Emerging concepts on the role of epigenetics in the relationships between nutrition and health.

Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet-related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life-long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one-carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age-related chronic disease. Revealing diet-epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life-long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet-pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled 'Nutrition, Epigenetics, Genetics: Impact on Health and Disease'. For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.

Exploring disparities in incidence and mortality rates of breast and gynecologic cancers according to the Human Development Index in the Pan-American region.

OBJECTIVE: To evaluate whether a country's Human Development Index (HDI) can help explain the differences in the country's breast cancer and gynecological cancer incidence and mortality rates in the Pan-American region. STUDY DESIGN: Ecological analysis. METHODS: Pan-American region countries with publicly available data both in GLOBOCAN 2012 and the United Nations Development Report 2012 were included (n = 28). Incidence and mortality rates age-standardized per 100,000 were natural log-transformed for breast cancer, ovarian cancer, corpus uteri cancer, and cervical cancer. The mortality-to-incidence ratio (MIR) was calculated for each site. Pearson's correlation test and a simple linear regression were performed. RESULTS: The HDI showed a positive correlation with breast cancer and ovarian cancer incidence and mortality rates, respectively, and a negative correlation with cervical cancer incidence and mortality rates. The HDI and corpus uteri cancer showed no association. MIR and the HDI showed a negative correlation for all tumor types except ovarian cancer. An increment in 1 HDI unit leads to changes in cancer rates: in breast cancer incidence ß = 4.03 (95% confidence interval [CI] 2.61; 5.45) P < 0.001, breast cancer mortality ß = 1.76 (95% CI 0.32; 3.21) P = 0.019, and breast cancer-MIR ß = -0.705 (95% CI 0.704; 0.706) P < 0.001; in cervical cancer incidence ß = -3.28 (95% CI -4.78; -1.78) P < 0.001, cervical cancer mortality ß = -4.63 (95% CI -6.10; -3.17) P < 0.001, and cervical cancer-MIR ß = -1.35 (95% CI -1.83; -0.87) P < 0.001; in ovarian cancer incidence ß = 3.26 (95% CI 1.78; 4.75) P < 0.001, ovarian cancer mortality ß = 1.82 (95% CI 0.44; 3.20) P = 0.012, and ovarian cancer-MIR ß = 5.10 (95% CI 3.22; 6.97) P < 0.001; in corpus uteri cancer incidence ß = 2.37 (95% CI -0.33; 5.06) P = 0.83, corpus uteri cancer mortality ß = 0.68 (95% CI -2.68; 2.82) P = 0.96, and corpus uteri cancer-MIR ß = -2.30 (95% CI -3.19; -1.40) P < 0.001. CONCLUSIONS: A country's HDI should be considered to understand disparities in breast cancer and gynecological cancer in the Pan-American region.

The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer.

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1.

Overweight and obesity as poor prognostic factors in locally advanced breast cancer patients.

Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09-2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.

A relationship between acute respiratory illnesses and weather.

Weekly data from 7 years (2004-2010) of primary-care counts of acute respiratory illnesses (ARIs) and local weather readings were used to adjust a multivariate time-series vector error correction model with covariates (VECMX). Weather variables were included through a partial least squares index that consisted of weekly minimum temperature (coefficient = - 0·26), weekly median of relative humidity (coefficient = 0·22) and weekly accumulated rainfall (coefficient = 0·5). The VECMX long-term test reported significance for trend (0·01, P = 0·00) and weather index (1·69, P = 0·00). Short-term relationship was influenced by seasonality. The model accounted for 76% of the variability in the series (adj. R 2 = 0·76), and the co-integration diagnostics confirmed its appropriateness. The procedure is easily reproducible by researchers in all climates, can be used to identify relevant weather fluctuations affecting the incidence of ARIs, and could help clarify the influence of contact rates on the spread of these diseases.

Robotic-assisted versus laparoscopic living donor nephrectomy for renal transplantation: a systematic review and meta-analysis.

