Regulators of rDNA array morphology in fission yeast.

Nucleolar morphology is a well-established indicator of ribosome biogenesis activity that has served as the foundation of many screens investigating ribosome production. Missing from this field of study is a broad-scale investigation of the regulation of ribosomal DNA morphology, despite the essential role of rRNA gene transcription in modulating ribosome output. We hypothesized that the morphology of rDNA arrays reflects ribosome biogenesis activity. We established GapR-GFP, a prokaryotic DNA-binding protein that recognizes transcriptionally-induced overtwisted DNA, as a live visual fluorescent marker for quantitative analysis of rDNA organization in Schizosaccharomyces pombe. We found that the morphology-which we refer to as spatial organization-of the rDNA arrays is dynamic throughout the cell cycle, under glucose starvation, RNA pol I inhibition, and TOR activation. Screening the haploid S. pombe Bioneer deletion collection for spatial organization phenotypes revealed large ribosomal protein (RPL) gene deletions that alter rDNA organization. Further work revealed RPL gene deletion mutants with altered rDNA organization also demonstrate resistance to the TOR inhibitor Torin1. A genetic analysis of signaling pathways essential for this resistance phenotype implicated many factors including a conserved MAPK, Pmk1, previously linked to extracellular stress responses. We propose RPL gene deletion triggers altered rDNA morphology due to compensatory changes in ribosome biogenesis via multiple signaling pathways, and we further suggest compensatory responses may contribute to human diseases such as ribosomopathies. Altogether, GapR-GFP is a powerful tool for live visual reporting on rDNA morphology under myriad conditions.

Predictors of Reoperation and Survival Experience (Minimum 1 Year) for Primary Versus Conversion Total Hip Arthroplasty in Young Patients.

BACKGROUND: Total hip arthroplasty (THA), including primary and conversion procedures, is commonly used for many types of joint disease in patients aged below 65 years, though few studies have evaluated THA outcomes in young patients (≤ 40 years old). This study examined a large cohort of patients who underwent THA at a young (≤ 40 years old) age to identify predictors of reoperation and compare survivorship between primary and conversion THAs. METHODS: A retrospective study was conducted on 497 patients who underwent 612 primary and conversion THAs at 40 years old or younger between 1990 and 2020. Medical records were reviewed to collect patient/surgical data. A multivariable logistic regression model identified independent predictors of reoperation, and Kaplan-Meier analysis with log-rank tests was used to compare survival curves by THA type. RESULTS: The median age at surgery (interquartile range) was 31 years (25 to 36). The median follow-up time was 6.6 years (range, 3.8 to 10.5). Conversion THAs had an increased rate of both revisions (12.3 versus 5.6%, P = 0.02) and nonrevision reoperations (8.9 versus 3.2%, P = 0.03) compared to primary THAs. A ceramic-on-ceramic articulation (odds ratio: 5.17; P = 0.03) and a higher estimated blood loss (odds ratio: 1.0007; P = 0.03) were independent predictors of reoperation for primary and conversion THA, respectively. Conversion THAs had a lower 15-year survival (77.8 versus 90.8%, P = 0.009) compared to primary THAs. CONCLUSIONS: Patients ≤ 40 years old who underwent primary and conversion THAs demonstrated an impressive 15-year survival comparable to that of older populations (74 to 93%), while conversion procedures had a higher reoperation rate. Although primary THA may be more ideal, there are promising outcomes for patients who need THA at a younger age than typically implemented, especially for those who are very young (≤ 30 years old).

Postoperative Vitamin D Surveillance and Supplementation in Revision Total Knee Arthroplasty Patients: A Retrospective Cohort Analysis.

This study was a retrospective cohort analysis of 20 patients who underwent 23 revision total knee arthroplasty procedures in a single geographic region of the United States from January 2015 to February 2023. We analyzed their 25-OH vitamin D levels preoperatively and postoperatively at 1 month, 3 months, 6 months, 1 year, and 2 years. We categorized their supplementation regimens by dose: none, low dose (1000 IU and below), medium dose (1001-5000 IU), and high dose (>5000 IU). We found that there was a high incidence of vitamin D deficiency in this patient population.

