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Summary: Difference-in-differences (DID) is a key tool for causal impact evaluation but faces challenges when applied to sensitive data restricted by privacy regulations. Obtaining consent can shrink sample sizes and reduce statistical power, limiting the analysis’s effectiveness. Federated learning addresses these issues by sharing aggregated statistics rather than individual data, though advanced federated DID software is limited. We developed a federated version of the Callaway and Sant’Anna difference-in-differences (CSDID), integrated into the DataSHIELD platform, adhering to stringent privacy protocols. Our approach reproduces key estimates and standard errors while preserving confidentiality. Using simulated and real-world data from a malaria intervention in Mozambique, we demonstrate that federated estimates increase sample sizes, reduce estimation uncertainty, and enable analyses when data owners cannot share treated or untreated group data. Our work contributes to facilitating the evaluation of policy interventions or treatments across centers and borders.

Abstract Background Shoulder pain is a leading cause of disability. Occupations requiring high upper extremity demands may put workers at greater risk of shoulder injury and resulting pain. We examined associations of occupation with shoulder pain and upper extremity disability in the Johnston County Osteoarthritis Project. Methods Work industry and occupational tasks for the longest job held were collected from participants. At follow-up ranging from 4–10 years later, participants were asked about shoulder symptoms (pain, aching, or stiffness occurring most days of 1 month in the last year) and given a 9-item, modified Disabilities Arm Shoulder and Hand (DASH) questionnaire to categorize disability from 0–4 (none-worst). Logistic regression and cumulative logit regression models were used to estimate associations with prevalent shoulder symptoms and with worse disability category, respectively. Models were adjusted for cohort, age, sex, race, education and time to follow-up. Sex- and race-stratified associations were evaluated. Results Among 1560 included participants, mean age was 62 years (standard deviation ± 9 years); 32% were men, and 31% were Black. Compared to the managerial/professional industry, higher odds of both shoulder symptoms and worse upper extremity disability were seen for most industrial groups with physically demanding jobs, particularly the service industry. Work that often or always required lifting/moving > 10 lbs. was associated with higher odds of shoulder symptoms. Work that sometimes or always required heavy work while standing was associated with higher odds of shoulder symptoms, and this association was stronger among men and White workers. Conclusion Physically demanding occupations were associated with increased occurrence of shoulder pain and disability. Mitigating specific physical work demands may reduce shoulder-related disability.

HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive non-remitting and incapacitating disease more frequently seen in women and with a patchy worldwide distribution. HAM/TSP develops in a small percentage of HTLV-1-infected individuals during their lifetime and etiologic factors for disease progression are still unclear. This study aims to describe the first case series of the progression of HAM/TSP in relation to pregnancy. Between January and March of 2012, we reviewed medical charts of women with HAM/TSP currently enrolled in the HTLV-1 cohort at the institute of tropical medicine of Cayetano Heredia University. Inclusion criteria included having a diagnosis of HAM/TSP according to the WHO guidelines and self-reported initial symptoms of HAM/TSP during pregnancy or within six months of delivery. Fifteen women reported having had symptoms compatible with HAM/TSP within four months of delivery. Among them, ten women had no symptoms before pregnancy and reported gait impairment after delivery. Five women with mild gait impairment before pregnancy noticed a worsening of their symptoms after delivery. Symptoms worsened after successive pregnancies. Recent studies have shown that HTLV-1 infection induces a strong T cell-mediated response and that the quality of this response plays a role in HAM/TSP pathogenesis. The relative immunosuppression during pregnancy, including blunting of the T-cell response, might allowed in certain women enhanced replication of HTLV-1 and disease progression in the postpartum. This is the first study looking specifically at HAM/TSP and pregnancy and the number of cases is remarkable. Further prospective studies of HTLV-1-infected women assessing immune markers during pregnancy are warranted. Breastfeeding was the main route of transmission. Strategies to prevent vertical transmission need to be evaluated in HTLV-1 endemic countries of Latin America.

Abstract Introduction Immune checkpoint inhibitors (ICIs) enhance the immune system’s ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes. Methods We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan–Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test. Results We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0–56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19–3.76) or new onset irAE (OR 3.21, 95% CI 0.83–13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52). Conclusion The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.

En el marco de un proyecto de extensión de mapeo participativo con comunidades comechingonas- sanavironas en el noroeste de la provincia de Córdoba, nos topamos con experiencias que nos desafiaron a pensar nuestro quehacer, los métodos y técnicas utilizadas para los relevamientos territoriales así como los afectos y efectos involucrados en la confección de una cartografía social. En este trabajo me interesa reparar en la experiencia sensible de recorrer el camino de Yastay, en las dificultades de un camino de monte que se cerraba con su vegetación tupida pero se abría a nosotros. Recorrer el camino nos permitió conocer sitios rituales y afectivos donde habitan espíritus y otros no humanos, así como repensar las relaciones y afectaciones mutuas al recorrer y relevar el territorio, que ponen de manifiesto diversas formas de territorear.

