New two-dimensional carbon nitride allotrope with 1 : 1 stoichiometry featuring spine-like structures: a structural and electronic DFT-D study.

In this communication the prediction of a two-dimensional carbon nitride allotrope (CN) featuring a 1 : 1 stoichiometry is considered. Calculations were carried out under ambient conditions of pressure and temperature (1 atm, 300 K), to prove its dynamic (phonon) and thermal stability. The novel CN structure contains pentagonal rings (c-C3N2) linked by nitrogen atoms, and separated by holes, whereas the sp3-like C atoms are bonded to isocyano (C[triple bond, length as m-dash]N-) groups projecting out of its surface and resembling spine-like formations. The predicted structure has a calculated indirect bandgap of approximately 2.78 eV (hybrid HSE06 approximation), that is in the range of visible light, and this it might increase its use in the field of photocatalysis.

Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors.

In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen-Bethesda (N-B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII.

Relationship of Frailty, Nutritional Status and Oral Health-Related Quality of Life in Mexico City Nursing Home Residents.

BACKGROUND: We aimed to identify the association among nutritional status, Oral Health-Related Quality of Life (OHRQoL) and frailty, and to estimate the mediation effect of these conditions between age and frailty in a group of Mexico City nursing home residents. METHODS: We conducted a cross-sectional study. Fried's phenotype criteria, Full Mini Nutritional Assessment, and General Oral Health Assessment Index was applied. RESULTS: The participants (n = 286) mean age was 82.4 (± 9.2) years. The prevalence of frailty was 58%, and the prevalence of malnutrition and the risk of malnutrition were 22.7% and 59.5%, respectively. A higher risk of frailty was associated with older age (p = 0.015), sex (women) (p = 0.041), poor nutritional status (p <0.001) and compromised OHRQoL (p <0.001). Approximately 40% of the effect of age on frailty was mediated by nutritional status and OHRQoL (p <0.05). CONCLUSION: A strong association between nutritional status and frailty was observed. Additionally, OHRQoL was associated with frailty. The effect of age on frailty was mediated by OHRQoL and nutritional status. Interventions targeted to improve nutritional status and oral health may contribute to preventing or delaying the onset of frailty.

Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia.

BACKGROUND: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). METHODS: A case-control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. RESULTS: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47-11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20-0.91). CONCLUSION: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Detrimental effect of increasing sugar concentrations on ethanol production from maize or decorticated sorghum mashes fermented with Saccharomyces cerevisiae or Zymomonas mobilis: biofuels and environmental biotechnology.

The efficiency of ethanol fermentation, as affected by grain source (maize and decorticated red sorghum), total sugar concentration (13 or 20° Plato) and type of microorganism (Saccharomyces cerevisiae or Zymomonas mobilis) was studied. Maize mashes yielded 0.32 l ethanol kg(-1) ground grain whereas mashes prepared with decorticated red sorghum produced 0.28 l ethanol kg(-1). Both microorganisms yielded similar amounts of ethanol. However, high-gravity mashes (20° Plato) yielded lower amounts of ethanol compared to counterparts adjusted to 13° Plato (0.28 vs. 0.22 l ethanol kg(-1) ground grains). In decorticated sorghum mashes adjusted to 20° P, Z. mobilis produced 40 ml kg(-1) more ethanol compared to S. cerevisiae. In addition, Z. mobilis had a lower dependency on nitrogenous compounds.

López-Zepeda uterine manipulator: device description and its application in the total laparoscopic hysterectomy.

During the total laparoscopic hysterectomy (TLH) operation, small changes in the uterine and vaginal cuff position, provided by an adequate manipulator, may optimize the attack angles to the vulnerable structures involved during the procedure and facilitate their dissection. The uterine manipulators are effective because they raise the uterus when moving it from one place to another, leaving the fixing elements on tension. The Lopez-Zepeda uterine manipulator exposes all the anatomic structures involved in TLH, especially those in the vulnerable areas. It avoids dissection and mobilization of the bladder and therefore its innervation. It takes the ureter away from the risky area by 4 cm. to 5 cm. decreasing the injury risk. Finally, thanks to its anteflexion and anteversion movement, it puts the posterior culdotomy area further away from the ureter, the rectum and the sigmoid colon.

The Influence of Lifestyle Behaviors on the Incidence of Frailty.