Predictors of reoperation and survival experience for primary total knee arthroplasty in young patients with degenerative and inflammatory arthritis.

INTRODUCTION: While total knee arthroplasty (TKA) is typically implemented in patients > 65 years old, young patients may need to undergo TKA for pain relief and functional improvement. Current data are limited by older cohorts and short-term survival rates. This study aimed to examine a large sample size of patients with degenerative and inflammatory conditions who underwent primary TKA at a young (≤ 40) age to identify predictors of reoperation, as well 15-year survivorship. MATERIALS AND METHODS: A retrospective study was performed on 77 patients (92 surgeries) who underwent primary TKA at ≤ 40 years old, between January 1990 and January 2020. Patient charts were reviewed and a multivariable logistic regression model identified independent predictors of reoperation. Kaplan-Meier analysis was employed to build survival curves and log-rank tests analyzed survival between groups. RESULTS: Of the 77 patients, the median age at the time of surgery was 35.7 years (IQR: 31.2-38.7) and median follow-up time was 6.88 years. Twenty-one (22.8%) primary TKAs underwent 24 reoperations, most commonly due to stiffness (n = 9, 32.1%) and infection (n = 13, 46.4%) more significantly in the OA group (p = 0.049). There were no independent predictors of reoperation in multivariable analysis, and 15-year revision-free survivorship after TKA did not differ by indication (77.3% for OA/PTOA vs. 96.7% for autoimmune, p = 0.09) or between ≤ 30 and 31-40 year age groups (94.7% vs. 83.6%, p = 0.55). CONCLUSIONS: In this cohort of patients ≤ 40 years old, revision-free survival was comparable to that reported in the literature for older TKA patients with osteoarthritis/autoimmune conditions (81-94% at 15-years). Though nearly a quarter of TKAs required reoperation and causes of secondary surgery differed between degenerative and inflammatory arthritis patients, there were no significant predictors of increased reoperation rate. Very young patients ≤ 30 years old did not have an increased risk of revision compared to those aged 31-40 years.

Association of Pharmacologic Treatment of Depression/Anxiety With Initial Patient-Reported Outcome Measures in Patients With Hip and Knee Osteoarthritis.

INTRODUCTION: Depression and anxiety are common comorbidities that may exacerbate osteoarthritis (OA)-related pain. We aim to evaluate the effect of pharmacologic treatment of depression/anxiety on hip and knee patient-reported outcome measures (PROMs). METHODS: A multi-institutional PROMs database was queried for patients with depression or anxiety and hip or knee OA who completed a PROMs questionnaire at an initial orthopaedic visit between January 2015 and March 2023. Data on demographics, comorbidities, and duration of pharmacologic treatment of depression/anxiety were obtained. Patients were stratified into three cohorts based on treatment duration. PROMs were compared across cohorts. RESULTS: Two thousand nine hundred sixty patients who completed PROMs at their initial orthopaedic visit had both OA and depression/anxiety. One hundred thirty-four (4.5%) received pharmacologic treatment of depression/anxiety for < 1 year, versus 196 (6.6%) for more than 1 year. In unadjusted analyses, patients with pharmacologic treatment had significantly lower Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical (39.8 [IQR 34.9, 44.9] vs 42.3 [37.4, 47.7], P < 0.001) and PROMIS-Mental (43.5 [36.3, 50.8] vs 48.3 [41.1, 53.3], P < 0.001) scores than those without treatment. After adjusting for demographics and comorbidities, only differences in PROMIS-Mental scores remained statistically significant, with pharmacologic treatment associated with lower scores (ß = -2.26, 95% CI, [-3.29, -1.24], P < 0.001). On secondary analysis including duration of pharmacologic treatment, < 1 year of treatment was associated with significantly lower PROMIS-Mental scores than those not treated (ß = -4.20, 95% CI [-5.77, -2.62], P < 0.001) while scores of patients with more than 1 year of treatment did not differ significantly from those without treatment. CONCLUSION: :Our results indicate that pharmacologic treatment of depression/anxiety is associated with improved psychological health but not with improved physical symptoms related to OA. We observed a nonsignificant trend that patients with depression/anxiety who warrant pharmacologic treatment tend to have worse physical symptoms than those who do not; however, unadjusted analyses suggest this is a complex relationship beyond the isolated effect of pharmacologic treatment.