Objective To assess the feasibility and changes in outcomes of a 12‐week high‐intensity interval training (HIIT) program in individuals with symptomatic knee osteoarthritis (OA). Methods The single‐arm trial included 29 participants (mean ± SD age 63 ± 7 years; 66% women; 66% obese). Measures of participant flow, adherence, and tolerability were collected. Pain, function, and balance were assessed at baseline, 6 weeks, and 12 weeks using the Western Ontario and McMaster Universities Osteoarthritis Index, 20‐m fast‐paced walk test, 30‐second chair‐stand test, stair‐climb test, timed up and go test, and single leg stance. Cardiorespiratory fitness, strength, and body composition were evaluated using peak oxygen consumption (VO2peak), isometric knee extensor/flexor strength, and dual‐energy x‐ray absorptiometry, respectively. HIIT was completed two times/week (cycling or treadmill) and consisted of 10 repetitions of 1‐minute bouts at 90% VO2peak, with 1‐minute rest periods. Separate multivariable‐adjusted linear mixed models were fit for each outcome with fixed effects of time, age, sex, body mass index, and random effects of baseline values to estimate mean changes and 95% confidence intervals (CIs) between baseline and 12‐week assessments. Results Recruitment aligned with the anticipated enrollment rate, adherence was 70%, and no adverse events were reported. At 12 weeks, improvements were observed for most outcomes, with notable mean changes for the 20‐m fast‐paced walk (−1.13 [95% CI −1.61 to −0.64] seconds), 30‐second chair‐stand (2.6 [1.8‐3.4] stands), and VO2peak (0.14 [0.03‐0.24] liters/minute). Conclusion In this 12‐week pilot study, HIIT improved multiple aspects of health in individuals with knee OA; larger studies are needed.

Objective SLE primarily affects women of childbearing age, who have an increased risk of pregnancy complications, especially in the setting of active disease. Contraception counselling is particularly important given the teratogenicity of some medications used for SLE treatment. Our study describes the frequency of contraception counselling provided by multiple subspecialties to women with SLE and investigates associations between teratogenic medication use and receiving contraception counselling.Methods This was a cross-sectional retrospective study of women (aged 15–46 years) diagnosed with SLE who were seen in various outpatient clinics at a large tertiary academic medical centre over a 2-year period. Demographic data were retrieved via the university-affiliated central data repository, and additional data, including documentation of contraception counselling, were obtained via manual chart abstraction. Univariable associations between variables and contraception counselling were assessed to produce unadjusted ORs and 95% CIs. Multivariable models were generated to evaluate independent associations between variables and contraception counselling.Results Data from 478 women (52% African American, 25% Caucasian) with SLE were included. Rheumatology was the subspecialty to document contraception counselling most frequently (57%). Nearly 80% of women received counselling from at least one subspecialty, 44% from at least two. Factors associated with having lower odds of receiving contraception counselling were older age and Caucasian race. Women on teratogenic medications (methotrexate, mycophenolate mofetil/mycophenolic acid, cyclophosphamide) had higher odds of receiving contraception counselling from at least one subspecialty (OR 2.01; 95% CI 1.23 to 3.26), from two or more subspecialties (OR 2.18; 95% CI 1.50 to 3.17), and from rheumatology (OR 1.86; 95% CI 1.27 to 2.73).Conclusions In this study, women with SLE on teratogenic medications had higher odds of receiving contraception counselling from rheumatology and from at least two subspecialties. Multidisciplinary approaches to enhance contraception counselling should be encouraged.

Objective To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods Associations of time‐dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community‐based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren‐Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time‐dependent knee injury history. Results At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3‐2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3‐2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4‐0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1‐2.1). DM was not associated with transitions of rKOA. Conclusion Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms.

Objective To describe point prevalence of knee symptoms, radiographic knee osteoarthritis (rKOA), severe rKOA, and symptomatic rKOA at four time points in the longitudinal, population‐based Johnston County Osteoarthritis Project (JoCo OA). Methods Data were from 2573 JoCo OA participants with up to 18 years of follow‐up (1999‐2018) and standardized fixed‐flexion knee radiographs read by a single, reliable expert musculoskeletal radiologist. The four outcomes were 1) self‐reported knee symptoms, defined by “On most days, do you have pain, aching, or stiffness in your right/left knee?”; 2) rKOA, defined as a Kellgren‐Lawrence grade (KLG) of 2 to 4); 3) severe rKOA, defined as a KLG of 3 or 4; and 4) symptomatic rKOA, defined as both symptoms and rKOA in the same joint. Weighted prevalence estimates and 95% confidence intervals (CIs) were generated overall and by age group, sex, race, and body mass index (BMI). Results Most recently (2017‐2018, T4), the overall prevalence (percentage) of knee symptoms, rKOA, severe rKOA, and symptomatic rKOA was 41% (95% CI: 35‐47%), 61% (95% CI: 56‐67%), 35% (95% CI: 30‐40%), and 30% (95% CI: 24‐35%), respectively. From time point T1 to T4, prevalence increased for rKOA, severe rKOA, and symptomatic rKOA but not for knee symptoms. The prevalence of both severe rKOA (17‐39%) and symptomatic rKOA (23‐30%) was consistently higher among women. The prevalence of all outcomes was higher among those with higher BMI and among Black participants at all time points, particularly rKOA (35‐69%) and severe rKOA (22‐46%). Conclusion These updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals.

