over 60 years, history of diabetes mellitus, hypertension, and morbid obesity. EXCLUSION CRITERIA: 1)Patients with corrected QT interval (QTc) greater than 500ms at hospital admission.2)Patients who have inherent contraindications to each drug.3)Patients who are unable to consent.4)Patients who have previously received chloroquine.5)Patients already intubated. Elimination criteria: 1)Patients whose clinical follow-up is lost or who decide not to continue in the study INTERVENTION AND COMPARATOR: The two management alternatives will be: Control - Hydroxychloroquine 200 mg taken orally every 12 hours for 7 days. Dual therapy - Hydroxychloroquine 400 mg taken orally every 12 hours for two days and then 200 mg taken orally every 12 hours for four days + Nitazoxanide 500 mg orally every 6 hours taken with food, for seven days. MAIN OUTCOMES: Primary: Mechanical ventilation requirement assessed at one week. Percentage of COVID-19 positive patients who require mechanical ventilation . All patients will be monitored till hospital discharge or death. RANDOMISATION: Patients will be randomly allocated using allocation papers and opaque sealed envelopes to either receive the placebo or the dual therapy intervention treatment in a 1:1 ratio until we have recruited the required number of patients for each group. BLINDING (MASKING): Trial participants will be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 86 participants will be randomized to each group, with 43 in the control group and 43 in the dual therapy group. TRIAL STATUS: Protocol version: 2, recruitment will begin on May 14 until sample size is reached , with the analysis deadline of December 31st 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341493. Date of trial registration: April 10, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Genetics of Thyroid Disorders.

BACKGROUND: Thyroid diseases are the most common endocrine pathologies second to diabetes. They have been shown to have high genetic impact, and variants in any of the genes involved in the metabolism of thyroid hormones have marked influence on the development of these diseases. AIM: To identify the genes that have been most involved in the development of thyroid pathologies by reviewing the literature with recent relevant articles. MATERIALS AND METHODS: We performed a literature search on the NCBI (National Center for Biotechnology Information) databases, and that of the European Bioinformatics Institute (EMBL-EBI) using keywords related to the topic of interest). RESULTS: Activation of oncogenes such as RAS, BRAF, RET/PTC and the overstimulation of the PI3K/AKT pathway plays an important role in thyroid tumorigenesis. SLC5A5, SLC26A4, TG, TPO, DUOX2, DUOXA2 are related to hypothyroidism. Risk factors for Graves' disease are associated with the presence of HLA-DR3, CTLA4, PTPN22, CD40, IL2RA (CD25), FCRL3, and IL23R. FOXE1 can be associated to hypothyroidism and papillary thyroid cancer. CONCLUSIONS: Thyroid diseases are polygenetic, and while there are sufficient pathways affected by genetic changes, and there is, to our knowledge, no gene that has been found to be specifically causal, and the pathology has been the result of the interaction of many genetic variables such as polymorphisms or mutations.

Identification of metabolic indicators for cardiovascular risk in schoolchildren

Objective: CardioVascular Disease (CVD) is one of the most important causes of death worldwide affecting people at younger ages every year. The purpose of this study was to identify the metabolic indicators for cardiovascular risk factors in primary school students from Mexico and Colombia. Methods: A clinical, prospective, cross-sectional and comparative study was conducted in Mexico and Colombia to contrast anthropometric measurements, biochemical and dietetic determinations and physical activity. Results: The Waist-Hip Ratio (WHR) and the Waist-to-Height Ratio (WtHR) showed significant differences (p≤0.001) between Mexico and Colombia (0.8 ± 0.1 versus 0.5 ± 0.1) and (0.4 ± 0.06 vs. 0.78 ± 0.04) respectively. The Automatic Linear Modeling showed that the main predictors for cholesterol levels were WtHR, MonoUnsaturated Fatty Acids (MUFA) and lipids ingestion. For glucose there were four main predictors: WHR, carbohydrates, MUFA and Saturated Fatty Acids (SFA). For triglycerides the pedictors were Products of Animal Origin (PAO), BMI, waist circumference, lipids and cholesterol ingestion and Mean Arterial Pressure (MAP). The Weight Estimation tests weighted per gender showed that for glucose levels the main determinants were carbohydrates, MUFA and oils; for cholesterol these were MUFA, PUFA and oils; and for LDL the significant variables were proteins, SFA, PAO and sugars; and last, for triglycerides the main variables were BMI, cholesterol and vegetables. Conclusions: Mexico has higher values in almost all items of cardiovascular risk in children, but both countries have significant percentages of obesity and the population free of cardiovascular risk is minimal.