Racial and Ethnic Minority Patients Have Increased Complication Risks When Undergoing Surgery While Not Meeting Clinical Guidelines.

BACKGROUND: Clinical guidelines for performing total joint arthroplasty (TJA) have not been uniformly adopted in practice because research has suggested that they may foster inequities in surgical access, potentially disadvantaging minority sociodemographic groups. The aim of this study was to assess whether undergoing TJA without meeting clinical guidelines affects complication risk and leads to disparities in postoperative outcomes. METHODS: This retrospective cohort study evaluated the records of 11,611 adult patients who underwent primary TJA from January 1, 2010, to December 31, 2020, at an academic hospital network. Based on self-reported race and ethnicity, 89.5% of patients were White, 3.5% were Black, 2.9% were Hispanic, 1.3% were Asian, and 2.8% were classified as other. Patients met institutional guidelines for undergoing TJA if they had a hemoglobin A1c of <8.0% and a body mass index of <40 kg/m 2 and were not currently smoking. A logistic regression model was utilized to identify factors associated with complications, and a mixed-effects model was utilized to identify factors associated with not meeting guidelines for undergoing TJA. RESULTS: During the study period, 11% (1,274) of the 11,611 adults who underwent primary TJA did not meet clinical guidelines. Compared with the group who met guidelines, the group who did not had higher proportions of Black patients (3.2% versus 6.0%; p < 0.001) and Hispanic patients (2.7% versus 4.6%; p < 0.001). An increased risk of not meeting guidelines at the time of surgery was demonstrated among Black patients (odds ratio [OR], 1.60 [95% confidence interval (CI), 1.22 to 2.10]; p = 0.001) and patients insured by Medicaid (OR, 1.75 [95% CI, 1.26 to 2.44]; p = 0.001) or Medicare (OR, 1.22 [95% CI, 1.06 to 1.41]; p = 0.007). Patients who did not meet guidelines had a higher risk of reoperation than those who met guidelines (7.7% [98] versus 5.9% [615]; p = 0.017), including a higher risk of infection-related reoperation (3.1% [40] versus 1.4% [147]; p < 0.001). CONCLUSIONS: We found that patients who underwent TJA despite not meeting institutional preoperative criteria had a higher risk of postoperative complications. These patients were more likely to be from racial and ethnic minority groups, to have a lower socioeconomic status, and to have Medicare or Medicaid insurance. These findings underscore the need for surgery-related shared decision-making that is informed by evidence-based guidelines in order to reduce complication burden. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Reverse Fragility Index: Comparing Revision Rates Between Direct Anterior and Other Approaches in Total Hip Arthroplasty. A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

Protein supersaturation powers innate immune signaling.

Innate immunity protects us in youth but turns against us as we age. The reason for this tradeoff is unclear. Seeking a thermodynamic basis, we focused on death fold domains (DFDs), whose ordered polymerization has been stoichiometrically linked to innate immune signal amplification. We hypothesized that soluble ensembles of DFDs function as phase change batteries that store energy via supersaturation and subsequently release it through nucleated polymerization. Using imaging and FRET-based cytometry to characterize the phase behaviors of all 109 human DFDs, we found that the hubs of innate immune signaling networks encode large nucleation barriers that are intrinsically insulated from cross-pathway activation. We showed via optogenetics that supersaturation drives signal amplification and that the inflammasome is constitutively supersaturated in vivo. Our findings reveal that the soluble "inactive" states of adaptor DFDs function as essential, yet impermanent, kinetic barriers to inflammatory cell death, suggesting a thermodynamic driving force for aging.

Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Assessment of Residual Pain and Dissatisfaction in Total Knee Arthroplasty: Methods Matter.