BackgroundDuring the COVID-19 pandemic, the shift to virtual care became essential for the continued care of patients. Individuals with rheumatic and musculoskeletal diseases (RMDs) especially require frequent provider visits and close monitoring. To date, there have been limited studies examining inequities in health technology use among patients with RMDs. ObjectiveOur goal was to identify characteristics associated with patient portal use before and after the COVID-19 pandemic in a convenience sample of patients with RMDs from a large academic medical center. MethodsIn this cross-sectional study, Epic electronic medical record data were queried to identify established patients of the University of North Carolina Hospitals adult rheumatology clinic between November 1, 2017, through November 30, 2019. Demographic and clinical data were collected to compare MyChart (Epic’s patient portal) users with nonusers before and after the COVID-19 pandemic. MyChart activation and use were modeled using logistic regression and adjusted odds ratios, and confidence intervals were estimated. ResultsWe identified 5075 established patients with RMDs who met the inclusion criteria. Prior to the pandemic, we found that younger age (PUS $50,000 (P

The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.

We present allometric models for estimating total carbon content and above ground carbon (AGC) for the Arecaceae family, and for seven abundant neotropical palm species: the canopy species Socratea exorrhiza (n = 10) and Iriartea deltoidea (n = 10), the sub-canopy palm Euterpe precatoria (n = 10), and the understory species Asterogyne martiana (n = 15), Prestoea decurrens (n = 10), Geonoma interrupta (n = 10), and Chamaedorea tepejilote (n = 22). Understanding the allometry of functional groups such as palms is critical for improving carbon stocks estimates in tropical forests and determining how allometric differences affect species functional diversity. The research was carried out in the tropical rainforests of the Caribbean slope of Costa Rica. We harvested 87 palms of a wide range of sizes, and separated them into roots, stems, and leaves, measured their fresh and dry biomass, and calculated their carbon content, tissue density, and dry mass fraction (dmf). Our general palm model estimating total carbon content based on these seven species and 87 samples accounted for 92% of the variation across species. We generated a similar model to estimate AGC and explained 91% of the variation. We compared our AGC model with two models used to estimate palm carbon content: Goodman et al. (2013)’s and Chave et al. (2014)’s models and found that all three converged on the estimation of AGC although our model was the most parsimonious because it achieved the same efficiency with only two variables, stem diameter and stem height. To improve the accuracy of allometric models we need to incorporate more species, a greater diversity of growth forms, a wider range of sizes, a larger sample size, and more diversity of habitats dominated by palms. Estimating carbon content using allometric approaches could benefit from more consistency in data collection across plant groups.

Objective: To describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). Design: Data were from 3068 JoCoOA participants who attended up to five study visits (1991–2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: “On most days, do you have pain, aching, or stiffness in your right/left hip?“; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2–4; 3) severe rHOA: KLG of 3–4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45–54, 55–64, 65–74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5–24.9; 25–29.9; 30+ kg/m2). Results: At the most recent follow-up (2017–2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. Conclusion: These updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort.

Abstract Background The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. Methods BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. Results The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. Conclusions Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

Objective This study sought to develop and employ a comprehensive and standardized ultrasound (US) protocol and scoring atlas for the evaluation of features relevant to knee osteoarthritis (KOA) in a community‐based cohort in the United States, with the goals of demonstrating feasibility, reliability, and validity. Methods We utilized data from the fourth follow‐up (2016‐2018) of the Johnston County OA Project, which includes individuals with (~50%) and without radiographic KOA. All participants underwent standardized knee radiography and completed standard questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee US images were obtained by a trained sonographer using a standardized protocol and scored by trained rheumatologists using an atlas developed for this study. A total of 396 knees were each scored by two readers according to the atlas. Associations between US features, radiographic findings (graded by an expert radiologist), and KOOS scores were assessed. Results Overall interreader reliability for US scoring was fair to moderate. The strongest correlations between US and radiographic features were seen for osteophytes, and similarly strong correlations were seen between US osteophytes and overall radiographic Kellgren‐Lawrence Grade, demonstrating criterion validity. Features of effusion/synovitis and osteophytes were most associated with KOOS pain and impaired function. Conclusion US is a feasible, reliable, and valid method to assess features relevant to KOA in clinical and research settings. The protocol and atlas developed in this study can be utilized to evaluate KOA in a standardized fashion in future clinical studies, enabling greater utilization of this valuable modality in osteoarthritis.

Abstract Background We examined the association of three common chronic conditions (obesity, diabetes mellitus [DM], and cardiovascular disease [CVD]) with transitions among states of hip osteoarthritis (HOA). Methods This longitudinal analysis used data from the Johnston County Osteoarthritis Project (JoCo OA, n = 3857), a community-based study in North Carolina, USA, with 18.4 ± 1.5 years of follow-up. Transitions across the following states were modeled: development of radiographic HOA (rHOA; Kellgren-Lawrence grade [KLG] of 1 comorbidity, the likelihood of incident sxHOA increased, while that of symptom resolution significantly decreased. When stratified by sex, the association between obesity and incident symptoms was only seen in women; among men with DM versus men without, there was a significant (~ 75%) reduction in symptom resolution in those with rHOA. When stratified by race, African Americans with DM, versus those without, were much more likely to develop sxHOA. Conclusions Comorbid chronic conditions are common in individuals with OA, and these conditions have a significant impact on the persistence and progression of HOA. OA management decisions, both pharmacologic and non-pharmacologic, should include considerations of the inter-relationships between OA and common comorbidities such as DM and CVD.

