Decay kinetics of HIV-1-RNA in seminal plasma with dolutegravir/lamivudine versus dolutegravir plus emtricitabine/tenofovir alafenamide in treatment-naive people living with HIV.

BACKGROUND: This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. METHODS: Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. RESULTS: Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30-5.43) and 4.76 (4.09-5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). CONCLUSIONS: After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.

Screening of regulated aromatic amines in clothing marketed in Brazil and Spain: Assessment of human health risks.

Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.

Clothing as a potential exposure source of trace elements during early life.

In recent years, the interest in determining the chemical composition of textile products has increased among the scientific community and regulatory agencies, driven by toxicological issues and environmental concerns. Chemical elements are naturally present in clothing as natural fibers or intentionally added during manufacture. Some of them show physical-chemical properties that allow their absorption through the skin. In addition, chronic situations increase the dermal exposure capacity. Because of age-specific behavioral characteristics and underdeveloped physiological function, children may be especially sensitive to exposure to trace elements. This study aimed to analyze the levels of twenty trace elements in 120 clothing items commercialized in Spain. Textile products for pregnant women and children <36 months old were included. The potential health implication of this dermal exposure in early life was also evaluated. Aluminum, zinc, and titanium showed the highest concentrations, with median levels of 27.6, 5.6, and 4.2 mg/kg, respectively. Since chromium is employed as a metal complex dye in synthetic fibers, high levels of this element were found in black polyester. Dermal exposure to titanium, which is a ubiquitous element in clothes made of synthetic fibers, was associated with a hazard quotient (HQ) higher than the threshold value (HQ > 1), with values of 1.13 for pregnant women and 1.22 for newborns. On the other hand, HQ values of other elements and cancer risks were lower than the recommended values. Assessing early-life exposure to toxic elements can help to identify potential sources and to prevent or reduce human exposure, mainly in vulnerable groups.

Sex-comparative study of gambling disorder regarding alexithymia and symptoms of depression, anxiety and hostility.

BACKGROUND AND AIMS: Alexithymia and psychological symptomatology have been closely associated with gambling disorder (GD). However, sex differences remain underexplored. This study aims, firstly, to explore the differences between groups (GD and no-GD) and sexes (women vs. men) in alexithymia and psychological symptomatology (depression, anxiety and hostility). Secondly, the relationship between alexithymia and psychological symptomatology was analysed by gambling and sex groups. Thirdly, it examines the moderation role of sex and gambling in the relationship between alexithymia and each psychological symptom. METHOD: The sample was composed of 80 people with GD diagnosis and 80 without GD (40 women and 40 men in each group). RESULTS: The results showed that alexithymia is positively related to depression, anxiety and hostility, with significantly higher scores in people with GD. Moderation analyses showed a threefold interaction, in which higher alexithymia was related to higher depression for men with GD but not for GD-women. However, in women with GD, depression levels are higher than in people without GD and tend to be more stable over time, despite the lack of effect of alexithymia. CONCLUSIONS: These results provide evidence indicating that dysfunctional psychological symptomatology affects people with GD to a greater extent than people without GD, but also that the aetiology and effect of underlying vulnerability factors on gambling is different according to sex. The need of prevention and treatment programmes that consider different psychological aspects depending on sex is reinforced.

Problematic Gambling Behavior in a Sample with Substance Use Disorder: The Role of Attachment Style and Alexithymia.

Gambling disorder is a high comorbid disorder in substance abusers which conjunct appearance is related to worse symptomatology and evolution. Nevertheless, the research on the risk factors that may explain this comorbidity is scarce. We build of the self-regulation theory of attachment and addiction to examine if insecure attachment is related to gambling comorbidity in substance abuse disorder and the mediating role of alexithymia in this process. A cross-sectional study was carried out with 369 clinical patients with substance use disorder of which 69 presented comorbid gambling disorder diagnosed with the DSM-5 criteria. Results showed that insecure attachment was more prevalent in the group with comorbid gambling. In this group, the alexithymia levels were also higher and mediated the relationship in between attachment and gambling disorder comorbidity even controlling for several sociodemographic variables. This research indicates that insecure attachment enhances the risk of gambling comorbidity on substance abusers due to the detrimental effect on the self-regulation of emotion. Thus, interventions directed to increase the identification, expression and awareness of emotions might help to reduce comorbidity of gambling of substance use disorders.