INTRODUCTION: Renal transplantation remains the definitive treatment for end-stage renal disease. Currently employed minimally invasive techniques include robotic-assisted laparoscopy and laparoscopy. This study aims to determine whether either method provides an advantage. METHODS: Following PRISMA guidelines, a systematic review was conducted. Data were analysed using Review Manager 5.3. RESULTS: A total of 12 studies were included. Operative time and operative bleeding were similar between both approaches, with a mean difference (MD) of 16min (95% confidence interval (CI) -4.06, 37.38; p = 0.11) and 10.44ml (95% CI -43.89, 64.78; p = 0.71), respectively. Robotics had longer warm ischemia time (MD 1.14min; 95% CI 0.65, 1.63; p = 0.00001) but reduced length of stay (LOS) (MD -0.23days; 95% CI -0.45, -0.01; p = 0.04) and pain (MD -1.26 VAS; 95% CI -1.77, 0.75). Similar complication and conversion rates were seen among groups. CONCLUSIONS: Robotic approaches provide a viable alternative to laparoscopic surgery. Operative time, bleeding volumes, complications and conversion rates are similar between both techniques; apparent robotic advantages on LOS and Pain need to be better analysed by future studies.

Stratifying risk outcomes among adult COVID-19 inpatients with high flow oxygen: The R4 score.

BACKGROUND: High flow oxygen therapy (HFO) is a widely used intervention for pulmonary complications. Amid the coronavirus infectious disease 2019 (COVID-19) pandemic, HFO became a popular alternative to conventional oxygen supplementation therapies. Risk stratification tools have been repurposed -and new ones developed- to estimate outcome risks among COVID-19 patients. This study aims to provide a simple risk stratification system to predict invasive mechanical ventilation (IMV) or death among COVID-19 inpatients on HFO. METHODS: Among 529 adult inpatients with COVID-19 pneumonia, we selected unadjusted clinical risk factors for developing the composite endpoint of IMV or death. The risk for the primary outcome by each category was estimated using a Cox proportional hazards model. Bootstrapping was used to validate the results. RESULTS: Age above 62, eGFR under 60 ml/min, room air SpO2 ≤89 % upon admission, history of hypertension, history of diabetes, and any comorbidity (cancer, cardiovascular disease, COPD/ asthma, hypothyroidism, or autoimmune disease) were considered for the score. Each of the six criteria scored 1 point. The score was further simplified into 4 categories: 1) 0 criteria, 2) 1 criterion, 3) 2-3 criteria, and 4) ≥4 criteria. Taking the first category as the reference, risk estimates for the primary endpoint were HR; 2.94 [1.67 - 5.26], 4.08 [2.63 - 7.05], and 6.63 [3.74 - 11.77], respectively. In ROC analysis, the AUC for the model was 0.72. CONCLUSIONS: Our score uses simple criteria to estimate the risk for IMV or death among COVID-19 inpatients with HFO. Higher category reflects consistent increases in risk for the endpoint.

mTOR inhibitors in the management of hormone receptor-positive breast cancer: the latest evidence and future directions.

BACKGROUND: There is an unmet therapeutic need in endocrine-resistant, hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (BC). Preclinical studies support the hypothesis that the mammalian target of rapamycin (mTOR) inhibition could potentially overcome resistance to endocrine therapy. MATERIALS AND METHODS: A literature review regarding BC and mTOR inhibitors was undertaken. The reference lists from retrieved manuscripts were reviewed to identify further studies. RESULTS: Phase II studies have reported that the combination of mTOR inhibitors with endocrine therapy shows efficacy in patients with advanced disease that progressed after treatment with aromatase inhibitors. The recent findings of the phase III BOLERO-2 confirmed that everolimus in combination with exemestane significantly improved progression-free survival and response rate, with a manageable safety profile. CONCLUSIONS: The addition of everolimus to exemestane for women with HR-positive metastatic BC is now considered a new therapeutic strategy. However, a word of caution should be added regarding toxic effects, which might limit practical use and compliance. It is essential that clinicians are educated about key recommendations for toxicity management and specific guideline dose modifications. Additional research efforts with the addition of these compounds in the early-stage setting is greatly needed to improve the survival of patients with HR-positive BC.

Rheology and DWS microrheology of concentrated suspensions of the semiflexible filamentous fd virus.