Mexican pregnant women show higher depression and anxiety with rising age and in the case of being single.

BACKGROUND: Pregnancy is an important predisposition period to develop anxiety and depression, with a direct impact on the woman's offspring. The aim of this study was to report the correlation between depression and anxiety in pregnant women and its association with the marital status and age. MATERIALS: A  descriptive, retrospective and cross-sectional study was conducted in the outpatient care of the Psychology Service at the "Mónica Pretelini Sáenz" Maternal Perinatal Hospital (HMPMPS), Toluca, Mexico, from June 2012 to March 2019. As routine, the  Beck Depression Inventory (BDI-II) and the  Beck Anxiety Inventory-Trait (BAIT), were applied to all women seeking attention at the  HMPMPS. Only pregnant patients were selected for this study, with the women referred for the first time to the external Psychology Clinic as inclusion criteria. Pearson's correlation coefficient and the frequency of cases for age, BDI-II, and BAIT were obtained using the IBM SPSS Statistics ® v.23 software. RESULTS: The  study included 2947 pregnant patients with a mean age of 28.6 ± 6.9 years. Of these, 2616 (88.8%) presented with mild anxiety, 269 (9.1%) with moderate, and 62 (2.1%) with severe anxiety. On the other hand, 2149 (72.9%) patients presented with minimal depression, 341 (11.6%) mild depression, 268 (9.1%) moderate depression, and 189 (6.4%) had severe depression. The correlations between age and BDI-II was -0.026 (P = 0.152), between age and BAI was -0.038 (P = 0.037), and between BAIT and BDI-II 0.650 (P ≤ 0.001). CONCLUSIONS: The age group with the highest frequency of depression and anxiety was from 20 to 29 years. The absence of a stable partner represented an important risk factor for anxiety and depression during pregnancy.

Salivary Immunoglobulin Gene Expression in Patients with Caries.

BACKGROUND: Immunoglobulins mediate the host's humoral immune response are expressed in saliva. AIM: To quantify the FcαR, FcγRIIB, and FcαµR gene expression in the saliva of Mexican patients with caries in mixed and permanent dentition. SUBJECTS AND METHODS: This was a comparative cross-sectional study. mRNA was isolated from 200 µL of saliva following the RNA III Tissue Fresh-frozen protocol of the MagNA Pure LC Instrument 2.0 (Roche Diagnostics GmbH, Nederland BV) and the FcαR, FcαµR and FcγRIIB were quantified through TaqMan Assays. RESULTS: One hundred individuals, 50 with mixed dentition and 50 with permanent dentition, were included in the study. Statistically, it was found a significant difference (p = 0.025) in the IgG (FcγRIIB) expression between the studied groups. CONCLUSION: Although we confirmed the existence of FcαR, FcγRIIB and FcαµR gene expression in saliva, only a significant difference in the expression of FcγRIIB between the mixed dentition and permanent dentition was found.