The efficacy of postdivorce intervention programs for children: A meta-analytical review.

Preventive postdivorce interventions aim to help children cope with divorce and promote their adjustment. Nevertheless, questions remain regarding the concrete outcomes of these interventions and the intervention characteristics that influence them. This meta-analysis of 30 studies analyzes the efficacy of postdivorce interventions on children's symptomatology, personal resources, and adaptation to divorce. Likewise, it explores whether the intervention impacts the putative mediators from the family context and whether the characteristics of the studies themselves also influence the results. Using a data set of N = 4344 individuals, 258 effect sizes were calculated. Random effects analyses evidenced the impact of the interventions on specific variables instead of on children's global adjustment. There were no significant effects on children's mental health outcomes, and none of these effects were qualified by the moderators that were examined. Preventive postdivorce interventions had significant effects, specifically on children's divorce adjustment and self-esteem. The study of the moderators found that the interventions were generally homogeneous, and only one of the 20 moderators examined had a significant effect. Based on children's age, the interventions had an impact on family functioning only when they involved younger children, but this result should be interpreted with caution due to the small sample of studies. This meta-analysis provides evidence of the relevance of postdivorce interventions to critical variables as well as information about the role of the intervention characteristics in the effects and makes suggestions for future research on divorce interventions that encompass both practical and empirical developments.

Non-regulated aromatic amines in clothing purchased in Spain and Brazil: Screening-level exposure and health impact assessment.

The staggering amount of chemicals in clothes and their harmful effects on human health and the environment have attracted the attention of regulatory agencies and the scientific community worldwide. Azo dyes are synthetic dyestuffs with widespread use in textile industries, currently classified as emerging pollutants of great health concern to consumers. These compounds may release one or more aromatic amines (AAs) after reductive cleavage of their azo bounds. Twenty-two AAs have already been regulated due to their carcinogenic effects. However, since information on their potential toxicity is not currently available, several AAs have not been still regulated by the European Union. Considering this gap, the present study aimed to assess the levels of forty non-regulated AAs in 240 clothing items from Spain and Brazil. The potential impact on the health of vulnerable population groups after dermal exposure to those garments was also evaluated. In Brazil, at least one AA was detected in the clothes, while in samples obtained in Spain, only two of them showed values below the limit of detection for AAs. In 75 clothes, at least one of the measured AAs was higher than the hazardous threshold (30 mg/kg), which can mean risks to human health since these compounds are suspected to be mutagenic. Aniline, the most common AA, showed a high detection rate (82%) in clothes, with significantly higher concentrations in items commercialized in Brazil (0.35 vs. 0.17 mg/kg; p = 0.032). Moreover, o-aminobenzenesulfonic and p-phenylenediamine, suspected mutagenic, were found at relevant concentrations in several clothes, mainly made of synthetic fibers. In this study, the hazard index associated with exposure to AAs through clothing was low (0.006-0.13) for all the population groups of both countries in the medium-bound scenario. However, its value was close to 1 for Brazilian pregnant women (0.998) when the maximum concentration value was considered under an upper-bound scenario. The risk of exposure to non-regulated AAs may be underestimated since only dermal exposure was considered for risk assessment. Moreover, the co-occurrence of other carcinogenic and non-carcinogenic substances present in skin-contact clothes should mean an additional source of potential risk.

Buying-shopping disorder, impulsivity, emotional dependence and attachment in adolescents.

