How hydrophobicity, side chains, and salt affect the dimensions of disordered proteins.

Despite the generally accepted role of the hydrophobic effect as the driving force for folding, many intrinsically disordered proteins (IDPs), including those with hydrophobic content typical of foldable proteins, behave nearly as self-avoiding random walks (SARWs) under physiological conditions. Here, we tested how temperature and ionic conditions influence the dimensions of the N-terminal domain of pertactin (PNt), an IDP with an amino acid composition typical of folded proteins. While PNt contracts somewhat with temperature, it nevertheless remains expanded over 10-58°C, with a Flory exponent, ν, >0.50. Both low and high ionic strength also produce contraction in PNt, but this contraction is mitigated by reducing charge segregation. With 46% glycine and low hydrophobicity, the reduced form of snow flea anti-freeze protein (red-sfAFP) is unaffected by temperature and ionic strength and persists as a near-SARW, ν ~ 0.54, arguing that the thermal contraction of PNt is due to stronger interactions between hydrophobic side chains. Additionally, red-sfAFP is a proxy for the polypeptide backbone, which has been thought to collapse in water. Increasing the glycine segregation in red-sfAFP had minimal effect on ν. Water remained a good solvent even with 21 consecutive glycine residues (ν > 0.5), and red-sfAFP variants lacked stable backbone hydrogen bonds according to hydrogen exchange. Similarly, changing glycine segregation has little impact on ν in other glycine-rich proteins. These findings underscore the generality that many disordered states can be expanded and unstructured, and that the hydrophobic effect alone is insufficient to drive significant chain collapse for typical protein sequences.

Fit for Purpose Approach To Evaluate Detection of Amino Acid Substitutions in Shotgun Proteomics.

Amino acid substitutions (AASs) alter proteins from their genome-expected sequences. Accumulation of substitutions in proteins underlies numerous diseases and antibiotic mechanisms. Accurate global detection of AASs and their frequencies is crucial for understanding these mechanisms. Shotgun proteomics provides an untargeted method for measuring AASs but introduces biases when extrapolating from the genome to identify AASs. To characterize these biases, we created a "ground-truth" approach using the similarities betweenEscherichia coli and Salmonella typhimurium to model the complexity of AAS detection. Shotgun proteomics on mixed lysates generated libraries representing ∼100,000 peptide-spectra and 4161 peptide sequences with a single AAS and defined stoichiometry. Identifying S. typhimurium peptide-spectra with only the E. coli genome resulted in 64.1% correctly identified library peptides. Specific AASs exhibit variable identification efficiencies. There was no inherent bias from the stoichiometry of the substitutions. Short peptides and AASs localized near peptide termini had poor identification efficiency. We identify a new class of "scissor substitutions" that gain or lose protease cleavage sites. Scissor substitutions also had poor identification efficiency. This ground-truth AAS library reveals various sources of bias, which will guide the application of shotgun proteomics to validate AAS hypotheses.

The experience of women in a phase II trial of hypnosis and progressive muscle relaxation for body image: informing future research questions.

This study examines feedback from two interventions, hypnosis and progressive muscle relaxation (PMR), to improve body image in a randomized phase II trial. Eighty-seven women were randomized either to hypnosis or PMR. Sixty-three women (72%) were motivated to write comments about their study experience. These comments were explored in an unplanned qualitative analysis. Thematic analysis generated five themes, suggesting both hypnosis and PMR may improve body image through the ability to relax and manage stress, sleep better, improve mood and create a mind-body connection. Sexual health emerged as a theme for participants in only the hypnosis group which suggests hypnotic suggestions for body image may improve overall sexual health. Additional research is needed to assess this further.

Análisis de la discapacidad por trastornos musculoesqueléticos en México de 1990 a 2021 / Analysis of musculoskeletal disorders-associated disability in Mexico from 1990 to 2021