Microrheology measurements were performed on suspensions of bacteriophage fd with diffusive wave spectroscopy in the concentrated regime, at different values of ionic strength. Viscosity vs. shear rate was also measured, and the effect of bacteriophage concentration and salt addition on shear thinning was determined, as well as on the peaks in the viscosity vs. shear curves corresponding to a transition from tumbling to wagging flow. The influence of concentration and salt addition on the mean square displacement of microspheres embedded in the suspensions was determined, as well as on their viscoelastic moduli up to high angular frequencies. Our results were compared with another microrheology technique previously reported where the power spectral density of thermal fluctuations of embedded micron-sized particles was evaluated. Although both results in general agree, the diffusive wave spectroscopy results are much less noisy and can reach larger frequencies. A comparison was made between measured and calculated shear modulus. Calculations were made employing the theory for highly entangled isotropic solutions of semiflexible polymers using a tube model, where various ways of calculating the needed parameters were used. Although some features are captured by the model, it is far from the experimental results mainly at high frequencies.

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Blood transfusion in children at a university hospital in a middle-income country: The need to reinforce adherence to current guidelines.

OBJECTIVES: Blood component transfusion is a common procedure used during hospital admissions; however, it is not risk-free. The evaluation of correct use of blood products (BP) is of vast importance considering the risks and costs implied in their use. Our principal objective was to evaluate the adherence to national guidelines for blood transfusion in pediatric patients at a third level university hospital. MATERIAL AND METHODS: A prospective and retrospective descriptive analytical study was conducted to report the incidence of incorrect use of BP in pediatric patients (1 month to 16 years of age). In a timeline period of 4 years, 579 medical records were randomly selected from a total of 6575 transfusions realized to create a statistically significant sample. The variables studied were volume, infusion time, and transfusion criteria. Indications were evaluated in patient's medical records according to national guidelines. RESULTS: Of the transfusions analyzed, 54% were classified as incorrect mainly due to lack of transfusion criteria fulfillment. Blood transfusion indications in pediatric patients adhered poorly to national guidelines. CONCLUSION: The implementation of effective programs for education and information on the use of BP are needed to increase compliance with current guidelines.

[Hepcidin and Plasmodium falciparum malaria in anemic school children in Mali]. / Hepcidine et infection due a Plasmodium falciparum chez un groupe d'ecoliers anémiés du Mali.

Hepcidin is a peptide produced by hepatocytes and detectable in blood and urine. Urinary hepcidin excretion appeared to be significantly increasing in humans with acute and chronic infections or inflammatory diseases. However, the effects of common tropical parasitic infections on hepcidin have not been sufficiently examined. We carried out a study in school children from Mali living in a neighborhood where Plasmodium falciparum malaria and Schistosoma haematobium infections are prevalent. Anemia (hemoglobin < 120 g/l) prevalence was very high among these children (68%); 24% had iron deficiency anemia. The prevalence of infections was also high (65% had at least one infection and 41% had C-reactive protein (CRP) levels > 10 mg/L). S. haematobium was diagnosed in 64%. We assessed first morning urine hepcidin excretion in a sub-sample of 15 children with either S. haematobium, P. falciparum malaria or none; 14 of these 15 children were included in the analyses. Children with P. falciparum malaria excreted significantly higher levels of hepcidin than those with S. haematobium (chi2 = 3.86; p = 0.05) or without any infection (chi2 = 5.95; p = 0.01). Urinary hepcidin correlated significantly with CRP (Spearman's r = 0.59; p = 0.001) and serum ferritin (Spearman's r = 0.73; p = 0.003). Our study confirms the still limited evidence of an association between human malaria and increased urinary hepcidin and points out the need for further studies to define the contribution of hepcidin to anemia associated with this disease.

[WHO growth standards for infants and young children]. / Les standards de croissance de l'Organisation mondiale de la santé pour les nourrissons et les jeunes enfants.