Background: Residual pain after total knee arthroplasty (TKA) refers to knee pain after 3 to 6 months postoperatively. The estimates of the proportion of patients who experience residual pain after TKA vary widely. We hypothesized that the variation may stem from the range of methods used to assess residual pain. We analyzed data from 2 prospective studies to assess the proportion of subjects with residual pain as defined by several commonly used metrics and to examine the association of residual pain defined by each metric with participant dissatisfaction. Methods: We combined participant data from 2 prospective studies of TKA outcomes from subjects recruited between 2011 and 2014. Residual pain was defined using a range of metrics based on the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score (0 to 100, in which 100 indicates worst), including the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). We also examined combinations of MCID and PASS cutoffs. Subjects self-reported dissatisfaction following TKA, and we defined dissatisfied as somewhat or very dissatisfied at 12 months. We calculated the proportion of participants with residual pain, as defined by each metric, who reported dissatisfaction. We examined the association of each metric with dissatisfaction by calculating the sensitivity, specificity, positive predictive value, and Youden index. Results: We analyzed data from 417 subjects with a mean age (and standard deviation) of 66.3 ± 8.3 years. Twenty-six participants (6.2%) were dissatisfied. The proportion of participants defined as having residual pain according to the various metrics ranged from 5.5% to >50%. The composite metric Improvement in WOMAC pain score ≥20 points or final WOMAC pain score ≤25 had the highest positive predictive value for identifying dissatisfied subjects (0.54 [95% confidence interval, 0.35 to 0.71]). No metric had a Youden index of ≥50%. Conclusions: Different metrics provided a wide range of estimates of residual pain following TKA. No estimate was both sensitive and specific for dissatisfaction in patients who underwent TKA, underscoring that measures of residual pain should be defined explicitly in reports of TKA outcomes. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal.

A long-standing goal of amyloid research has been to characterize the structural basis of the rate-determining nucleating event. However, the ephemeral nature of nucleation has made this goal unachievable with existing biochemistry, structural biology, and computational approaches. Here, we addressed that limitation for polyglutamine (polyQ), a polypeptide sequence that causes Huntington's and other amyloid-associated neurodegenerative diseases when its length exceeds a characteristic threshold. To identify essential features of the polyQ amyloid nucleus, we used a direct intracellular reporter of self-association to quantify frequencies of amyloid appearance as a function of concentration, conformational templates, and rational polyQ sequence permutations. We found that nucleation of pathologically expanded polyQ involves segments of three glutamine (Q) residues at every other position. We demonstrate using molecular simulations that this pattern encodes a four-stranded steric zipper with interdigitated Q side chains. Once formed, the zipper poisoned its own growth by engaging naive polypeptides on orthogonal faces, in a fashion characteristic of polymer crystals with intramolecular nuclei. We further show that self-poisoning can be exploited to block amyloid formation, by genetically oligomerizing polyQ prior to nucleation. By uncovering the physical nature of the rate-limiting event for polyQ aggregation in cells, our findings elucidate the molecular etiology of polyQ diseases.

Diseases that typically occur later in life, such as Alzheimer's, are often caused by specific proteins clumping together into structures known as amyloids. Once the process starts, amyloids will continue to form, leading to worse symptoms that cannot be cured. The best way to treat these diseases is therefore to stop amyloids from arising in the first place. Amyloids initially develop by proteins coming together to create an unstable structure referred to as the nucleus. The instability of the nucleus means it cannot be observed directly, making it hard to study this nucleation process. To overcome this, Kandola, Venkatesan et al. investigated the simplest protein known to form an amyloid ­ polyglutamine, which is made up of a chain of repeating building blocks known as amino acids. Polyglutamine forms only one type of amyloid which is associated with nine neurodegenerative diseases, including Huntington's disease. However, it only does this when its chain of amino acids exceeds a certain length, suggesting that a specific structure may be required for nucleation to begin. Kandola, Venkatesan et al. made alternative versions of the polyglutamine protein which each contained slightly different sequences of amino acids that will alter the way the protein folds. They then tested how well these different variants could form amyloids in yeast cells. This revealed that in order to join together into a nucleus, polyglutamine needs to be able to fold into a zipper shape made up of four interlocking strands. The length of the protein required to form this shape is also the same length that causes the amyloid associated with neurodegenerative diseases. Kandola, Venkatesan et al. also found that polyglutamine tends to bind to nuclei that have already formed in a way that hinders their growth. This 'self-poisoning' affect could potentially be exploited as a way to pre-emptively stop amyloids from initially arising. These findings have uncovered a potential therapeutic strategy for blocking amyloid formation that could eventually benefit people with or at risk of developing neurodegenerative diseases linked to polyglutamine. Additionally, this approach provides a blueprint for understanding how other proteins undergo amyloid nucleation, including those responsible for Alzheimer's, Parkinson's, and other diseases.

Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development.

While the accessibility of enhancers is dynamically regulated during development, promoters tend to be constitutively accessible and poised for activation by paused Pol II. By studying Lola-I, a Drosophila zinc finger transcription factor, we show here that the promoter state can also be subject to developmental regulation independently of gene activation. Lola-I is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers and reveal a mechanism for the de novo establishment of paused Pol II at promoters.

Age, Sex, and Education Level Predict Telehealth Engagement in Total Joint Arthroplasty Patients.

Background: Racial and other demographic predictors of total joint arthroplasty (TJA) telehealth engagement since the onset of the COVID-19 pandemic remain unclear. The purpose of the current study was to elucidate this relationship. Methods: A retrospective, cross-sectional study on 732 primary TJA patients was conducted within a single hospital system from March 2020-December 2021 (during the pandemic). Patients were excluded if their race or education level could not be determined. Patient demographics (age, sex, body mass index, language) and TJA information were obtained. The number of telehealth visits and telehealth engagement were assessed. Engagement (yes/no) and engagement frequency across all demographics and each measure of telehealth (telemedicine, patient-reported outcome measurements [PROMs], and electronic patient portal [EPP] messaging) were analyzed using multivariate logistic and linear regression, respectively. Results: Our results demonstrated that non-White race was not a significant predictor of binomial engagement or engagement frequency across all telehealth measures. Older age was a negative predictor of binomial engagement and engagement frequency with telemedicine and EPPs. Male sex was shown to be a negative predictor of binomial engagement with EPPs as well as PROM engagement frequency. Educational attainment of less than a college degree was a negative predictor of binomial engagement and engagement frequency with PROMs and EPPs. Conclusions: This study demonstrates that older age, male sex, and lower education level were negative predictors of various measures of telehealth engagement. Non-White race was not a significant predictor. This data informs providers on how to improve access to virtual orthopaedic care.

rRNA transcription is integral to phase separation and maintenance of nucleolar structure.

Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood. Here we show that homozygous null mutations in Pol I subunits required for rRNA transcription and ribosome biogenesis lead to preimplantation lethality. Moreover, we discovered that Polr1a-/-, Polr1b-/-, Polr1c-/- and Polr1d-/- mutants exhibit defects in the structure of their nucleoli, as evidenced by a decrease in number of nucleolar precursor bodies and a concomitant increase in nucleolar volume, which results in a single condensed nucleolus. Pharmacological inhibition of Pol I in preimplantation and midgestation embryos, as well as in hiPSCs, similarly results in a single condensed nucleolus or fragmented nucleoli. We find that when Pol I function and rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus increases, which disrupts its phase separation properties, leading to a single condensed nucleolus. However, if a cell progresses through mitosis, the absence of rRNA transcription prevents reassembly of the nucleolus and manifests as fragmented nucleoli. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity during development and in the pathogenesis of disease.