Resumen Antecedentes: Los trastornos musculoesqueléticos (TME) afectan a 1710 millones de personas en todo el mundo y es la principal causa de discapacidad. Objetivo: Analizar los años vividos con discapacidad (AVD) por TME en México entre 1990 y 2021. Material y métodos: Con las estimaciones del estudio de la Carga Global de la Enfermedad 2021 se analizaron los AVD por TME y sus seis categorías: osteoartritis, artritis reumatoide, gota, dolor cervical, lumbalgia y otros TME. Se evaluaron patrones y tendencias del número, tasa cruda y tasa estandarizada por edad de los AVD a nivel nacional, estatal, por grupos de edad y sexo. Resultados: Los TME constituyeron la principal causa de AVD en México entre 1990 y 2021, con un incremento de 57.3 %; pasaron de 1458.4 a 2293.7 por 100 000 habitantes. La lumbalgia (840.6 AVD) destacó con la mayor tasa en 2021 y la osteoartritis, con el mayor incremento. Los TME se incrementaron con la edad y, con excepción de la gota, afectaron más a las mujeres. Conclusiones: De 1990 a 2021, los TME constituyeron la principal causa de AVD en México, con mayor impacto en adultos y mujeres. Los TME se evidencian desde edades tempranas, de ahí la necesidad de intervenciones continuas para preservar la calidad de vida.

Abstract Background: Musculoskeletal disorders (MSD) affect 1.71 billion people worldwide and are the leading cause of disability. Objective: To analyze the years lived with disability (YLD) attributed to MSD in Mexico between 1990 and 2021. Material and methods: With estimates from the Global Burden of Disease 2021 study, the YLDs due to MSD and their six categories were analyzed, including osteoarthritis, rheumatoid arthritis, gout, neck pain, low back pain, as well as other MSDs. Patterns and trends in the number, crude rate, and YLD age-standardized rate were evaluated at the national and state levels, as well as by age group and gender. Results: MSDs were the main cause of YLDs in Mexico between 1990 and 2021, with an increase of 57.3%, going from 1,458.4 to 2,293.7 per 100,000 population. Low back pain (840.6 YLD) showed the highest rate in 2021, while osteoarthritis had the largest increase. MSDs increased with age and, and except for gout, affected women more often. Conclusions: From 1990 to 2021, MSDs were the main cause of YLDs in Mexico, with a higher impact on adults and women. MSDs can appear early in life, hence the need for continuous interventions in order to preserve quality of life.

Health and economic impact associated with rheumatoid arthritis discharges: a cost analysis of a two-year cohort in Mexico.

BACKGROUND: Rheumatoid arthritis is a highly prevalent disease. Patients undergo various medical and pharmacological treatments, which have an economic impact on hospitals. The aim of this study was to estimate the direct economic costs of Mexican Social Security Institute (IMSS) resources used to provide healthcare to adult patients with rheumatoid arthritis in 2016-2017. METHODS: Data of patients aged > 18 years with Rheumatoid Arthritis (RA) were obtained from databases and public information sources to estimate the use of IMSS resources for the target population. Total costs were estimated by means of the macro-costing method, employing the diagnosis-related group (DRG). Each DRG of the IMSS was constructed with one of the diagnoses and the respective combination of clinical characteristics included in the ICD-9. This study was conducted from the national perspective of IMSS, the largest healthcare service administrator in the country. As such, it can be considered representative of the broader healthcare landscape in Mexico. RESULTS: The total cost per year of furnishing inpatient care to RA patients was found to be $170,099,794 MXN ($9,096,245.67 USD) for 2016 and $167,039,481 MXN ($8,932,592.57 USD) for 2017, implying an enormous economic impact on the government budget for Mexican public health services. CONCLUSIONS: Our results demonstrate that the direct costs of musculoskeletal and cardiovascular surgery represented the highest costs of RA in-hospital care at IMSS (the largest health institution in Mexico) in 2016 and 2017. Further studies are needed that include the cost of drugs and other indirect costs in addition to our results to get the most accurate approximation of the cost of living with RA.

Characterization of 554 Mexican Patients With Nonsyndromic Cleft Lip and Palate: Descriptive Study.