Glycogen Synthase Kinase-3ß (GSK-3ß) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in early childhood. In children with acute lymphoblastic leukemia (ALL), the activity of glycogen synthase kinase (GSK-3ß) has been associated with changes in the transcriptional activity and expression of nuclear factor kappa beta (NFKB) in the mononuclear cells of bone marrow. OBJECTIVES: The aim of the study was to determine the possible role of glycogen synthase kinase 3beta (GSK-3ß) and nuclear factor kappa beta (NFKB) as prognostic variables in pediatric patients with ALL. MATERIAL AND METHODS: This was a descriptive, transversal, and observational study. Bone marrow and blood samples were obtained from 30 children with newly-diagnosed ALL, who were seen at the Hematology-Oncology Service, Hospital para el Niño (HPN), Toluca, Mexico, from 2014‒2015. Anthropometric variables, clinical lab results, immunophenotype and cytogenetic abnormalities were registered. GSK-3ß was evaluated through immunohistochemistry, and NFKB messenger RNA (mRNA) with real-time polymerase chain reaction (qPCR). The cases of ALL were classified into two groups of risk: high and habitual. RESULTS: Thirty patients were included in this study, with a mean age of 7.1 years (range 2‒13 years). Twenty-one were male and 9 female. Employing the morphological classification, 26 patients had type L1 ALL and the remaining 4 patients had type L2 ALL. Abnormal genes were found in 7 (23.33%) patients, ETV-RUNX1 in 3, followed by TCF3-PBX1 (two), STL1-TAL1 (one), and BCR-ABL1 (one). NFKB relative expression levels, in comparison to the GSK-3ß immunohistochemistry results of the bone marrow samples, showed significant differences between positive and negative cases (p = 0.001) and between weak-positive and negative cases (p = 0.002). CONCLUSIONS: These results suggest that GSK-3ß may be a prognostic biomarker in childhood ALL.

Approach to an obstetric prognosis scale: The modified SOFA scale.

BACKGROUND: Severe obstetric morbidity constitutes a serious problem worldwide; however, an effective obstetrical prognosis scale is still missing. OBJECTIVE: To propose a modified Sequential Organ Failure Assessment Score (SOFA) score based on time before reaching specialized medical attention. METHOD: This was an ambispective, descriptive study, including all women treated at the Obstetrical Intensive Care Unit (OICU) of the "Mónica Pretelini Sáenz" Maternal-Perinatal Hospital (HMPMPS), Toluca, Mexico, from June 2009 to June 2013. The patient's SOFA score and clinical evolution were registered daily. A modified obstetrical SOFA scale was constructed adjusting the value of 180 instead of 200 in the punctuation column of 3 for the PaO2/FiO2 ratio and adding a file of disease evolution time with sepsis prior to reaching specialized medical attention. RESULTS: Two hundred thirty two patients, with an average age (SD) of 26.42 (±7.54) years, mean gestational age of 33 (±7.5) weeks were included in the study; 118 suffered from pre-eclampsia, 56 obstetric haemorrhages, 41 eclampsia (25 preceded by pre-eclampsia) and 23, sepsis. ROC curves showed a higher area under the curve (AUC) for the modified SOFA (0.868; p<0.001) than SOFA (0.796; p=0.003), in the prediction of maternal mortality. CONCLUSIONS: The SOFA score, taking into account a lower value for the Kirby index and a threshold time of 12-h with sepsis before getting specialized medical attention, shows a good predictive value for maternal death and could be considered for evaluating the severity of complicated obstetrical patients. FUNDING: None declared.

Asociación de factores de riesgo de preeclampsia en mujeres mexiquenses / Association preeclampsia risk factors in mexiquenses women

Introducción: La preeclampsia es aún uno de los mayores problemas obstétricos en países en vías de desarrollo.Objetivo: Identificar los principales factores de riesgo para desarrollar preeclampsia en mujeres mexiquenses atendidas en el Hospital Materno Perinatal "Mónica Pretelini Sáenz".Material y métodos: Estudio de casos y controles, se incluyeron dos grupos, el grupo A casos (n=138) y el grupo B controles (n=276) con relación caso-control de 1:2.Los criterios de definición para los casos fueron: mujeres con diagnóstico inicial de preeclampsia y que cuenten con las siguientes mediciones: Tensión Arterial Sistólica (TAS)=140 ó Tensión Arterial Diastólica (TAD)=90 mmHg más una de las siguientes: concentración de proteínas en orina de 24 h =300 ó Proteinuria =++. El grupo de controles quedó conformado por mujeres que acudieron al hospital para atención del embarazo sin preeclampsia. Resultados: La media de edad fue de 27.5±8.0 para los casos (grupo A) y 25.3±6.7 para los controles (grupo B) (P<0.01). El tener 1 o más óbitos (P<0.045), las cifras iniciales y finales de TAS y TAD, el índice de masa corporal pregestacional (IMCPG), el peso al final del embarazo, y la hipertensión arterial sistémica crónica (P<0.01) así como el haber padecido preeclampsia en algún embarazo previo fueron estadísticamente significativo (P<0.01) para tener preeclampsia. Conclusiones: En nuestra población, además de los factores de riesgo tradicionales para preeclampsia se agrega el antecedente de óbitos como otro factor de riesgo para padecer preeclampsia.