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

Abstract INTRODUCTION In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center’s HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.

An increase in the severity of drought events on Mediterranean climates highlights the need of using plant material adapted to drought during restoration efforts. Thus, we investigated between-population morpho-physiological differences in Cryptocarya alba and Persea lingue, two native species from Mediterranean central Chile, for traits that could effectively discriminate population performance in response to water restriction (WR) testing. Three populations from each species were subjected to WR treatment and physiological, morphological, and growth parameters were assessed at the beginning and at the end of the experiment. In C. alba, the most xeric population displayed smaller plants with mesophyllous leaves and lower photosynthetic rates indicating a resource saving strategy. Moreover, the xeric population performed better during WR than the most mesic populations, exhibiting higher water use efficiency (iWUE) and maintenance of growth rates. All C. alba populations responded equally to WR in terms of morphology and biomass partitioning. In contrast, differences among P. lingue populations were subtle at the morpho-physiological level with no apparent relation to provenance environmental conditions, and no morphological traits were affected by WR. However, in response to WR application, the most mesic population was, as observed through reduction in relative growth rates, more affected than xeric populations. We attribute such discrete differences between P. lingue provenances to the lower distributional range of selected populations. Our results show that relative growth rates in both species, and iWUE only in C. alba, exhibited population specific responses upon WR imposition; these results correspond with the environmental conditions found at the origin of each populations. Both traits could further assist in the selection of populations for restoration according to their response to water stress.

The adoption of US culture among immigrants has been associated with higher leisure-time physical activity and sedentary behavior. However, most research to date assesses this association using single measures of acculturation and physical activity. Our objective was to describe the cross-sectional association between acculturation and both physical activity and sedentary behavior among US Hispanic/Latino adults. Participants included Hispanic/Latinos 18–74 years living in four US locations enrolled in the Hispanic Community Health Study/Study of Latinos from 2008 to 2011. Acculturation was measured using acculturation scales (language and social), years in the US, language preference, and age at immigration. Physical activity and sedentary behavior were measured using the Global Physical Activity Questionnaire (N = 15,355) and Actical accelerometer (N = 11,954). Poisson, logistic, and linear regression were used, accounting for complex design and sampling weights. English-language preference was positively associated with self-reported leisure-time and transportation physical activity and accelerometer-assessed moderate-to-vigorous physical activity (MVPA). Social acculturation was positively associated with self-reported leisure-time and transportation physical activity and MVPA. Years in the US and age at immigration were positively associated with accelerometer-assessed MVPA. Language acculturation, years in the US, and age at immigration were associated with occupational physical activity among those who reported employment. Most acculturation measures were associated with self-reported sitting but not with accelerometer-assessed sedentary behavior. Different measures of acculturation, capturing various domains acculturation, were associated with physical activity and sedentary behavior. However, the direction of the association was dependent on the measures of acculturation physical activity/sedentary behavior, highlighting the complexity of these relationships. Keywords: Physical activity, Acculturation, Hispanic, Latino, Sedentary behavior, Accelerometry

Abstract Background Osteoarthritis (OA) is associated with worsening physical function and a high prevalence of comorbid health conditions. In particular, cardiovascular disease (CVD) risk is higher in individuals with OA than the general population. Limitations in physical function may be one pathway to the development of CVD among individuals with OA. This study evaluated associations of symptomatic knee OA (sxKOA), baseline physical function and worsening of function over time with self-reported incident CVD in a community-based cohort. Methods Our sample consisted of individuals from the Johnston County Osteoarthritis Project who did not report having CVD at baseline. Variables used to evaluate physical function were the Health Assessment Questionnaire (HAQ), time to complete 5 chair stands, and the 8-ft walk. Worsening function for these variables was defined based on previous literature and cutoffs from our sample. Logistic regression analyses examined associations of sxKOA, baseline function and worsening of function over time with self-reported incident CVD, unadjusted and adjusted for relevant demographic and clinical characteristics. Results Among 1709 participants included in these analyses, the mean age was 59.5 ± 9.5 years, 63.6% were women, 15% had sxKOA, and the follow up time was 5.9 ± 1.2 years. About a third of participants reported worsening HAQ score, about two-fifths had worsened chair stand time, half had worsened walking speed during the 8-ft walk, and 16% self-reported incident CVD. In unadjusted analyses, sxKOA, baseline function, and worsening function were all associated with self-reported incident CVD. In multivariable models including all of these variables, sxKOA was not associated with incident CVD, but worsening function was significantly associated with increased CVD risk, for all three functional measures: HAQ odds ratio (OR) = 2.49 (95% confidence interval (CI) 1.90–3.25), chair stands OR = 1.58 (95% CI 1.20–2.08), 8-ft walk OR = 1.53 (95%CI 1.15–2.04). These associations for worsening function remained in models additionally adjusted for demographic and clinical characteristics related to CVD risk. Conclusions The association between symptomatic knee osteoarthritis and cardiovascular disease risk was explained by measures of physical function. This highlights the importance of physical activity and other strategies to prevent functional loss among individuals with symptomatic knee osteoarthritis.