BACKGROUND: Frailty is a clinical state defined as an increase in an individual's vulnerability to developing adverse health-related outcomes. OBJECTIVES: We propose that healthy behaviors could lower the incidence of frailty. The aim is to describe the association between healthy behaviors (physical activity, vaccination, tobacco use, and cancer screening) and the incidence of frailty. DESIGN: This is a secondary longitudinal analysis of the Mexican Health and Aging Study (MHAS) cohort. SETTING: MHAS is a population-based cohort, of community-dwelling Mexican older adults. With five assessments currently available, for purposes of this work, 2012 and 2015 waves were used. PARTICIPANTS: A total of 6,087 individuals 50-year or older were included. MEASUREMENTS: Frailty was defined using a 39-item frailty index. Healthy behaviors were assessed with questions available in MHAS. Individuals without frailty in 2012 were followed-up three years in order to determine their frailty incidence, and its association with healthy behaviors. Multivariate logistic regression models were used to assess the odds of frailty occurring according to the four health-related behaviors mentioned above. RESULTS: At baseline (2012), 55.2% of the subjects were male, the mean age was 62.2 (SD ± 8.5) years old. The overall incidence (2015) of frailty was 37.8%. Older adults physically active had a lower incidence of frailty (48.9% vs. 42.2%, p< 0.0001). Of the activities assessed in the adjusted multivariate models, physical activity was the only variable that was independently associated with a lower risk of frailty (odds ratio: 0.79, 95% confidence interval 0.71-0.88, p< 0.001). CONCLUSIONS: Physically active older adults had a lower 3-year incidence of frailty even after adjusting for confounding variables. Increasing physical activity could therefore represent a strategy for reducing the incidence of frailty. Other so-called healthy behaviors were not associated with incident frailty, however there is still uncertainty on the interpretation of those results.

Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome.

BACKGROUND: For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. METHODS: Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in children with AL and with acute lymphoblastic leukaemia (ALL) and also in children < or = 6 and >6 years old. RESULTS: Breastfeeding and early infections showed moderate (but not significant) association for AL, whereas hospitalisation by infection during the first year of life increased the risk: odds ratios (confidence interval 95%) were 0.84 (0.43-1.61), 1.70 (0.82-3.52); and 3.57 (1.59-8.05), respectively. A similar result was obtained when only ALL was analysed. CONCLUSION: We found that breastfeeding was a protective factor for developing AL and ALL, and during the first year of life, infections requiring hospitalisation were related to a risk for developing the disease in those children with DS >6 years of age. These data do not support the Greaves's hypothesis of early infection being protective for developing ALL.

Allostatic Load as a Biological Substrate to Intrinsic Capacity: A Secondary Analysis of CRELES.

OBJECTIVES: Intrinsic capacity (IC) is one of the latest views of positive aging. In its current status lacks a biological substrate amenable to be intervened. The aim of this study was to determine the association of allostatic load (AL) with IC. DESIGN: We present a cross-sectional analysis of the Costa Rican Longevity and Healthy Aging Study. SETTING: This report is from a representative sample of Costa Rican older adults; one of the countries that integrate the Central America region. PARTICIPANTS: 2,827, 60-year or older community-dwelling individuals. METHODS: An IC index was gathered and validated, including different domains: cognitive, psychological, sensory, vitality and locomotion. AL was integrated with: blood pressure, abdominal obesity, body mass index, HDL-cholesterol, glycosylated hemoglobin, DHEAS, cortisol, epinephrine and norepinephrine. AL was grouped in three categories according to the number of abnormal biomarkers (0-1, 2-3 and ≥4). Chronic diseases, socioeconomic level, sex and age were the adjusting variables. Ordinal logistic regression models were estimated in order to test the strength of the association. RESULTS: From a total sample of 1,888 individuals, 51% (n=962) were women, 36.4% were in the 60-69 age category. The mean score of the IC index was of 6.6 (±2.2). Odds ratio (OR) of the adjusted models were significant for the group of those with 2-3 abnormal biomarkers of AL (OR 0.67, p=0.007) and also for those with ≥4 (OR 0.56, p=0.002), when compared to the reference group of AL (0-1 abnormal biomarkers). CONCLUSIONS AND IMPLICATIONS: AL showed an incremental association with IC, even when adjusted for factors such as socioeconomic status and chronic diseases. Targeting therapeutically AL could potentially improve IC in older adults and therefore decreasing the progression to disability or to overt dependency.

Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms.

Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as FN1, APP, CREBBP, EGFR playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and -18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.

Expression of the cystic fibrosis gene in adult human lung.