Orofacial clefts are one of the most common birth defects and the most common craniofacial malformation worldwide. The most common orofacial clefts (OFCs) are congenital cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). The incidence of OFCs varies depending on region and ethnicity; however, it affects approximately 1 in 600 newborns worldwide. In most cases, CL ± P and CP are multifactorial congenital malformations, where both exogenous and genetic factors play an important role. The objective of this study was to describe the frequency of potential risk factors associated with the development of CL ± P and CP in Mexican population. Patients were referred for multisystemic treatment, from private and public institutions in different regions of the country (center, north, and south). Sociodemographic information, prenatal and parental history were obtained through direct interviews with the patients or the patients' mothers in the case of underaged patients. Referred patients were invited to participate in the study. No interventions were applied for this study. The relationship between these factors and the prevalence of CL ± P and CP was studied. A total of 554 patients were included, the majority with CLP (30% to 7%), statistically significant differences were found for folic acid ( P = 0.02) consumption. Familial aggregation did not reach statistical significance for first-degree family members ( P = 0.34) but was significant for second-degree family members ( P = 0.007). More risk factors associated with CL ± P and CP may still be unknown, prompting more epidemiological research and research in other little-studied areas, such as; specific genetic factors in Mexican population.

[Adaptation in Spanish and validation in Mexico of the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP]. / Adaptación en español y validación en México de la herramienta de tamizaje nutricional STAMP (Screening Tool for the Assessment of Malnutrition in Paediatrics).

Introduction: Background: pediatric malnutrition is one of the main causes of complications in hospitalized children. Nutritional screening at admission is essential. The Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) is a simple, reproducible and easy-to-interpret tool, but it is not validated in Mexico. The objective of the study was to validate and adapt the STAMP nutritional screening tool to the Mexican population. Methods: the validation was carried out in two phases: firstly, the translation and cultural adaptation was carried out; and secondly, a cross-sectional study was performed comparing the STAMP tool with a complete nutritional assessment (CNA). A pediatrician specialized in nutrition performed the CNA with the evaluation of anthropometric, clinical and dietary parameters; later, two nutritionists carried out the same evaluation with the STAMP tool. Finally, the patients were graded as low risk and moderate or severe malnutrition risk. Results: of the 300 patients included in the study, 160 were boys (53.3 %) and 140 were girls (46.7 %), with a mean age of 9.44 ± 5.73 years. The assessments made by with the STAMP tool had a 100 % concordance. Compared with CNA, a kappa index of 0.480 (p < 0.01) was obtained. The STAMP test showed a sensitivity of 92 %, a specificity of 75 %, positive predictive value (PPV) of 45 %, negative predictive value (NPV) of 97 %, RVN of 3,68, and RVN of 0,10. Conclusions: the STAMP screening tool has the necessary elements to objectively assess the risk of malnutrition in Mexican children and is a highly sensitive and specific test. test.

Introducción: Antecedentes: la desnutrición pediátrica es una de las principales causas de complicaciones en niños hospitalizados, por ello, el tamizaje nutricional al ingreso es indispensable. La Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) es una herramienta sencilla, reproducible y fácil de interpretar, sin embargo, en México no se encuentra validada. El objetivo del estudio fue validar y adaptar a la población mexicana la herramienta de tamizaje nutricional STAMP. Metodología: la validación se realizó en dos fases: en primer lugar, se realizó la traducción y adaptación cultural; y en segundo lugar, se llevó a cabo un estudio transversal comparando la herramienta STAMP con una evaluación nutricional completa (ENC). Un médico pediatra especialista en nutrición realizó la ENC con la evaluación de parámetros antropométricos, clínicos y dietéticos y, posteriormente, dos nutriólogas realizaron la misma evaluación con la herramienta STAMP. Finalmente, se tamizaron todos los pacientes en leve y moderado o grave riesgo de desnutrición. Resultados: de los 300 pacientes incluidos en el estudio, 160 fueron niños (53,3 %) y 140, niñas (46,7 %), con una media de edad de 9,44 ± 5,73 años. Las valoraciones realizadas con la herramienta STAMP tuvieron una concordancia del 100 %. Comparado con la ENC, se obtuvo un índice kappa de 0,480 (p < 0,01). La prueba STAMP mostró una sensibilidad del 92 %, una especificidad del 75 %, valor predictivo positivo (VPP) del 45 %, valor predictivo negativo (VPN) del 97 %, LR- de 3,68 y LR- de 0,10. Conclusiones: la herramienta de tamizaje STAMP cuenta con los elementos necesarios para evaluar de forma objetiva el riesgo de desnutrición en niños mexicanos y es una prueba altamente sensible y específica.

Stroke Counseling Intervention for Young Adult African Americans: A Randomized Controlled Trial.