En la región Pampeana Argentina, la simplificación de los agroecosistemas ha ocasionado la disminución de los servicios ecosistémicos, resultando en la pérdida de recursos, y afectando la calidad del suelo. Nuestro objetivo fue evaluar el efecto de la agriculturización en diferentes ambientes (subhúmedos y semiáridos) de la región Pampeana, mediante indicadores biológicos y el carbono orgánico edáfico. Durante 2013, 2014 y 2015, se evaluaron sitios correspondientes a las localidades de Río Cuarto, Rafael García, Manfredi y Marcos Juárez de la provincia de Córdoba, y un sitio en Villa Mercedes provincia de San Luis. En cada localidad se realizó un muestreo de suelo en un sitio de referencia y en diferentes secuencias de cultivos. Los parámetros evaluados fueron carbono de biomasa microbiana (CBM), respiración microbiana (RM), coeficiente metabólico (qCO2), actividades enzimáticas de hidrólisis del diacetato de fluoresceína (FDA), fosfatasa ácida (FA) y deshidrogenasa (DHG), carbono orgánico total (COT) del suelo y coeficiente microbiano (qMic). Los resultados obtenidos expresaron que las variables más relevantes para actuar como indicadores de calidad de suelo fueron CBM y COT, junto a las enzimas FDA y FA, ya que registraron en la mayoría de los sitios diferencias significativas entre tratamientos. En general esos indicadores permitieron diferenciar los suelos de monte nativo respecto de los de uso antrópico. A su vez, los valores obtenidos mediante la aplicación del índice de calidad de suelos fueron significativamente mayores en las situaciones naturales, sin observarse diferencias entre las secuencias de cultivos.

Pregnancy Associated Breast Cancer is defined as breast cancer that is diagnosed during pregnancy or within the first postpartum year. The incidence of breast cancer during pregnancy is about 1 in 3,000 pregnancies making breast cancer the second most common in pregnancy malignancy, breast cancer during pregnancy is a complex circumstance all the implications of the fetus can cause cancer treatment. It should be enough information to not delay diagnosis and adequately treat patients, this should be supported by multidisciplinary group. The goal of care for women with breast cancer and pregnancy is the local disease control and prevention of metastasis. There is a shortage of prospective studies regarding the diagnosis and treatment of breast cancer during pregnancy. General pregnancy knowledge about the clinical - pathological and oncological and perinatal outcome of patients with pregnancy and breast cancer therefore is very important. In this article, we reviewed the current literature in order to generate greater awareness regarding this disease and to optimize the management and reduce the delay in diagnosing women with pregnancy associated breast cancer. The objective of this review of the literature is to describe the characteristics of breast cancer associated with pregnancy and therapeutic advances regarding this disease. A literature review of articles indexed systematically in PubMed was carried out.

Background: Breast cancer (BC) is the most common cancer afflicting Puerto Rican women and accounts for more cancer-related deaths in this population than any other cancer. Methods: Demographic, anthropometric, family history, and lifestyle data, as well as DNA repair capacity (DRC), were compared in 465 BC cases and 661 controls. Crude and multiple logistic regression-derived adjusted odds ratios were used as indicators of the associations between BC and the variables under study. Results: A low DRC level, aging (>61 years), family history of BC, and low education level had statistically significant associations with increased BC risk. Endometriosis, full-term pregnancy at an earlier age, higher parity, hysterectomy before age 50, multivitamin and calcium intake, and longer duration of breastfeeding significantly decreased BC risk. Conclusions: This study discusses the major risk factors for BC in Puerto Rico (PR). Because many of these findings represent modifiable risk factors, they can translate into public health initiatives to lower BC risk. In addition, the possibility of using DRC as a simple screening tool for BC risk is explored.

El cambio climático es un fenómeno global con consecuencias irreversibles si no se toman las acciones pertinentes. En Latinoamérica, el cambio climático no recibe la atención merecida en la agenda política, académica ni ciudadana, consecuentemente, la información en español e investigaciones acerca de esta temática son limitadas. El I Simposio sobre cambio climático y Biodiversidad, realizado en agosto del año 2017, en Costa Rica, frente a una audiencia multidisciplinaria e interinstitucional, buscó generar interés y discusión sobre posibles soluciones ante el cambio climático en esta región. El simposio se organizó según cuatro ejes temáticos: 1) Impactos sobre ecosistemas, 2) Mitigación, 3) Adaptación, y 4) Comunicación y enseñanza del cambio climático. En esta publicación, desarrollamos una síntesis crítica de los diversos temas tratados en dicho simposio, algunos de los cuales se desarrollan en mayor profundidad en este número especial de UNED Research Journal. No cabe duda de que el cambio climático es real y tiene su origen en las actividades humanas, lo que implica que debemos cambiar nuestras acciones individuales y decisiones políticas para reducir la emisión e incrementar la mitigación de gases de efecto invernadero, así como para adaptarnos a la nueva realidad que este fenómeno implica.