Introduction: Preeclampsia is still a major obstetric problem in developing countries. Objective: To identify the main risk factors to develop preeclampsia in women from the State of Mexico attended at the Maternal Perinatal Hospital "MónicaPreteliniSáenz". Materials and methods: In this case-control study, two groups were included, group A patients (n = 138) and B controls (n = 276) with a case-control ratio of 1: 2. The criteria for defining cases were women initially diagnosed with preeclampsia and who had the following measurements: Systolic Blood Pressure (SBP) =140 or diastolic blood pressure (DBP) =90 mmHg plus one of the following: =300 protein concentration in a 24-h urine sample or proteinuria = ++. The control group was made up of women attended at the hospital who did not develop preeclampsia. Results: The mean age was 27.5 ± 8.0 years for the cases (group A) and 25.3 ± 6.7 years for controls (group B) (P <0.01). Having 1 or more stillbirth (P <0.045), initial and final measures of SBP and DBP, the pre-pregnancy body mass index (IMCPG), weight in late pregnancy, and chronic hypertension (P <0.01) as well as having had preeclampsia in a previous pregnancy were statistically significant (P <0.01) to have preeclampsia. Conclusions: In our population, in addition to the traditional risk factors for preeclampsia, history of stillbirthswas is another risk factor to develop preeclampsia.

Adherence to Two Methods of Education and Metabolic Control in Type 2 Diabetics.

BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and written information. METHODS: Patients with type 2 diabetes mellitus (T2DM), aged 20-60 years, education level at least of primary school, serum creatinine ≤ 2.5 mg/dl, self-sufficient and HbA1c ≥ 7.1% were allocated in two groups of education, 1) minimal education (MEG) and 2) full education (FEG). The MEG patients followed predefined diet; FEG patients chose the diet by selecting foods from each group in a list of matches, teaching them to count nutrients, kilocalories (kcal) and percentage of nutrients. RESULTS: A follow-up of 31 patients in each group was obtained. The proportion of patients who had initial adherence was 13.33% in the MEG group and 9.67% in the FEG group while, at the end of the study, these percentages were of 73.3% and 58.38% respectively. The final HbA1c decreased in both groups, with or without good adherence. The FEG group had a higher decline in the values of cholesterol (p = 0.036) and LDL (p = 0.002) than the MEG group. CONCLUSION: Education programs in T2DM contribute to a decrease in HbA1c within six months, but an intensive program is more effective in reducing cholesterol and LDL.

Pregnancy Weight Gain Limitation by a Supervised Nutritional Program Influences Placental NF-κB/IKK Complex Expression and Oxidative Stress.

OBJECTIVE: Nuclear factor kappa B (NF-κB) pathway and oxidative stress participate in endothelial dysfunction, which is one of the causes of pre-eclampsia. Among the human antioxidant mechanisms, there are the enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Our aim was to measure NF-κB, its inhibitor (IKK) and oxidative stress in placenta and umbilical cord of pregnant women submitted to a supervised nutritional program. METHODS: TWO GROUPS WERE CONFORMED: A) 14 pregnant women with individualized nutritional counseling, and B) 12 pregnant women without nutritional guidance. NF-κB and IKK were assessed by real time PCR (RT-PCR). Enzymatic activity of CAT, GPx, lipoperoxidation (LPO) and SOD were also evaluated. RESULTS: Pregnant women that followed a supervised nutritional program had lower levels of systolic (p=0.03) and diastolic pressure (p=0.043) although they were heavier than the control group (p=0.048). Among all the women, the Spearman correlation was positive between weight gain and placental NF-κB expression (1, p≤0.01). In the placenta, women with nutritional advice had lower enzymatic activity of GPx (p≤0.038) and showed a tendency of IKK to be higher than in women without a nutritional supervised program. CONCLUSION: A supervised nutritional program in pregnancy offers a proven option to control weight gain, hypertension, NF-κB/IKK complex expression and oxidative stress reactions in the placenta.

Cell Culture Models and Pharmacological Perspective for the Study of Breast Cancer Markers.