BACKGROUND: African Americans have a higher incidence of early-onset stroke and poorer stroke-related outcomes than other race/ethnic groups. OBJECTIVES: Our two-arm, randomized controlled trial was implemented to assess efficacy of the nurse-led Stroke Counseling for Risk Reduction (SCORRE) intervention in reducing stroke risk in young African American adults by improving accuracy of perceived stroke risk and lifestyle behaviors (i.e., diet, physical activity, and smoking cessation). Stroke knowledge, behavior change readiness, and perceived competence to live a healthy lifestyle were also explored as secondary outcomes. METHODS: African Americans aged 20-35 years, recruited from an urban university and surrounding community, were randomized to SCORRE or an attention placebo control group receiving safe sex education. Data were collected pre-intervention, immediate post-intervention, and at 8 weeks. Multilevel models were used for primary outcome analyses. RESULTS: Participants ( n = 106) were mostly in their mid-20s, female, college students, and averaged about three modifiable stroke risk factors. Compared to the control group, participants in the intervention group had, on average, a significant increase in accuracy of perceived stroke risk post-intervention, a greater change in perceived competence to live healthy, and a greater increase in dietary components at 8 weeks. Significant changes were not found in physical activity and other outcomes. DISCUSSION: These findings suggest that SCORRE is a promising intervention to reduce stroke risk among young African American adults. Results will inform a more robust, randomized controlled trial of SCORRE to have an age, culture, and gender-focused intervention that effectively reduces stroke risk among African Americans early in life.

Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: Systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Fatty liver disease is an important public health problem. Early diagnosis is critical to lower its rate of progression to irreversible/terminal stages. This study aimed to evaluate the accuracy of non-invasive prediction scores for fatty liver disease (NAFLD and NASH) diagnosis in adults. MATERIALS AND METHODS: A search was conducted in 10 databases, a qualitative synthesis of 45 studies, and quantitative analysis of the six most common scores. There were 23 risk scores found for NAFLD diagnosis and 32 for NASH diagnosis. The most used were Fatty Liver Index (FLI), aspartate aminotransferase (AST) to Platelet Ratio Index, Fibrosis-4 Index (FIB-4), AST/alanine aminotransferase (ALT) ratio, BARD score, and NAFLD fibrosis score (NFS). RESULTS: The results from the meta-analysis for FLI: Area under the curve (AUC) of 0.76 (95% Confidence Interval [CI] 0.73, 0.80), sensitivity 0.67 (CI 95% 0.62, 0.72) and specificity 0.78 (CI 95% 0.74, 0.83). The AST to Platelet Ratio Index: AUC 0.83 (CI 95% 0.80, 0.86), sensitivity 0.45 (95% CI 0.29, 0.62), and specificity of 0.89 (95% CI 0.83, 0.92). The NFS: AUC of 0.82 (CI 95% 0.78, 0.85), sensitivity 0.30 (CI 95% 0.27, 0.33) and specificity 0.96 (CI 95% 0.95,0.96). CONCLUSIONS: The FLI for NAFLD and AST to Platelet Ratio Index for NASH were the risk scores with the highest prognostic value in the included studies. Further research is needed for the application of new diagnostic risk scores for NAFLD and NASH.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Developing a core outcome set for anthropometric evaluation for presurgical infant orthopaedics for unilateral cleft lip and palate: e-Delphi consensus.

INTRODUCTION: Presurgical infant orthopaedics (PSIO) in infants with cleft lip and palate focuses on improving the anatomical conditions of the lip, palate and nose before the first lip surgery; however, its effectiveness has not been proven. OBJECTIVE: To develop a core outcome set for reporting anthropometry-based outcomes in studies appraising the PSIO before primary cleft lip repair in unilateral cleft lip palate (UCLP). METHOD: Literature search to identify anthropometric measures. The operational definition and schematic representation of each were elaborated, grouping those apparently the same. By using Delphi methodology with a consensus of 10 subject-matter experts, three rounds were conducted to select a core outcome set of anthropometric measures with a validity V coefficient ≥80% among considered necessary to evaluate the PSIO in UCLP. RESULTS: A total of 101 anthropometric measures were identified in the literature to evaluate PSIO in UCLP. Of these, consensus validated the content of the core outcome set, which comprises 18 anthropometric measures, including columella height, nasal tip projection, projection alar length, width of nostril, nasal basal width, angle of columella, cleft lip segment, height of the non-cleft lip, height of the cleft lip, intersegment distance, arch length, greater segment length, lesser segment length, lateral deviation of the incisal point, posterior width of palatal cleft, arch width, grater segment rotation and lesser segment rotation. CONCLUSIONS: Standardised outcome measures are necessary to evaluate and ensure the quality of treatment in CLP. The core outcome set for anthropometric evaluation validated by consensus subject-matter experts is a clinically useful and low-cost tool for PSIO effectiveness studies.