Traditional applanation tonometry techniques lack the necessary accuracy and reliability for measuring the intraocular pressure (IOP), and there is still a need for a reliable technique for in vivo diagnosis. A single laser-induced cavitation bubble event was optically monitored in order to precisely measure the first collapse time of the cavitation bubble, which presents a direct dependence on the liquid pressure. This can certainly be done within the IOP range. We now extend the partial transmittance modulation (STM) technique to determine its feasibility for directly measuring the IOP by studying the nanosecond (ns) pulsed laser-induced cavitation bubble dynamics for an externally pressurized fresh ex vivo porcine eye. The results demonstrate that it is possible to monitor the IOP by detecting the light of a continuous-wave (CW) laser beam which is intensity modulated by the bubble itself. This technique currently presents a measurement resolution of about 4 mmHg in the 5 to 50 mmHg pressure range, indicating the feasibility of this approach for measuring IOP. This technique provides a direct measurement within the anterior eye chamber, avoiding common pitfalls in IOP diagnosis, such as errors due to patient movement, varying physical properties of the eye globe, or central cornea thickness (CCT) effects.

Multidrug efflux pumps constitute a category of antibiotic resistance determinants that are a part of the core bacterial genomes. Given their conservation, it is conceivable that they present functions beyond the extrusion of antibiotics currently used for therapy. Pseudomonas aeruginosa stands as a relevant respiratory pathogen, with a high prevalence at hospitals and in cystic fibrosis patients. Part of its success relies on its low susceptibility to antibiotics and on the production of virulence factors, whose expression is regulated in several cases by quorum sensing (QS). We found that overexpression of the MexCD-OprJ multidrug efflux pump shuts down the P. aeruginosa QS response. Our results support that MexCD-OprJ extrudes kynurenine, a precursor of the alkyl-quinolone signal (AQS) molecules. Anthranilate and octanoate, also AQS precursors, do not seem to be extruded by MexCD-OprJ. Kynurenine extrusion is not sufficient to reduce the QS response in a mutant overexpressing this efflux pump. Impaired QS response is mainly due to the extrusion of 4-hydroxy-2-heptylquinoline (HHQ), the precursor of the Pseudomonas Quinolone Signal (PQS), leading to low PQS intracellular levels and reduced production of QS signal molecules. As the consequence, the expression of QS-regulated genes is impaired and the production of QS-regulated virulence factors strongly decreases in a MexCD-OprN P. aeruginosa overexpressing mutant. Previous work showed that MexEF-OprJ, another P. aeruginosa efflux pump, is also able of extruding kynurenine and HHQ. However, opposite to our findings, the QS defect in a MexEF-OprN overproducer is due to kynurenine extrusion. These results indicate that, although efflux pumps can share some substrates, the affinity for each of them can be different. Although the QS response is triggered by population density, information on additional elements able of modulating such response is still scarce. This is particularly important in the case of P. aeruginosa lung chronic infections, a situation in which QS-defective mutants are accumulated. If MexCD-OprJ overexpression alleviates the cost associated to triggering the QS response when un-needed, it could be possible that MexCD-OprJ antibiotic resistant overproducer strains might be selected even in the absence of antibiotic selective pressure, acting as antibiotic resistant cheaters in heterogeneous P. aeruginosa populations.

Electroencephalography (EEG) is the standard diagnosis method for a wide variety of diseases such as epilepsy, sleep disorders, encephalopathies, and coma, among others. Resting-state functional magnetic resonance (rs-fMRI) is currently a technique used in research in both healthy individuals as well as patients. EEG and fMRI are procedures used to obtain direct and indirect measurements of brain neural activity: EEG measures the electrical activity of the brain using electrodes placed on the scalp, and fMRI detects the changes in blood oxygenation that occur in response to neural activity. EEG has a high temporal resolution and low spatial resolution, while fMRI has high spatial resolution and low temporal resolution. Thus, the combination of EEG with rs-fMRI using different methods could be very useful for research and clinical applications. In this article, we describe and show the results of a new methodology for processing rs-fMRI using seeds positioned according to the 10-10 EEG standard. We analyze the functional connectivity and adjacency matrices obtained using 65 seeds based on 10-10 EEG scheme and 21 seeds based on 10-20 EEG. Connectivity networks are created using each 10-20 EEG seeds and are analyzed by comparisons to the seven networks that have been found in recent studies. The proposed method captures high correlation between contralateral seeds, ipsilateral and contralateral occipital seeds, and some in the frontal lobe.