Critical to an understanding of the pulmonary disease in cystic fibrosis (CF) and the development of effective gene therapies is a definition of the distribution and regulation of CF gene expression in adult human lung. Previous studies have detected the product of the CF gene, the CF transmembrane conductance regulator (CFTR), in submucosal glands of human bronchi. In this report, we have characterized the distribution of CFTR RNA and protein in the distal airway and alveoli of human lungs. Samples from eight human lungs were analyzed for CFTR expression by in situ hybridization and immunocytochemistry. CFTR was detected in a subpopulation of epithelial cells at every level of the distal lung, including proximal, terminal, and respiratory bronchioles, and the alveoli. However, there was substantial variation in the level of CFTR expression between samples. In bronchioles, CFTR protein localized to the apical plasma membrane and was found primarily in a subpopulation of nonciliated cells. CFTR was expressed in the same distribution as the Clara cell marker CC10 in proximal bronchioles, however, expression was discordant in the more distal bronchioles and alveoli where CC10 was not detected. These studies suggest that epithelial cells of the distal lung may play a primary role in the pathogenesis of CF as well as expand the spectrum of target cells that should be considered in the development of gene therapies.

Validity of Knee-Estimated Height to Assess Standing Height in Older Adults: A Secondary Longitudinal Analysis of the Mexican Health and Aging Study.

OBJECTIVE: The main objective was to test the validity of height estimated by knee height in Mexican older adults, as a surrogate for standing height. DESIGN: Cohort study. SETTING: Data were drawn from the first and third waves of the Mexican Health and Aging Study. PARTICIPANTS: Included participants were community-dwelling 50-year or older adults with measured height at baseline and in follow-up. Subjects with a lower limb fracture in the follow-up were excluded. MEASUREMENTS: Main measurements were baseline standing height and 11-year follow-up and knee-estimated height in follow-up. Population specific equations were used to estimate standing height from knee height. Comparisons between baseline standing height and knee-derived height were done with simple correlations, limits of agreement (Bland-Altman plot) and Deming regressions. RESULTS: A total of 136 50-year or older adults were followed-up for eleven years, with a mean age of 60. There was a positive correlation between knee-estimated height and baseline standing height of 0.895 (p<0.001) for men and of 0.845 (p<0.001) for women. Limits of agreement for men were from -6.95cm to 7.09cm and for women from -6.58cm to 8.44cm. CONCLUSION: According to our results, knee-estimated height could be used interchangeably with standing height in Mexican older adults, and these results might apply also to other populations.

TWO-WAY Bridge between Muscular Dysfunction and Cognitive Impairment: Secondary Analyses of SABE - Bogota Study.

BACKGROUND AND OBJECTIVE: Muscular dysfunction and cognitive impairment are both disabling states, affecting especially the elderly. Thus, are important subjects of research. Our goal is to describe the association between these two entities in the elderly. METHODS: This is a secondary analysis from the SABE 2012 Bogota survey, which is a cross-sectional study. We define muscular dysfunction as an abnormal result in gait speed and/or handgrip strength tasks. Cognitive impairment was defined as an abnormal result in Mini Mental State Examination. Other independent variables were measured. RESULTS: A total of 1,564 older adults were included in the analysis. Cognitive impairment showed statistically significant association with both low handgrip strength (OR: 2.25; CI 1.52 - 3.33) and low gait speed (OR: 2.76; CI 1.83 - 4.15) in the adjusted model. CONCLUSION: In older adults, muscular dysfunction is associated with cognitive impairment. New studies should address the causality and temporality of this relationship.

A recombinant human enzyme for enhanced interstitial transport of therapeutics.

Subcutaneously injected therapeutics must pass through the interstitial matrix of the skin in order to reach their intended targets. This complex, three-dimensional structure limits the type and quantity of drugs that can be administered by local injection. Here we found that depolymerization of the viscoelastic component of the interstitial matrix in animal models with a highly purified recombinant human hyaluronidase enzyme (rHuPH20) increased the dispersion of locally injected drugs, across a broad range of molecular weights without tissue distortion. rHuPH20 increased infusion rates and the pattern and extent of appearance of locally injected drugs in systemic blood. In particular, rHuPH20 changed the pharmacokinetic profiles and significantly augmented the absolute bioavailability of locally injected large protein therapeutics. Importantly, within 24 h of injection, the interstitial viscoelastic barriers were restored without histologic alterations or signs of inflammation. rHuPH20 may function as an interstitial delivery enhancing agent capable of increasing the dispersion and bioavailability of coinjected drugs that may enable subcutaneous administration of therapeutics and replace intravenous delivery.

Calf circumference predicts mobility disability: A secondary analysis of the Mexican health and ageing study.