Pharmacogenomic study of anthracycline-induced cardiotoxicity in Mexican pediatric patients.

Background: The aim of this study was to evaluate the association between well-defined genetic risk variants in SLC28A3, RARG and UGT1A6 and anthracycline-induced cardiotoxicity in Mexican pediatric patients. Methods: We tested a cohort of 79 children treated with anthracyclines for the presence of SLC28A3-rs7853758, RARG-rs2229774 and UGT1A6-rs17863783. Results: The SLC28A3-rs7853758 variant was more frequent in this cohort, while the UGT1A6-rs17863783 and RARG-rs2229774 variants were present at lower frequencies. A clinically important decrease of fractional shortening was associated with SLC28A3-rs7853758 variant. Conclusion: In this cohort, 39.2% of patients carried the protective SLC28A3 variant. A small number of tested patients have the risk variants of UGT1A6 and RARG. None of the patients shared the two risk variants.

Vitamin D concentration and its association with parathyroid hormone in children and adolescents / Concentración de vitamina D y su relación con la hormona paratiroidea en niños y adolescentes

Abstract Background: Vitamin D (VD) deficiency has been inversely associated with parathyroid hormone (PTH) levels in the adult population but not in children and adolescents. This study aimed to report VD concentration and its correlation with PTH levels in a sample of healthy Mexican children. Methods: We conducted a cross-sectional study with 275 healthy Mexican subjects aged 2 to 17 years to estimate the status of 25-(OH)-D and its correlation with PTH levels. The 25-(OH)-D levels were estimated by liquid chromatography-tandem mass spectrometry and PTH by radioimmunoassay. Results: Subjects were categorized as young children (2 to 5 years), school children (6 to 10 years), and adolescents (11 to 17 years). The median concentration of 25-(OH)-D in young children was 27.4 ng/ml; in school children, 25.6 ng/ml; and adolescents, 24.7 ng/ml. VD levels < 20 ng/ml were found in only 10.5% of the participants. Only 3% of the young children showed VD deficiency, in contrast to 10% of school children and 21% of adolescents (p ≤ 0.05). PTH was found within normal ranges in 95.6% of the studied population. VD levels < 20 mg/dl were found in 25.8% of children with overweight or obesity (p = 0.009). Conclusions: VD levels < 20 ng/ml were observed in 10% of the studied group, but this percentage increased with age: 21% of the adolescents showed VD levels < 20 ng/ml. No correlation with PTH levels was found. The VD values reported in this study are lower than those previously reported in Mexican children.

Resumen Introducción: La deficiencia de vitamina D se ha asociado inversamente con la concentración de hormona paratiroidea (PTH) en los adultos, pero no en los niños y adolescentes. El objetivo de este estudio fue reportar la concentración de vitamina D y su correlación con la concentración de PTH en una muestra de niños mexicanos sanos. Métodos: Se llevó a cabo un estudio transversal con 275 mexicanos sanos de 2 a 17 años de edad en quienes se estimaron las concentraciones de 25-(OH)-D utilizando cromatografía líquida con espectrometría de masas y de PTH por radioinmunoensayo, y su correlación. Resultados: Los participantes se categorizaron como prescolares (2 a 5 años), escolares (6 a 10 años) y adolescentes (11 a 17 años). La mediana de la concentración de 25-(OH)-D en los prescolares fue de 27.4 ng/ml, en los escolares de 25.6 ng/ml y en los adolescentes de 24.7 ng/ml. Solo en el 10.5% de los participantes se encontraron valores de vitamina D < 20 ng/ml. En contraste con el 10% de los escolares y el 21% de los adolescentes, solo el 3% de los prescolares mostraron deficiencia de vitamina D (p ≤ 0.05). La PTH se encontró dentro de los límites normales en el 95.6% de la población estudiada. Se encontraron concentraciones de vitamina D < 20 mg/dl en el 25.8% de los niños con sobrepeso y obesidad (p = 0.009). Conclusiones: Solo en el 10% de los participantes se encontraron concentraciones de vitamina D < 20 ng/ml, pero este porcentaje aumento con la edad y se hallaron valores < 20 ng/ml en el 21% de los adolescentes. La PTH se encontró dentro de los valores normales. Las concentraciones de vitamina D en este estudio resultaron menores que las previamente reportadas en niños mexicanos.