Sobrepeso y obesidad en Chile: Consideraciones para su abordaje en un contexto de inequidad social

Con 3 de cada 4 personas viviendo con sobrepeso u obesidad, la prevalencia de IMC elevado en Chile es de las más altas del continente, mostrando un patrón de distribución inequitativo mediado por determinantes estructurales que modelan el comportamiento en salud (seguridad social, nivel socioeconómico, educación, género, entre otros). Las características socioeconómicas del país, nación de ingresos altos con marcada inequidad, son poco comunes y representan un desafío adicional a la hora de diseñar intervenciones en salud. Una alta concentración de riqueza permite ser clasificado como país de ingresos altos aun cuando la mayor parte de la población pertenecería a una clase social vulnerable, cuyos ingresos se ven acompañados de recursos sociales y simbólicos que dificultan doblemente la adopción de un "estilo de vida" saludable. A pesar de las múltiples estrategias nutricionales implementadas, la prevalencia de sobrepeso y obesidad continúa en aumento. Se postula como gran responsable al insistente uso de modelos basados en elección y responsabilidad individual, que buscan modificar factores de riesgo conductuales (sedentarismo y alta ingesta calórica) sin neutralizar los determinantes estructurales que predisponen esa conducta. Favorablemente, la última Política Nacional de Nutrición reconoce la "determinación social de la alimentación", representando un cambio de paradigma que confiere cierto optimismo y cuya eficacia deberá ser evaluada en los próximos años.

With 3 out of 4 people living with overweight or obesity, the national prevalence of high BMI is among the highest on the continent, thus showing an inequitable distribution pattern mediated by structural determinants that shape health behavior (social security, socioeconomic status, education, gender, among others). The socioeconomic features of the country, a high-income nation with marked inequity, are unusual and represent an additional challenge when designing health interventions. A high concentration of wealth allows it to be classified as a high-income country even though most of the population would belong to a vulnerable social class, whose income is accompanied by social and symbolic resources that make it doubly challenging to adopt a healthy "lifestyle". Despite the multiple nutritional strategies implemented, the prevalence of overweight and obesity continues to increase. The insistent use of models based on individual choice and responsibility, which seek to modify behavioral risk factors (sedentary lifestyle and high caloric intake) without neutralizing the structural determinants predisposing this behavior, is postulated as highly responsible. Favorably, the latest National Nutrition Policy recognizes the "social determination of food", representing a paradigm shift that confers some optimism and whose effectiveness has to be evaluated in the coming years.

The Association of Sacro-Femoro-Pubic Angle and Postoperative Dislocation Following Total Hip Arthroplasty.

BACKGROUND: Spino-pelvic orientation may affect dislocation risk following total hip arthroplasty (THA). It can be measured on lateral lumbo-pelvic radiographs. The sacro-femoro-pubic (SFP) angle, measured on an antero-posterior (AP) pelvis radiograph, is a reliable proxy for pelvic tilt, a measurement of spino-pelvic orientation measured on a lateral lumbo-pelvic radiograph. The purpose of this study was to investigate the relationship between SFP angle and dislocation following THA. METHODS: An Institutional Review Board-approved retrospective case-control study was conducted at a single academic center. We matched 71 dislocators (cases) to 71 nondislocators (controls) following THA performed by 1 of 10 surgeons between September 2001 and December 2010. Two authors (readers) independently calculated SFP angle from single preoperative AP pelvis radiographs. Readers were blinded to cases and controls. Conditional logistic regressions were used to identify factors differentiating cases and controls. RESULTS: The data did not show a clinically relevant or statistically significant difference in SFP angles after adjusting for gender, American Society of Anesthesiologists classification, prosthetic head size, age at time of THA, measurement laterality, and surgeon. CONCLUSION: We did not find an association between preoperative SFP angle and dislocation following THA in our cohort. Based on our data, SFP angle as measured on a single AP pelvis radiograph should not be used to assess dislocation risk prior to THA.

Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube.

Signaling pathways regulate the patterns of Hox gene expression that underlie their functions in the specification of axial identity. Little is known about the properties of cis-regulatory elements and underlying transcriptional mechanisms that integrate graded signaling inputs to coordinately control Hox expression. Here, we optimized a single molecule fluorescent in situ hybridization (smFISH) technique with probes spanning introns to evaluate how three shared retinoic acid response element (RARE)-dependent enhancers in the Hoxb cluster regulate patterns of nascent transcription in vivo at the level of single cells in wild-type and mutant embryos. We predominately detect nascent transcription of only a single Hoxb gene in each cell, with no evidence for simultaneous co-transcriptional coupling of all or specific subsets of genes. Single and/or compound RARE mutations indicate that each enhancer differentially impacts global and local patterns of nascent transcription, suggesting that selectivity and competitive interactions between these enhancers is important to robustly maintain the proper levels and patterns of nascent Hoxb transcription. This implies that rapid and dynamic regulatory interactions potentiate transcription of genes through combined inputs from these enhancers in coordinating the retinoic acid response.