ABSTRACT It is generally assumed that the acquisition of antibiotic resistance is associated with a fitness cost. We have shown that overexpression of the MexEF-OprN efflux pump does not decrease the fitness of a resistant Pseudomonas aeruginosa strain compared to its wild-type counterpart. This lack of fitness cost was associated with a metabolic rewiring that includes increased expression of the anaerobic nitrate respiratory chain when cells are growing under fully aerobic conditions. It was not clear whether this metabolic compensation was exclusive to strains overexpressing MexEF-OprN or if it extended to other resistant strains that overexpress similar systems. To answer this question, we studied a set of P. aeruginosa mutants that independently overexpress the MexAB-OprM, MexCD-OprJ, or MexXY efflux pumps. We observed increased expression of the anaerobic nitrate respiratory chain in all cases, with a concomitant increase in NO3 consumption and NO production. These efflux pumps are proton/substrate antiporters, and their overexpression may lead to intracellular H+ accumulation, which may in turn offset the pH homeostasis. Indeed, all studied mutants showed a decrease in intracellular pH under anaerobic conditions. The fastest way to eliminate the excess of protons is by increasing oxygen consumption, a feature also displayed by all analyzed mutants. Taken together, our results support metabolic rewiring as a general mechanism to avoid the fitness costs derived from overexpression of P. aeruginosa multidrug efflux pumps. The development of drugs that block this metabolic “reaccommodation” might help in reducing the persistence and spread of antibiotic resistance elements among bacterial populations. IMPORTANCE It is widely accepted that the acquisition of resistance confers a fitness cost in such a way that in the absence of antibiotics, resistant populations will be outcompeted by susceptible ones. Based on this assumption, antibiotic cycling regimes have been proposed in the belief that they will reduce the persistence and spread of resistance among bacterial pathogens. Unfortunately, trials testing this possibility have frequently failed, indicating that resistant microorganisms are not always outcompeted by susceptible ones. Indeed, some mutations do not result in a fitness cost, and in case they do, the cost may be compensated for by a secondary mutation. Here we describe an alternative nonmutational mechanism for compensating for fitness costs, which consists of the metabolic rewiring of resistant mutants. Deciphering the mechanisms involved in the compensation of fitness costs of antibiotic-resistant mutants may help in the development of drugs that will reduce the persistence of resistance by increasing said costs.

Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse) favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan (n=30) and Brazil (n=10). These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease (n=221). The diseases most frequently reported were ATLL (114 families) and HAM/TSP (101 families). Most families (n=142) included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2% to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1% to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an affected parent with one or more affected children. The evidence in the literature, although weak, does suggest that HTLV-1-associated diseases sometimes cluster in families. Whether familial transmission of HTLV-1 is the only determining factor, or whether other factors are also involved, needs further research.

HIV-1 M originated from SIVcpz endemic in chimpanzees from southeast Cameroon or neighboring areas, and it started to spread in the early 20th century. Here we examine the factors that may have contributed to simian-to-human transmission, local transmission between humans, and export to a city. The region had intense ape hunting, social disruption, commercial sex work, STDs, and traffic to/from Kinshasa in the period 1899–1923. Injection treatments increased sharply around 1930; however, their frequency among local patients was far lower than among modern groups experiencing parenteral HIV-1 outbreaks. Recent molecular datings of HIV-1 M fit better the period of maximal resource exploitation and trade links than the period of high injection intensity. We conclude that although local parenteral outbreaks might have occurred, these are unlikely to have caused massive transmission. World War I led to additional, and hitherto unrecognized, risks of HIV-1 emergence. We propose an Enhanced Heterosexual Transmission Hypothesis for the origin of HIV-1 M, featuring at the time and place of its origin a coincidence of favorable co-factors (ape hunting, social disruption, STDs, and mobility) for both cross-species transmission and heterosexual spread. Our hypothesis does not exclude a role for parenteral transmission in the initial viral adaptation.

INTRODUCTION: Prevalence and detection rates of leprosy are not sufficient to show the real magnitude of changes in epidemiological patterns. OBJECTIVES: Evaluate the feasibility and usefulness of the proportion of new leprosy patients with a single skin lesion (SSL) as a potential indicator of the elimination of leprosy. METHODS: We conducted a retrospective study based on secondary data analyzing newly reported cases of leprosy between 1997 and 2002, in the city of Palmas, Tocantins, Brazil. Patients with a single lesion were compared to remaining patients, and the odds ratio was used as measure of association. RESULTS: Out of the 1,303 new cases of leprosy, 481 (36.9%) had a SSL. An increasing time-trend was observed in the proportion of new cases detected with a single lesion, which grew from 20.3% in 1999 to 49.1% in 2002 (linear trend pINTRODUÇÃO: As taxas de detecção e prevalência de hanseníase não são suficientes para mostrar a real magnitude de mudanças nos padrões epidemiológicos da doença. OBJETIVOS: Avaliar a aplicabilidade e utilidade da medida de proporção de casos de hanseníase com lesão única de pele como potencial indicador de avaliação do progresso da eliminação da hanseníase em áreas hiperendêmicas. METODOLOGIA: Estudo retrospectivo baseado na análise de dados secundários de casos novos de hanseníase notificados entre 1997 e 2002 na cidade de Palmas, estado de Tocantins, Brasil. Os registros de pacientes com lesão única foram comparados àqueles registrados com mais de uma lesão. Odds ratio foi utilizado como medida de associação. RESULTADOS: De um total de 1.303 casos novos de hanseníase notificados, 481 (36,9%) apresentavam lesão única de pele. Verificou-se tendência de incremento na proporção de casos de casos novos diagnosticados com lesão única variando de 20,3% em 1999 para 49,1% em 2002 (p < 0,001), simultaneamente à redução do registro de número de casos novos após 1999. Maior proporção de pacientes com lesão única de pele foi verificada em pacientes do sexo feminino, menores de 15 anos, paucibacilares nas formas clínicas tuberculóide e indeterminada, com baciloscopia negativa, com lesões do tipo mácula, sem incapacidades físicas e diagnosticados em unidades básicas de saúde. CONCLUSÕES: Os resultados confirmam que a proporção de pacientes com lesão única de pele pode ser utilizada como indicador na avaliação do progresso da eliminação da hanseníase em áreas hiperendêmicas.

