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.

Incidence of hip fractures in Mexico 2006-2019: increasing numbers but decreasing rates.

This study, characterizing the incidence of hip fractures in Mexico, showed not only that the crude number of fractures has increased, but also there has been a decrease in fracture rates. Nonetheless, as the population ages in the coming decades, the current declines rate of could be expected to reverse. PURPOSE: This study is to examine the incidence, rates, and time trends of hip fractures from 2006 to 2019 in Mexico. Additionally, an analysis of the follow-up of the birth cohorts was carried out. METHODS: Hip fractures registered during the period of the study were obtained through the Mexican Social Security Institute (IMSS) national discharge records. The incidence per 100,000 individuals was calculated from the IMSS population at risk. A time trend analysis was conducted using linear regression, and the identification of breakpoints in linear trends. RESULTS: There was an increase of hip fractures for both sexes ≥ 60 years (43% for women and 41%, for men). However, the rates diminished from 167.8/100,000 in 2006 to 138.5 /100,000 in the population 60 and over (1.9% and 0.9% per year in women and men respectively). When the information was analyzed by age groups, hip fracture rates were similar in both sexes but higher in women. The most significant contribution to the total number of fractures is due to the groups ≥ 70 years; people born before 1937 are accounting for the burden of fractures over the total data. In contrast, the younger generations appear to have lower rates. CONCLUSION: Rates of hip fracture have steadily declined in Mexico since 2006; however, with the population aging in the coming decades, current rates declines could be expected to reverse.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP.

DegP is an oligomeric protein with dual protease and chaperone activity that regulates protein homeostasis and virulence factor trafficking in the periplasm of gram-negative bacteria. A number of oligomeric architectures adopted by DegP are thought to facilitate its function. For example, DegP can form a "resting" hexamer when not engaged to substrates, mitigating undesired proteolysis of cellular proteins. When bound to substrate proteins or lipid membranes, DegP has been shown to populate a variety of cage- or bowl-like oligomeric states that have increased proteolytic activity. Though a number of DegP's substrate-engaged structures have been robustly characterized, detailed mechanistic information underpinning its remarkable oligomeric plasticity and the corresponding interplay between these dynamics and biological function has remained elusive. Here, we have used a combination of hydrodynamics and NMR spectroscopy methodologies in combination with cryogenic electron microscopy to shed light on the apo-DegP self-assembly mechanism. We find that, in the absence of bound substrates, DegP populates an ensemble of oligomeric states, mediated by self-assembly of trimers, that are distinct from those observed in the presence of substrate. The oligomeric distribution is sensitive to solution ionic strength and temperature and is shifted toward larger oligomeric assemblies under physiological conditions. Substrate proteins may guide DegP toward canonical cage-like structures by binding to these preorganized oligomers, leading to changes in conformation. The properties of DegP self-assembly identified here suggest that apo-DegP can rapidly shift its oligomeric distribution in order to respond to a variety of biological insults.

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.

An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS.

INTRODUCTION: EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. METHODS: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. RESULTS: TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. CONCLUSIONS: We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states.

Calcium and vitamin D for increasing bone mineral density in premenopausal women.

BACKGROUND: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. OBJECTIVES: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. SELECTION CRITERIA: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. MAIN RESULTS: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm2, 95% confidence interval (CI) -0.11 to 0.03; I2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm2, 95% CI -0.06 to 0.06; I2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I2 = 72%; 2 studies, 541 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

Albuminuria, Disease Duration, and Glycated Hemoglobin Are Related With Bone Mineral Density in Type 1 Diabetes: A Cross-sectional Study.

OBJECTIVE: Studies have found a significant decrease in bone mineral density (BMD) in individuals with type 1 diabetes (T1D) compared to healthy controls. Factors associated with this phenomenon have yet to be defined; therefore, this study aimed to explore the association of glycated hemoglobin (HbA1c), disease duration, albuminuria, and glomerular filtration rate with BMD in adults with T1D. METHODS: A cross-sectional study was carried out in tertiary care center. BMD analysis was performed by dual x-ray absorptiometry. Linear models were constructed considering variables associated with BMD. Approval from the ethics committees and informed consent were obtained. RESULTS: We included 128 participants, of whom 59% were women, and 16% had menopause. The median age was 33 (26-42) years. The average age of diabetes diagnosis was 15.3 ± 6.3 years, and the median disease duration was 19.5 (12-27) years. In the adjusted analysis, higher albuminuria (P < .01) and disease duration (P < .05) were associated with a lower BMD in the femoral neck and total hip, independently of age, sex, and body mass index (BMI). Higher HbA1c (P < .01) was associated with a lower spine BMD after adjustment for age, sex, and BMI. CONCLUSION: Studied factors specific to T1D, including albuminuria, disease duration, and HbA1c have an association with BMD regardless of BMI, age, and sex.

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.

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.

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.

Chronic arthritides and bone structure: focus on rheumatoid arthritis-an update.

Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.

Synonymous codon substitutions perturb cotranslational protein folding in vivo and impair cell fitness.