Among the most prevalent neoplasias, breast cancer shows an astonishing tendency. Unfortunately this cancer has a high mortality worldwide, requiring sustained management of all actors involved in public health in order to get an early diagnosis and treatment. The methods associated with conventional cytogenetics and molecular cell culture, besides early detection of gene expression patterns associated with cancer susceptibility, have contributed to identify inherited genes and metabolic disorders related to obesity, which are also involved in breast cancer. In any case, a broad study of the above mentioned factors can give a predictive value to support the design of public health models to determine cancer risk in order to decrease the mortality from this disease. (1) Cell cultures offers a wide range of scientific approach for the study of breast cancer, including the analysis of biological function of several compounds in search of increasingly effective treatments with fewer side effects against this malignancy. (2).

Blood manganese levels in patients with hepatic encephalopathy.

PROJECT: Hepatic encephalopathy is an increasingly common disease. Identification of prognosis risk factors in patients with liver damage may lead to preventive actions, towards decreasing its mortality. Manganese (Mn) levels are increased in basal ganglia of patients with hepatic encephalopathy as well as in cases of cirrhotic and liver failure patients. The present is a clinical, prospective, prolective and observational study developed at the Internal Medicine Service from "Dr. Darío Fernández Fierro" General Hospital, ISSSTE, Mexico City. The objective of this work was to report whole blood Mn levels and mortality in encephalopathic patients. PROCEDURE: Consecutive patients over 18 years of age, diagnosed with hepatic encephalopathy were recruited at the emergency room service. An informed consent, signed by their families was collected. Patients' clinical characteristics, biochemical tests of renal function, hemoglobin, glucose, bilirubins and albumin levels were obtained along with a blood sample to analyze Mn. Patients evolution was followed up for 6 months. RESULTS: Blood Mn in patients [median, (range)] [20.5, (10.5-39.5) µg/L] were higher than blood levels from a group of healthy volunteers [7.5, (6.1-12.8) µg/L] (P<0.001). Among 9 patients studied four died, 2 women and 2 men, those patients showed higher (P=0.032) Mn levels [28, (17-39.5) µg/L] than those alive [13.5, (10.5-32) µg/L] after the follow up period. CONCLUSIONS: In this pilot study, Mn blood levels were higher in hepatic encephalopathy that died as consequence of the disease that those that survived in a 6 month follow up period. Blood Mn could be a potential prognosis factor for death in patients with hepatic encephalopathy.

Pressure ulcers: a pilot study for treatment with collagen polyvinylpyrrolidone.

BACKGROUND: Chronic ulcers owing to pressure cause complications with respect to immobilization and develop through limited blood circulation. There are different treatments for these ulcers; nonetheless, the search for an efficient and economical option continues. One choice could be collagen-polyvinylpyrrolidone (clg-pvp). Presence of pressure ulcers in hospitalized patients constitutes a frequent medical problem which is difficult to manage and can be an entry route for infection. Also, restoring the dermic continuity offers a means of improving a patient's quality-of-life. OBJECTIVE: The aim of the study was to analyze whether cicatrization on pressure ulcers presents more rapidly with local cleaning with soap, application of zinc oxide paste and clg-pvp compared with local cleaning with soap, application of zinc oxide paste and placebo (saline solution with polyvinylpyrrolidone). METHODOLOGY: From July 2002 to April 2003 the authors conducted a clinical, comparative, prospective, longitudinal, randomized study. Coded flasks containing either clg-pvp or placebo were designated for patients according to a table of random numbers. The clg-pvp or placebo was applied to each patient's ulcers at a rate of 1.5 ml intradermically at the four equi-spaced points around the ulcer. The nominal diameter of each ulcer was measured at the start of the study and then weekly over a 3-week period. Statistical analysis was carried out using the SPSS (version 10; SPSS Inc., Chicago, IL) software program. RESULTS: The group treated with clg-pvp experienced a reduction in mean ulcer size from 3.4 to 1.41 cm in diameter, whereas in the placebo group the reduction was from 2.9 to 1.58 cm in diameter. Despite the greater diameter reduction in the first group, the lack of a statistically significant difference could have resulted from the short follow-up period and small sample size.