En este trabajo se describe una nueva especie de thrips de suelo para Adraneothrips Hood, 1925 de Costa Rica. Se provee una clave de identificación para las especies de América Central.A new species of Adraneothrips Hood, 1925, soil Thysanoptera, is described from Costa Rica. A key for the recognition of the species of Central America is provided.

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the "noise" from 6-12 non-causal SNPs will cancel out the "signal" of one causal SNP across five popular gene-based tests. Furthermore, we find complex and differing behavior of the methods in the presence of LD within and between non-causal and causal SNPs. Ultimately, better approaches for a priori prioritization of potentially causal SNPs (e.g., predicting functionality of non-synonymous SNPs), application of these methods to sequenced or fully imputed datasets, and limited use of window-based methods for assigning inter-genic SNPs to genes will improve power. However, significant power loss from non-causal SNPs may remain unless alternative statistical approaches robust to the inclusion of non-causal SNPs are developed.

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called "DivE" was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1⁺ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1⁺ clones.

BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.

Resumen: En los últimos años se ha producido un importante incremento del número de personas que viaja a todos los puntos del mundo, incluyendo países exóticos. Así alrededor de 10 millones de personas, desde inmigrantes y turistas hasta diplomáticos y empresarios, se mueven anualmente entre Europa y los llamados países del tercer mundo. Debido a estos movimientos de población ha aumentado el riesgo de padecer no sólo enfermedades de distribución cosmopolita como Tuberculosis, Hepatitis, SIDA, ETS, etc si no también enfermedades tropicales y otras derivadas de los cambios de clima y alimentación. Sin duda la cifra más elevada de personas que acude a los Centros de salud o bien a los Centros de Vacunación Internacional dependientes de los Servicios de Sanidad Exterior antes de emprender un viaje son los turistas, pero hay que tener en cuenta que bajo la definición de turista se encuentran viajeros cuyos riesgos son muy dispares, ya que hay diferencias sustanciales entre los viajes organizados que siguen rutas turísticas preestablecidas y aquellos viajeros que se adentran en zonas recónditas o aquellos que practican el turismo deportivo: trekking, escalada, rafting, etc. Por ello el objetivo principal de este trabajo es aportar una serie de conocimientos básicos en relación a los viajes turísticos, vacunaciones, y sanidad exterior. Abstract: In the last few years it is taking place an important increment of the number of people who travel all over the world, including exotic countries. In this way, about 10 million people, including both immigrants and tourist and diplomatic and businessmen, move annually among Europe and the so-called countries of the third world. Due to these population´s movements it has been increased the risk of suffering not only from diseases of cosmopolitan distribution like Tuberculosis, Hepatitis, AIDS, ETS, etc but also tropical diseases and another ones derived from the changes of climate and nutrition. Undoubtedly, the majority of people who goes to the Health Centre or to the International vaccination Centres dependent on the foreign Health Services before beginning a journey are tourists, but it is necessary to consider than under the definition of tourist are travellers with different risks, because there are substantial differences among the package tours that follow already-established tourist routes and those travellers who go into recondite zones or those who practice the sports tourism: Trekking, climbing, rafting, etc. Hence the main objective of this article is to contribute some basic knowledge in relation to tourist journeys, vaccinations, and foreign health. Centro de Trabajo: Hospital Central de Asturias y Hospital Princesa Sofía (León) Fecha del Trabajo: 01/06/2004 Palabra Clave: Vacunas, viajes, Sanidad Exterior Key Words: Vaccines, journeys, Foreign Heatlh.

La infección con VHC es la causa más común de hepatitis viral crónica en EE.UU (1). En nuestra ciudad no se ha realizado ninguna evaluación de las características genotípicas del VHC. Nuestro propósito fue describir los genotipos en un grupo de pacientes con infección por VHC en Medellín y determinar su relación con algunas variables epidemiológicas.

Se conoce muy poco sobre la prevalencia de anti-VHA en lapoblación de Medellín. En 1997 se realizó un estudio en los estratos 1-2-3, encontrando una prevalencia del 93.5% para niños de 3-6 años (1). Esto nos sirve de referencia para completar el patrón epidemiológico de prevalencia en los estratos faltantes que son 4-5-6, ampliando el grupo de estudio hasta los 30 años y así conocer la distribución por sexo, estratos socioeconómicos y edad. Nuestro objetivo es determinar la prevalencia de anti-VHA en menores de 30 años discriminada por grupos de edad de los estratos 4-5-6.

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches. Additionally, we discuss future directions of the UCLA Cell Exchange program to support histocompatibility testing to adapt to the fast-evolving field of immunotherapy, tolerance and xenotransplantation. [ABSTRACT FROM AUTHOR]