INTRODUCTION: Calf circumference is a surrogate measurement of muscle mass. However, there is scarce evidence on its validity in predicting adverse outcomes such as mobility disability. The aim of this report is to determine if calf circumference could predict incident mobility disability in Mexican 60-year or older adults. METHODS: This is a secondary analysis of the Mexican Health and Aging Study and in particular of its two first waves. Sixty-year or older adults without mobility disability in the first assessment were included and followed-up for two years. Calf circumference quartile groups were compared to test the difference of incident mobility disability. Logistic regression models were fitted to test the independent association when including confounding variables. RESULTS: A total of 745 older adults were assessed, from which 24.4% of the older adults developed mobility disability at follow-up. A calf circumference > 38 cm was associated with a higher risk of developing mobility disability, even after adjustment in the multivariate model, with an odds ratio 0.55 (95% confidence interval 0.31-0.99, P = 0.049). CONCLUSIONS: High calf circumference in Mexican older adults is independently associated with incident mobility disability. This could reflect the impact of adverse health conditions such as obesity (with high fat tissue) or edema. Further research should aim at testing these results in different populations.

Frailty Across Age Groups.

BACKGROUND: The implementation of an aging biomarker into clinical practice is under debate. The Frailty Index is a model of deficit accumulation and has shown to accurately capture frailty in older adults, thus bridging biological with clinical practice. OBJECTIVES: To describe the association of socio-demographic characteristics and the Frailty Index in different age groups (from 20 to over one hundred years) in a representative sample of Mexican subjects. DESIGN: Cross-sectional analysis. SETTING: Nationwide and population-representative survey. PARTICIPANTS: Adults 20-years and older interviewed during the last Mexican National Health and Nutrition Survey (2012). MEASUREMENTS: A 30-item Frailty Index following standard construction was developed. Multi-level regression models were performed to test the associations of the Frailty Index with multiple socio-demographic characteristics across age groups. RESULTS: A total of 29,504 subjects was analyzed. The 30-item Frailty Index showed the highest scores in the older age groups, especially in women. No sociodemographic variable was associated with the Frailty Index in all the studied age groups. However, employment, economic income, and smoking status were more consistently found across age groups. CONCLUSIONS: To our knowledge, this is the first report describing the Frailty Index in a representative large sample of a Latin American country. Increasing age and gender were closely associated with a higher score.

Sarcopenia prevalence using simple measurements and population-based cutoff values.

OBJECTIVE: To estimate the prevalence of sarcopenia in Mexican older adults using simple measurements and tailored cutoff values for the components of the European Working Group on Sarcopenia in Older People algorithm. MATERIAL AND METHODS: This study used cross-sectional data from the third wave (2012) of the Mexican Health and Aging Study. Gait speed and handgrip strength cutoff values were tailored for Mexican older adults. Muscle mass was estimated by a formula, which uses simple anthropometry and demographic characteristics. RESULTS: From the total of 1,238 older adults included in our study, sarcopenia prevalence was 11% (n = 137). When categorizing sarcopenia, 39.1% (n = 484) had pre-sarcopenia, 8.3% (n = 103) moderate sarcopenia, and 2.75% (n = 34) had severe sarcopenia. CONCLUSIONS: Sarcopenia is a common problem in Mexican older adults, and its frequency along with its severity increases with age. Tailored cutoff values could help in identifying those subjects that could have benefited from intervention.

RISK FACTORS FOR SLOW GAIT SPEED: A NESTED CASE-CONTROL SECONDARY ANALYSIS OF THE MEXICAN HEALTH AND AGING STUDY.

BACKGROUND: Physical performance tests play a major role in the geriatric assessment. In particular, gait speed has shown to be useful for predicting adverse outcomes. However, risk factors for slow gait speed (slowness) are not clearly described. OBJECTIVES: To determine risk factors associated with slowness in Mexican older adults. DESIGN: A two-step process was adopted for exploring the antecedent risk factors of slow gait speed. First, the cut-off values for gait speed were determined in a representative sample of Mexican older adults. Then, antecedent risk factors of slow gait speed (defined using the identified cut-points) were explored in a nested, cohort case-control study. SETTING PARTICIPANTS: One representative sample of a cross-sectional survey for the first step and the Mexican Health and Aging Study (a cohort characterized by a 10-year follow-up). MEASUREMENTS: A 4-meter usual gait speed test was conducted. Lowest gender and height-stratified groups were considered as defining slow gait speed. Sociodemographic characteristics, comorbidities, psychological and health-care related variables were explored to find those associated with the subsequent development of slow gait speed. Unadjusted and adjusted logistic regression models were performed. RESULTS: In the final model, age, diabetes, hypertension, and history of fractures were associated with the development of slow gait speed. CONCLUSIONS: Early identification of subjects at risk of developing slow gait speed may halt the path to disability due to the robust association of this physical performance test with functional decline.