The growth pattern of healthy breastfed infants deviates to a significant extent from the NCHS/WHO international reference. In particular, this reference is inadequate because it is based on predominantly formula-fed infants, as are most national growth charts in use today. The WHO multicentre growth reference study (MGRS), aimed at describing the growth of healthy breastfed infants living in good hygiene conditions, was conducted between 1997 and 2003 in 6 countries from diverse geographical regions: Brazil, Ghana, India, Norway, Oman and the United States. The study combined a longitudinal follow-up of 882 infants from birth to 24 months with a cross-sectional component of 6669 children aged 18-71 months. In the longitudinal follow-up study, mothers and newborns were enrolled at birth and visited at home a total of 21 times at weeks 1, 2, 4 and 6; monthly from 2-12 months; and bimonthly in the 2nd year. The study populations lived in socioeconomic conditions favorable to growth. The individual inclusion criteria for the longitudinal component were: no known health or environmental constraints to growth, mothers willing to follow MGRS feeding recommendations (i.e., exclusive or predominant breastfeeding for at least 4 months, introduction of complementary foods by 6 months of age and continued breastfeeding to at least 12 months of age), no maternal smoking before and after delivery, single-term birth and absence of significant morbidity. Term low-birth-weight infants were not excluded. The eligibility criteria for the cross-sectional component were the same as those for the longitudinal component with the exception of infant feeding practices. A minimum of 3 months of any breastfeeding was required for participants in the study's cross-sectional component. Weight-for-age, length/height-for-age, weight-for-length/height and body mass index-for-age percentile and Z-score values were generated for boys and girls aged 0-60 months. The full set of tables and charts is presented on the WHO website (www.who.int/childgrowth/en), together with tools such as software and training materials that facilitate their application. The WHO child growth standards were derived from children who were raised in environments that minimized constraints to growth, such as poor diets and infection. In addition, their mothers followed healthy practices such as breastfeeding their children and not smoking during and after pregnancy. The standards depict normal human growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socioeconomic status and type of feeding. The standards explicitly identify breastfeeding as the biological norm and establish the breastfed child as the normative model for growth and development. They have the potential to significantly strengthen health policies and public support for breastfeeding. The pooled sample from the 6 participating countries allowed the development of a truly international reference that underscores the fact that child populations grow similarly across the world's major regions when their health and care needs are met. It also provides a tool that is timely and appropriate for the ethnic diversity seen within countries and the evolution toward increasingly multiracial societies in the Americas and Europe as elsewhere in the world. The WHO standards provide a better tool to monitor the rapid and changing rate of growth in early infancy. They also demonstrate that healthy children from around the world who are raised in healthy environments and follow recommended feeding practices have strikingly similar patterns of growth.

Breastfeeding's protection against illness-induced anorexia is mediated partially by docosahexaenoic acid.

OBJECTIVE: To test whether breastfeeding's protection against anorectic responses to infection is mediated by n-3 fatty acids' attenuation of interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha. DESIGN: Experimental and observational studies. SETTING: A hospital-based study was conducted. SUBJECTS: Five groups of infants were followed; three in the experimental and two in the observational study. METHODS: Breast-fed- (BF-1), DHA-supplemented formula- (SFF-1), and non-DHA-supplemented formula-fed (FF-1) infants were studied before and after immunization against diphtheria, tetanus, pertussis and haemophilus influenzae type b. Pre- and post-immunization energy intakes (EI) and serum IL-1beta and TNFalpha were measured. The two other groups, breast-fed (BF-2) and formula-fed (FF-2) infants with pneumonia were followed throughout hospitalization. EI, IL-1beta and TNFalpha were measured at admission and discharge. Baseline erythrocyte fatty acid contents were determined. RESULTS: Both cytokines increased following immunization in all feeding groups. Post-immunization reductions in EI of SFF-1 infants (-11.8+/-5%, CI(95)=-23.3, 1.4%, P=0.07) were intermediate to those observed in BF-1 (-5.2+/-4.2%, CI(95)=-15.2, 5.9%, P=0.27) and FF-1 infants (-18+/-4.4%, CI(95)=-29%, -5.4%, P=0.02). In the observational study, TNFalpha (17.2+/-8.3 vs 3.4+/-3.0 ng/l, P=0.001) and decreases in EI (-31+/-43 vs -15+/-31%, CI(95)=-34%, 0.001%, P=0.056) were greater in FF-2 than in BF-2 infants at admission. Breastfeeding duration was associated positively with docosahexaenoic acid (DHA) erythrocyte contents, and negatively with admission TNFalpha. Decreases in EIs were associated with IL-1beta and TNFalpha concentrations. CONCLUSION: Reductions in EI following immunologic or infectious stimuli were associated with increases in IL-1beta and TNFalpha. Those reductions were attenuated by breastfeeding, and mediated in part by tissue DHA.