Are There More Radiolucent Lines in Patients Who Underwent Total Knee Arthroplasty With or Without a Tourniquet During Cementation at 5 to 8 Years After Surgery?

BACKGROUND: This study investigated the presence and progression of radiolucent lines (RLLs) after cemented total knee arthroplasty (TKA) with or without tourniquet use. METHODS: There were 369 consecutive primary cemented TKAs with 5 to 8 years of follow-up. A tourniquet was used during component cementation in patients who underwent surgery from January 3, 2006, to March 31, 2010. No tourniquet was used from August 14, 2009, to October 14, 2014. There were 192 patients in the tourniquet group (TQ) and 177 patients in the no tourniquet group (NQ). Patient demographics, reoperations, and complications were recorded. RLLs were identified on anteroposterior, lateral, and skyline x-rays at 1, 2, and 5 to 8 years postoperatively using the modern knee society radiographic evaluation system. Demographics, reoperations, complications, and RLLs were compared. Age, sex, and body mass index were similar between groups. Mean tourniquet time in TQ was 11 minutes (range, 8 to 25). RESULTS: The presence of RLLs differed between groups, with 65% of TQ knees having RLLs under any part of the prostheses versus 46% of NQ knees (P < .001). The progression of RLL >2 mm occurred in 26.0% of knees in TQ and 16.7% of knees in NQ (P = .028). There were 13 TKAs that underwent subsequent revision surgery. There was no statistically or clinically significant difference in revision rate between groups (7 revisions in TQ, 6 in NQ, P = .66). CONCLUSION: Less RLLs were identified in NQ versus TQ. There were no statistically or clinically significant differences in revision rates between the NQ and TQ groups at 5 to 8 years.

Patient-Specific Safe Zones for Acetabular Component Positioning in Total Hip Arthroplasty: Mathematically Accounting for Spinopelvic Biomechanics.

BACKGROUND: Despite a growing understanding of spinopelvic biomechanics in total hip arthroplasty (THA), there is no validated approach for executing patient-specific acetabular component positioning. The purpose of this study was to (1) validate quantitative, patient-specific acetabular "safe zone" component positioning from spinopelvic parameters and (2) characterize differences between quantitative patient-specific acetabular targets and qualitative hip-spine classification targets. METHODS: From 2,457 consecutive primary THA patients, 22 (0.88%) underwent revision for instability. Spinopelvic parameters were measured prior to index THA. Acetabular position was measured following index and revision arthroplasty. Using a mathematical proof, we developed an open-source tool translating a surgeon-selected, preoperative standing acetabular target to a patient-specific safe zone intraoperative acetabular target. Difference between the patient-specific safe zone and the actual component position was compared before and after revision. Hip-spine classification targets were compared to patient-specific safe zone targets. RESULTS: Of the 22 who underwent revision, none dislocated at follow-up (4.6 [range, 1 to 6.9]). Patient-specific safe zone targets differed from prerevision acetabular component position by 9.1 ± 4.2° inclination/13.3 ± 6.7° version; after revision, the mean difference was 3.2 ± 3.0° inclination/5.3 ± 2.7° version. Differences between patient-specific safe zones and the median and extremes of recommended hip-spine classification targets were 2.2 ± 1.9° inclination/5.6 ± 3.7° version and 3.0 ± 2.3° inclination/7.9 ± 3.5° version, respectively. CONCLUSION: A mathematically derived, patient-specific approach accommodating spinopelvic biomechanics for acetabular component positioning was validated by approximating revised, now-stable hips within 5° version and 3° inclination. These patient-specific safe zones augment the hip-spine classification with prescriptive quantitative targets for nuanced preoperative planning.