Properties of protein unfolded states suggest broad selection for expanded conformational ensembles.

Much attention is being paid to conformational biases in the ensembles of intrinsically disordered proteins. However, it is currently unknown whether or how conformational biases within the disordered ensembles of foldable proteins affect function in vivo. Recently, we demonstrated that water can be a good solvent for unfolded polypeptide chains, even those with a hydrophobic and charged sequence composition typical of folded proteins. These results run counter to the generally accepted model that protein folding begins with hydrophobicity-driven chain collapse. Here we investigate what other features, beyond amino acid composition, govern chain collapse. We found that local clustering of hydrophobic and/or charged residues leads to significant collapse of the unfolded ensemble of pertactin, a secreted autotransporter virulence protein from Bordetella pertussis, as measured by small angle X-ray scattering (SAXS). Sequence patterns that lead to collapse also correlate with increased intermolecular polypeptide chain association and aggregation. Crucially, sequence patterns that support an expanded conformational ensemble enhance pertactin secretion to the bacterial cell surface. Similar sequence pattern features are enriched across the large and diverse family of autotransporter virulence proteins, suggesting sequence patterns that favor an expanded conformational ensemble are under selection for efficient autotransporter protein secretion, a necessary prerequisite for virulence. More broadly, we found that sequence patterns that lead to more expanded conformational ensembles are enriched across water-soluble proteins in general, suggesting protein sequences are under selection to regulate collapse and minimize protein aggregation, in addition to their roles in stabilizing folded protein structures.

Correlación de la masa muscular apendicular medida por absorciometría dual de rayos X y antropometría en población pediátrica y adolescente sana / Correlation of appendicular muscle mass measured with dual-energy X-ray absorptiometry and anthropometry in a healthy population of pediatric and adolescent subjects

Resumen Introducción: Durante el proceso de crecimiento y desarrollo, los niños y adolescentes presentan cambios en su composición corporal. La masa muscular apendicular está relacionada con la movilidad, deambulación y, consecuentemente, con las actividades de la vida diaria. El objetivo del estudio fue determinar la correlación de la masa magra apendicular (MMA) de los miembros superiores e inferiores mediante absorciometría dual de rayos X (DXA) como método de referencia, en comparación con el área muscular apendicular (AMA) obtenida mediante antropometría. Métodos: Estudio transversal en niños y adolescentes sanos de 5 a 20 años de edad, residentes de la Ciudad de México y Área Metropolitana. Se incluyeron y midieron 1,081 sujetos clínicamente sanos. Resultados: La MMA obtenida con DXA y el AMA obtenida por antropometría tienen un coeficiente de determinación (r2) de 0.90. Al categorizarlos por percentil de índice de masa corporal, este se mantiene, aunque es ligeramente menor en el grupo de sujetos con obesidad, donde el coeficiente fue de r2 = 0.84. Conclusiones: La determinación de la masa muscular apendicular en niños y adolescentes mexicanos mediante antropometría es válida y precisa, y presenta una alta correlación con métodos como la DXA. La antropometría podría implementarse como parte de la evaluación de la masa muscular apendicular en el primer nivel de atención.

Abstract Background: Children and adolescents present changes in their body composition during their growth and development process. The appendicular muscle mass (AMM) is related to mobility, ambulation and, consequently, with the activities of daily life. The objective of this study was to determine the correlation of the AMM of upper and lower limbs, obtained by dual X-ray absorptiometry (DXA), as a reference method compared to the appendicular muscular area (AMA) obtained by anthropometric measurements. Methods: Cross sectional study in healthy children and adolescents from 5 to 20 years of age, residents of Mexico City and the Metropolitan Area. A total sample of 1081 clinically healthy subjects were included. Results: The AMM obtained with DXA and the AMA obtained by anthropometry showed a coefficient of determination (r2) of 0.90. Categorizing by percentile of body mass index, the correlation is maintained, being slightly lower in the group of obese subjects, where the coefficient was r2 = 0.84. Conclusions: Measurement of AMM in Mexican children and adolescents with anthropometry is a valid and accurate technic with a high correlation with methods such as DXA. Anthropometry could be implemented as part of the assessment of AMM in the first level care.