Antimicrobial Activity of a Cationic Guanidine Compound against Two Pathogenic Oral Bacteria.

This study evaluated the potential antimicrobial properties of a polyguanidine (CatDex) on two oral bacteria. Chlorhexidine gluconate 1340 µmoL L-1 (CHX 0.12%) was used as control. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) were grown in BHI media. Bacterial sensitivity and antimicrobial activity were determined by the minimum inhibitory concentration (MIC) and Kirby-Bauer methods. To study side effects, that is, toxicity, dental pulp stem cells (DPSCs) were used. Fluorometric cytotoxicity and confocal microscopy assays were used in order to test cell viability. CatDex inhibited growth of S. mutans at all concentrations and growth of P. gingivalis at all concentrations except 25 µmoL L-1. The MIC of CatDex was 50 µmoL L-1 for both S. mutans and P. gingivalis. The inhibition of bacteria exposed for 8 h at 50 µmoL L-1 of CatDex exhibited increased antimicrobial activity over time, with 91% inhibition in both bacteria. The antimicrobial activities of CatDex and CHX were similar when tested on two common bacteria. CatDex was significantly less toxic to DPSCs. CatDex toxicity depended on time and not on concentration. With regard to clinical relevance, CatDex may have potential as a novel antimicrobial agent. Further studies are in progress.

Severe COVID-19 patients have severe vitamin D deficiency in Northeast Mexico / Los pacientes graves con COVID-19 tienen deficiencia grave de vitamina D en el noreste de México

Objective: the association between vitamin D and COVID-19 severity is not consistent. We compared prevalences and analyzed the association between vitamin D deficiency and COVID-19 severity in Northeast Mexico. Methods: this was a cross-sectional study with individuals consecutively included at a referral diagnostic center during March-September 2020 (n = 181). Concurrently, every patient admitted to intensive care was also consecutively included (n = 116). Serum 25(OH)D < 20 ng/mL was considered vitamin D deficiency. Descriptive, ANOVA, and multivariate ordinal regression analyses were performed. Results: vitamin D deficiency prevalence was 63.8 % (95 % CI, 54.7, 72.0) in severe COVID-19; 25.6 % (95 % CI, 17.4, 36.0) in mild COVID-19; and 42.4 % (95 % CI, 33.2, 52.3) in non-diseased individuals. Vitamin D deficiency increased 5 times the odds of severe COVID-19 (95 % CI, 1.1, 24.3), independently of sex, age, body mass index, and inflammatory markers. Conclusions: this study is the first report of vitamin D deficiency in Northeast Mexico. Vitamin D deficiency was associated with COVID-19 severity (AU)

Objetivo: la asociación entre la vitamina D y la gravedad de la COVID-19 no es consistente. Se comparó la prevalencia y se analizó la asociación de la deficiencia de vitamina D con la gravedad de los pacientes con COVID-19 en el noreste de México. Métodos: este fue un estudio transversal. Se incluyó consecutivamente a individuos de un centro de diagnóstico de referencia durante marzo-septiembre de 2020 (n = 181). Paralelamente, se reclutó a todos los pacientes que ingresaron a cuidados intensivos en ese mismo periodo (n = 116). Se consideró que había deficiencia de vitamina D ante cifras de 25(OH)D sérica < 20 ng/ml. Se realizaron un análisis descriptivo, un ANOVA y una regresión ordinal multivariante. Resultados: la prevalencia de la deficiencia de vitamina D fue del 63,8 % (IC del 95 %: 54,7; 72,0) en la COVID-19 grave, del 25,6 % (IC del 95 %: 17,4; 36,0) en la COVID-19 leve y del 42,4 % (IC del 95 %: 33,2; 52,3) sin COVID-19. La deficiencia aumentó 5 veces las probabilidades de una COVID-19 grave (IC del 95 %: 1,1; 23,9) independientemente del sexo, la edad, el índice de masa corporal y los marcadores inflamatorios. Conclusiones: este estudio es el primer informe de la deficiencia de vitamina D en el noreste de México. La deficiencia de vitamina D se asoció con la gravedad de la COVID-19 (AU)

Pattern formation and morphology evolution in Langmuir monolayers.