In the cell, proteins are synthesized from N to C terminus and begin to fold during translation. Cotranslational folding mechanisms are therefore linked to elongation rate, which varies as a function of synonymous codon usage. However, synonymous codon substitutions can affect many distinct cellular processes, which has complicated attempts to deconvolve the extent to which synonymous codon usage can promote or frustrate proper protein folding in vivo. Although previous studies have shown that some synonymous changes can lead to different final structures, other substitutions will likely be more subtle, perturbing predominantly the protein folding pathway without radically altering the final structure. Here we show that synonymous codon substitutions encoding a single essential enzyme lead to dramatically slower cell growth. These mutations do not prevent active enzyme formation; instead, they predominantly alter the protein folding mechanism, leading to enhanced degradation in vivo. These results support a model in which synonymous codon substitutions can impair cell fitness by significantly perturbing cotranslational protein folding mechanisms, despite the chaperoning provided by the cellular protein homeostasis network.

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.

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.

Neighborhood socioeconomic disadvantage measures in rehabilitation clinical trials: Lessons learned in recruitment.

PURPOSE: The Area Deprivation Index (ADI) measures the relative disadvantage of an individual or social network using US Census indicators. Although a strong re-hospitalization predictor, ADI has not been routinely incorporated into rehabilitation research. The purposes of this paper are to examine the use of ADI related to study recruitment, association with carepartner psychosocial factors, and recruitment strategies to increase participant diversity. METHODS: Descriptive analysis of baseline data from a pilot stroke carepartner-integrated therapy trial. Participants were 32 carepartners (N = 32; 62.5 % female; mean age 57.8 ± 13.0 years) and stroke survivors (mean age (60.6 ± 14.2) residing in an urban setting. Measures included ADI, Bakas Caregiver Outcome Scale, Caregiver Strain Index, and Family Assessment Device. RESULTS: Most carepartners were Non-Hispanic White participants (61.3 %), part or fully employed (43 %), with >$50,000 (67.7 %) income, and all had some college education. Most stroke survivors were Non-Hispanic White participants (56.3 %) with some college (81.3 %). Median ADI state deciles were 3.0 (interquartile range 1.5-5, range 1-9), and mean national percentiles were 41.7 ± 23.5 with only 6.3 % of participants from the most disadvantaged neighborhoods. For the more disadvantaged half of the state deciles, the majority were Black or Asian participants. No ADI and carepartner factors were statistically related. CONCLUSIONS: The use of ADI data highlighted a recruitment gap in this stroke study, lacking the inclusivity of participants from disadvantaged neighborhoods and with lower education. Using social determinants of health indicators to identify underrepresented neighborhoods may inform recruitment methods to target marginalized populations and broaden the generalizability of clinical trials.

Analysis of musculoskeletal disorders-associated disability in Mexico from 1990 to 2021.

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.

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.

Multi-layer sequential network analysis improves protein 3D structural classification.

Protein structural classification (PSC) is a supervised problem of assigning proteins into pre-defined structural (e.g., CATH or SCOPe) classes based on the proteins' sequence or 3D structural features. We recently proposed PSC approaches that model protein 3D structures as protein structure networks (PSNs) and analyze PSN-based protein features, which performed better than or comparable to state-of-the-art sequence or other 3D structure-based PSC approaches. However, existing PSN-based PSC approaches model the whole 3D structure of a protein as a static (i.e., single-layer) PSN. Because folding of a protein is a dynamic process, where some parts (i.e., sub-structures) of a protein fold before others, modeling the 3D structure of a protein as a PSN that captures the sub-structures might further help improve the existing PSC performance. Here, we propose to model 3D structures of proteins as multi-layer sequential PSNs that approximate 3D sub-structures of proteins, with the hypothesis that this will improve upon the current state-of-the-art PSC approaches that are based on single-layer PSNs (and thus upon the existing state-of-the-art sequence and other 3D structural approaches). Indeed, we confirm this on 72 datasets spanning ~44 000 CATH and SCOPe protein domains.

Short- and long-term prognostic factors associated with functional recovery in elderly patients with hip fracture: A systematic review.

This systematic review aimed to identify short- and long-term associated factors to functional recovery of elderly hip fracture patients after discharge. We identified 43 studies reporting 74 associated factors to functional recovery; most of them were biological, sociodemographic, or inherent factors to patients' baseline characteristics, including their pre-facture functional capacity. PURPOSE: This systematic review aimed to identify short- and long-term associated factors to functional recovery of elderly hip fracture patients after hospital discharge. We assessed the use of the hip fracture core-set and key-performance indicators for secondary fracture reduction. METHODS: A search was performed in seven electronic databases. Observational studies reporting predictors after usual care of elderly patients with hip fracture diagnoses receiving surgical or conservative treatment were included. Primary outcomes considered were part of the domains corresponding to functional capacity. RESULTS: Of 3873 references identified, and after the screening and selection process, 43 studies were included. Sixty-one functional measures were identified for ten functional outcomes, including BADLs, IADLs, ambulation, and mobility. Biological characteristics such as age, sex, comorbidities, cognitive status, nutritional state, and biochemical parameters are significantly associated. Determinants such as contact and size of social network and those related to institutional care quality are relevant for functional recovery at six and 12 months. Age, pre-fracture function, cognitive status, and complications continue to be associated five years after discharge. We found 74 associated factors to functional recovery of elderly hip fracture patients. Ten of the studies reported rehabilitation programs as suggested in KPI 9; none used the complete hip fracture core-set. CONCLUSION: Most of the associated factors for functional recovery of elderly hip fracture were biological, sociodemographic, or inherent factors to patients' baseline characteristics, including their pre-facture functional capacity. For the core-set and KPI's, we found an insufficient use and report. This study reports 61 different instruments to measure functional capacity. REGISTRATION NUMBER: PROSPERO (CRD42020149563).