Phase II randomized controlled trial of hypnosis versus progressive muscle relaxation for body image after breast or gynecologic cancer.

BACKGROUND: Sexual dysfunction, fueled by body image stress, is prevalent in women with a history of breast or gynecologic cancer. Preliminary data support that mind-body connections may improve sexual health outcomes through improving body image. OBJECTIVE: This randomized controlled trial compared hypnosis to progressive muscle relaxation (PMR). The primary outcome was body image at week 6 as measured by the Impact of Treatment Scale for women who have or have had breast or gynecologic cancer. INTERVENTIONS/METHODS: Consented participants were randomized 2:1 to hypnosis or PMR. Both arms consisted of three face-to-face sessions delivered by a trained therapist. Sessions were every 2 weeks for 6 weeks; participants practiced at home between sessions using an audio recording. RESULTS: Eighty-seven women were randomized, 59 to hypnosis and 28 to PMR. Both groups reported significant improvements on body image over time (within group effect size Cohen's d = 0.49-0.75) with no significant difference between groups (p = 0.15). Secondary outcomes were not significantly different between groups. The hypnosis group improved more in sexual satisfaction and sexual interest while the PMR group improved more in positive affect. CONCLUSIONS: Interventions facilitating mind-body connections such as hypnosis and PMR may help to improve body image. This study suggests that stress relieving strategies of hypnosis and PMR may contribute to providing a re-connection to one's body, improved positive affect, and overall better sexual health.

Reducing New-Onset Atrial Fibrillation After Coronary Artery Bypass Graft Surgery.

Postoperative atrial fibrillation is the most common dysrhythmia to occur after coronary artery bypass graft surgery. It develops in 10% to 40% of patients and can lead to complications such as hemodynamic instability, heart failure, and stroke. Risk factors include hypertension, diabetes, chronic kidney disease, and obesity. Patients who experience postoperative atrial fibrillation often have longer hospital stays, are at higher risk for readmission, and have increased mortality. Protocols designed to reduce the incidence of the condition can decrease hospital costs, improve patient outcomes, and increase overall quality of care. This quality improvement project took place in a tertiary care center located in southeastern Michigan and focused on the development and implementation of an evidence-based postoperative atrial fibrillation prophylaxis protocol using amiodarone. The outcomes of this project suggest that amiodarone prophylaxis can reduce the incidence of postoperative atrial fibrillation in patients with no previous history of atrial fibrillation undergoing coronary artery bypass graft surgery.

Commonly used FRET fluorophores promote collapse of an otherwise disordered protein.

The dimensions that unfolded proteins, including intrinsically disordered proteins (IDPs), adopt in the absence of denaturant remain controversial. We developed an analysis procedure for small-angle X-ray scattering (SAXS) profiles and used it to demonstrate that even relatively hydrophobic IDPs remain nearly as expanded in water as they are in high denaturant concentrations. In contrast, as demonstrated here, most fluorescence resonance energy transfer (FRET) measurements have indicated that relatively hydrophobic IDPs contract significantly in the absence of denaturant. We use two independent approaches to further explore this controversy. First, using SAXS we show that fluorophores employed in FRET can contribute to the observed discrepancy. Specifically, we find that addition of Alexa-488 to a normally expanded IDP causes contraction by an additional 15%, a value in reasonable accord with the contraction reported in FRET-based studies. Second, using our simulations and analysis procedure to accurately extract both the radius of gyration (Rg) and end-to-end distance (Ree) from SAXS profiles, we tested the recent suggestion that FRET and SAXS results can be reconciled if the Rg and Ree are "uncoupled" (i.e., no longer simply proportional), in contrast to the case for random walk homopolymers. We find, however, that even for unfolded proteins, these two measures of unfolded state dimensions remain proportional. Together, these results suggest that improved analysis procedures and a correction for significant, fluorophore-driven interactions are sufficient to reconcile prior SAXS and FRET studies, thus providing a unified picture of the nature of unfolded polypeptide chains in the absence of denaturant.