We present a study of how patterns formed by Langmuir monolayer domains of a stable phase, usually solid or liquid condensed, propagate into a metastable one, usually liquid expanded. During this propagation, the interface between the two phases moves as the metastable phase is transformed into the more stable one. The interface becomes unstable and forms patterns as a result of the competition between a chemical potential gradient that destabilizes the interface on one hand and line tension that stabilizes the interface on the other. During domain growth, we found a morphology transition from tip splitting to side branching; doublons were also found. These morphological features were observed with Brewster angle microscopy in three different monolayers at the water/air interface: dioctadecylamine, ethyl palmitate, and ethyl stearate. In addition, we observed the onset of the instability in round domains when an abrupt lateral pressure jump is made on the monolayer. Frequency histograms of unstable wavelengths are consistent with the linear-instability dispersion relation of classical free-boundary models. For the case of dendritic morphologies, we measured the radius of the dendrite tip as a function of the dendrite length as well as the spacing of the side branches along a dendrite. Finally, a possible explanation of why Langmuir monolayers present this kind of nonequilibrium growth patterns is presented. In the steady state, the growth behavior is determined by Laplace's equation in the particle density with specific boundary conditions. These equations are equivalent to those used in the theory of morphology diagrams for two-dimensional diffusional growth, where morphological transitions of the kind observed here have been predicted.

Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial.

AIMS: The purpose of this study was to identify the effect of pentoxifylline on the urinary protein excretion profile in type 2 diabetic patients. METHODS: 40 type 2 nonhypertensive diabetic patients were randomly allocated to receive either pentoxifylline 400 mg t.i.d. or placebo daily for 16 weeks. Eligible subjects were those with urinary albumin excretion between 20 and 200 microg/min. Subjects receiving angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium antagonists, and diuretics as well as those with reduced renal function, pregnancy, urinary tract infection, and smoking were not included. A 6-month pretreatment stabilization phase aimed to reduce and stabilize fasting serum glucose levels was carried out. Urinary proteins were identified by electrophoresis, and immunodetection was identified by Western blot. Electrophoretic analysis was performed using molecular weight markers of 150, 132, 77, and 66 kDa to identify high-weight proteins, and 54, 41, 36, 27, 21, 14.3, and 12 kDa to identify low-weight proteins. RESULTS: At baseline, subjects in both groups who showed a glomerular tubular pattern did not differ in their urinary excretion profile. The urinary proteins identified were immunoglobulin G, ceruloplasmin, transferrin, and albumin (glomerular pattern) as well as alpha1-antitrypsin, alpha1-acid glycoprotein, collagenase inhibitor, alpha1-microglobulin, trypsin inhibitor, lysozyme, and beta2-microglobulin (tubular pattern). Subjects who received pentoxifylline had reduced urinary excretion of high- and low-molecular weight proteins. CONCLUSIONS: Urinary protein excretion in type 2 diabetic subjects shows a mixed, glomerular and tubular, pattern. Pentoxifylline reduces the excretion of both high and low molecular-weight urinary proteins.

Adaptive Partitioning QM/MM Dynamics Simulations for Substrate Uptake, Product Release, and Solvent Exchange.

Combined quantum mechanics/molecular mechanics (QM/MM) plays an important role in multiscale simulations of biological systems including enzymes. The adaptive-partitioning (AP) schemes surpass the conventional QM/MM methods in that they allow the on-the-fly, smooth exchange of particles between QM and MM subsystems in molecular dynamics simulations, leading to a seamless and dynamic integration of the QM and MM realms. Originally developed for simulating ion solvation in bulk solutions, the AP schemes have recently been extended to the treatment of proteins, fostering applications in the simulations of enzymes. The present contribution provides a detailed account of the AP schemes. We delineate the background of the algorithms and their parallel implementation, as well as offer practical advice and examples for their applications in the simulations of biological systems.