Osteoporosis and Fragility Fractures in Mexico: A Call to Action.

Osteoporosis (OP) is a chronic disease that affects older adults' quality of life, with fragility fractures (FF) being its most significant consequence due to their impact on healthcare systems in terms of morbidity, and economic and caregiving burden. FF are defined as fractures resulting from low-energy trauma, defined as falls from a standing height or less, and are usually considered osteoporotic (1). World demographic projections warn of a significant increase in adults aged 65 and older by 2050. These demographic changes mean that OP and FF will soon become an even greater challenge for healthcare systems, where prevention programs should be a priority. In Mexico, FF is also a public health challenge, with an initial reported incidence of nearly 2,000 cases per 100,000 population, and a projected seven-fold increase by 2050. Given this scenario, there is an urgent need for policy- and decision-makers to change their approach and formulate health policies that guarantee that people aged 65 and older are screened for fractures and have access to appropriate care. These policies should be part of a strategy to minimize FF and ensure active and healthy aging according to the WHO's Decade of Healthy Ageing. In this context, a group of Mexican experts representing different health organizations interested in the burden of OP and FF met to discuss possible strategies to reduce their burden for the next decade and summarize them in this Call to Action to promote public policies that prioritize an evidence-based approach to the prevention and treatment of OP and FF.

Synonymous codon substitutions modulate transcription and translation of a divergent upstream gene by modulating antisense RNA production.

Synonymous codons were originally viewed as interchangeable, with no phenotypic consequences. However, substantial evidence has now demonstrated that synonymous substitutions can perturb a variety of gene expression and protein homeostasis mechanisms, including translational efficiency, translational fidelity, and cotranslational folding of the encoded protein. To date, most studies of synonymous codon-derived perturbations have focused on effects within a single gene. Here, we show that synonymous codon substitutions made far within the coding sequence of Escherichia coli plasmid-encoded chloramphenicol acetyltransferase (cat) can significantly increase expression of the divergent upstream tetracycline resistance gene, tetR. In four out of nine synonymously recoded cat sequences tested, expression of the upstream tetR gene was significantly elevated due to transcription of a long antisense RNA (asRNA) originating from a transcription start site within cat. Surprisingly, transcription of this asRNA readily bypassed the native tet transcriptional repression mechanism. Even more surprisingly, accumulation of the TetR protein correlated with the level of asRNA, rather than total tetR RNA. These effects of synonymous codon substitutions on transcription and translation of a neighboring gene suggest that synonymous codon usage in bacteria may be under selection to both preserve the amino acid sequence of the encoded gene and avoid DNA sequence elements that can significantly perturb expression of neighboring genes. Avoiding such sequences may be especially important in plasmids and prokaryotic genomes, where genes and regulatory elements are often densely packed. Similar considerations may apply to the design of genetic circuits for synthetic biology applications.

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).

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.

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.

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.

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.

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.

The Effects of Codon Usage on Protein Structure and Folding.

The rate of protein synthesis is slower than many folding reactions and varies depending on the synonymous codons encoding the protein sequence. Synonymous codon substitutions thus have the potential to regulate cotranslational protein folding mechanisms, and a growing number of proteins have been identified with folding mechanisms sensitive to codon usage. Typically, these proteins have complex folding pathways and kinetically stable native structures. Kinetically stable proteins may fold only once over their lifetime, and thus, codon-mediated regulation of the pioneer round of protein folding can have a lasting impact. Supporting an important role for codon usage in folding, conserved patterns of codon usage appear in homologous gene families, hinting at selection. Despite these exciting developments, there remains few experimental methods capable of quantifying translation elongation rates and cotranslational folding mechanisms in the cell, which challenges the development of a predictive understanding of how biology uses codons to regulate protein folding.

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.

Evaluation of a carepartner-integrated telehealth gait rehabilitation program for persons with stroke: study protocol for a feasibility study.

BACKGROUND: Despite family carepartners of individuals post-stroke experiencing high levels of strain and reduced quality of life, stroke rehabilitation interventions rarely address carepartner well-being or offer training to support their engagement in therapeutic activities. Our group has developed creative intervention approaches to support families during stroke recovery, thereby improving physical and psychosocial outcomes for both carepartners and stroke survivors. The purpose of this study is to test the feasibility of an adapted, home-based intervention (Carepartner Collaborative Integrative Therapy for Gait-CARE-CITE-Gait) designed to facilitate positive carepartner involvement during home-based training targeting gait and mobility. METHODS: This two-phased design will determine the feasibility of CARE-CITE-Gait, a novel intervention that leverages principles from our previous carepartner-focused upper extremity intervention. During the 4-week CARE-CITE-Gait intervention, carepartners review online video-based modules designed to illustrate strategies for an autonomy-supportive environment during functional mobility task practice, and the study team completes two 2-h home visits for dyad collaborative goal setting. In phase I, content validity, usability, and acceptability of the CARE-CITE-Gait modules will be evaluated by stroke rehabilitation content experts and carepartners. In phase II, feasibility (based on measures of recruitment, retention, intervention adherence, and safety) will be measured. Preliminary effects of the CARE-CITE-Gait will be gathered using a single-group, quasi-experimental design with repeated measures (two baseline visits 1 week apart, posttest, and 1-month follow-up) with 15 carepartner and stroke survivor dyads. Outcome data collectors will be blinded. Outcomes include psychosocial variables (family conflict surrounding stroke recovery, strain, autonomy support, and quality of life) collected from carepartners and measures of functional mobility, gait speed, stepping activity, and health-related quality of life collected from stroke survivors. DISCUSSION: The findings of the feasibility testing and preliminary data on the effects of CARE-CITE-Gait will provide justification and information to guide a future definitive randomized clinical trial. The knowledge gained from this study will enhance our understanding of and aid the development of rehabilitation approaches that address both carepartner and stroke survivor needs during the stroke recovery process. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05257928. Registered 25 February 2022. TRIAL STATUS: This trial was registered on ClinicalTrials.gov (NCT05257928) on March 25, 2022. Recruitment of participants was initiated on May 18, 2022.

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.

Publishing Quality Improvement Projects: Know the Guidelines Before Starting Your Project.

Health care clinicians, educators, and students who plan and implement quality improvement (QI) projects must know reporting guidelines for successful project planning and publication. We aimed to identify QI guidelines, which authors can locate, and highlight how best to use them for manuscript preparation. We also address guidelines for educational QI projects. Because of the increasing number of Doctor of Nursing Practice projects generated, these students and their mentors must be familiar with commonly used guidelines for reporting QI projects to facilitate peer review, demonstrate quality and rigor of work, reduce revisions, and potentially accelerate a paper's acceptance for publication.

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.

Evaluating the Effectiveness of a Virtual Mock Interview for Health Professions Students.

BACKGROUND: Virtual mock interviews were offered to students to improve job interviewing skills. This educational quality improvement project aimed to use virtual mock interviews to increase student preparedness and confidence, and reduce anxiety related to professional interviews. METHOD: Health professions students (n = 19) participated in the mock interviews conducted and recorded through a web-based meeting. Students received the recorded interview to watch before follow-up. Students completed pre- and postquestionnaires that addressed students' preparedness, confidence, and anxiety related to interviewing. RESULTS: Participants' confidence and preparedness improved significantly in their virtual interviews (p < .001), and their anxiety decreased significantly after the virtual interviews (p < .001). After watching the interviews, students' reported eye contact needed improvement and answers included too many "uhms." CONCLUSION: Students benefited from the virtual mock interviews. Mock virtual job interviews may have a positive effect on successful job acquisition in health professions. [J Nurs Educ. 2023;62(8):479-482.].

Simultaneous Recording of Objective Sleep in Mothers and School-aged Children with Developmental Disabilities: A Pilot Study of Actigraphy and Videosomnography.

Mothers of school-aged children ages 3 to 17 years with developmental disabilities (DDs) commonly report sleep problems in their children associated with impaired maternal sleep. However, existing research relies heavily on mothers' self-reported sleep. This study aimed to determine the feasibility of objectively measuring child and mother sleep-wake patterns using actigraphy and videosomnography. This was an observational pilot study. Mothers wore actigraphy watches and video-recorded their child's sleep for 7 nights. Mothers also completed a 7-day sleep diary and questionnaires on sleep quality, depressive symptoms, stress, and child sleep problems. Ten mothers (32-49 years) and ten children with DDs (8-12 years) completed this study. Half of the children were boys with autism spectrum disorders. We successfully recruited 77% of eligible mothers for the study during the pandemic. Eight mothers successfully wore the actigraphy, and nine successfully video-recorded their child's sleep. Mothers rated their participation positively and considered the data collection protocol acceptable. While mothers' sleep patterns from actigraphy were mostly within recommendations, self-reported sleep quality was poor. Child's sleep estimates from videosomnography showed children slept substantially less than recommended sleep hours. Mothers also reported a high frequency of child sleep problems. Consistent with this pattern, mothers also endorsed elevated stress and depression. The use of actigraphy and videosomnography is feasible. Objective sleep measurement for mothers' and children's sleep is needed with self-report to measure multidimensional aspects of sleep and discrepancies between objective and self-report sleep measures. Future studies can use multi-methods sleep measures and work toward interventions that can improve family sleep and reduce mothers' stress and depression.

The Real Secret to Getting Published: Responding to Reviewers.

Authors submitting a paper often receive an opportunity to revise and resubmit the paper. Authors may find addressing reviewers' comments challenging. We posit authors should welcome expert suggestions for revisions that strengthen the paper and develop a persuasive response if they disagree with the reviewer. A thoughtful, detailed response allows authors to dialogue with reviewers. Our paper uses exemplars of responses to reviewers to illustrate the effectiveness of clear and compelling author responses. Addressing reviewers' comments ultimately results in a better paper-more likely to be accepted. Developing skills in resubmitting research and clinical scholarship reports is essential to the dissemination process.

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.