In recent years, several studies have shown that the incidence of buying-shopping disorder (BSD) is increasing. Impulsivity is one of the factors involved in its aetiology and is related to emotional dependence. In addition, early affective deprivation may trigger emotional dependence. The aims of the present study weresal: to compare the types of attachment, levels of emotional dependence, impulsivity and BSD according to sex; to determine whether the proposed relational model is fulfilled; and analyse possible differences in this model in terms of the sample's sex. The sample consisted of 1498 adolescents (53.8% men and 46.2% women) from Ecuador whose age ranged from 14 to 18 years (M = 15.77, SD = 1.21). The results showed that a preoccupied attachment style is indirectly related to a higher risk of BSD due to emotional dependence when impulsivity levels are medium or high because emotional dependence is moderated by impulsivity. The study variables are related in the same way in men and women but boys show higher levels of preoccupied attachment, impulsivity, emotional dependence and BSD. This study gives us a clearer picture of how these variables are related and provides information that could be of great use in assisting people with BSD. This knowledge could be applied to improve both the treatment and prevention of this problem.

Psychological responses to COVID-19 in a Mexican population: an exploratory study during second and third phases.

This work constitutes an exploratory study during the second and third phases of COVID-19 in Mexico, characterized by local transmission and untraceable cases, respectively, with an incidental sample of 666 participants. The 21-item Depression Anxiety Stress Scale was used to assess depression, anxiety and stress associated to COVID-19. Additionally, the Impact of the Event Scale-Revised was applied to assess the impact of the event, and the 10-item Connor-Davidson Resilience Scale was employed to assess resilience. Participants' levels of traumatic impact (21.7%), severe depression (7%), severe anxiety (9.4%) and severe stress (5.4%) were revealed to be lower than other populations. Comparison of means and effect size η2p of the data shows that women and young people (18-39 years) suffer the greatest negative effects. Individuals with higher levels of resilience experience fewer psychological consequences confirming its importance in the face of the adversities. These findings provide valuable information on the impact of COVID-19 pandemic in the Mexican population, allowing a comparative analysis at an international level which can be helpful in the development of appropriate sanitary policies.

Genomic Chaos (Multiple Copy Number Variations and Structural Reorganization) Detected in Two Prenatal Cases.

The use of new technologies in the routine diagnosis of constitutional abnormalities, such as high-resolution chromosomal microarray and next-generation sequencing, has unmasked new mechanisms for generating structural variation of the human genome. For example, complex chromosome rearrangements can originate by a chromosome catastrophe phenomenon in which numerous genomic rearrangements are apparently acquired in a single catastrophic event. This phenomenon is named chromoanagenesis (from the Greek "chromo" for chromosome and "anagenesis" for rebirth). Herein, we report 2 cases of genomic chaos detected at prenatal diagnosis. The terms "chromothripsis" and "chromoanasynthesis" and the challenge of genetic counseling are discussed.

Measuring Perceptions of the Therapeutic Alliance in Individual, Family, and Group Therapy from a Systemic Perspective: Structural Validity of the SOFTA-s.

This study examined the multidimensional structure of the client and therapist versions of the self-report measure, System for Observing Family Therapy Alliances (SOFTA-s; Friedlander, Escudero, & Heatherington, Therapeutic alliances in couple and family therapy: An empirically informed guide to practice. Washington, DC: American Psychological Association, 2006) across three distinct therapeutic modalities (individual, family, group). Specifically, we investigated whether the originally theorized model of four first-order factors (Engagement in the Therapeutic Process, Emotional Connection with the Therapist, Safety within the Therapeutic System, and Shared Sense of Purpose within the Family) would be reflected in a second-order factor (Therapeutic Alliance). The sample included 105 therapists who worked with 858 clients (165 individuals, 233 families, and 43 groups) in several Spanish community agencies. To control for dependent data, we used multilevel modeling. Results of the multilevel confirmatory factor analyses showed adequate reliabilities, fit indices, and factor loadings across the three therapy contexts for both versions of the measure (client and therapist). Adequate measurement invariance was also found across respondents and therapy modalities. Taken together, these results support the structural validity of the SOFTA-s, a brief and flexible self-report alliance measure that can be used reliably in clinical practice as well as in studies of individual, family, and group therapy.

Este estudio examinó la estructura multidimensional de las versiones del paciente y del terapeuta de la herramienta de medición por autoinforme, "Sistema de Observación de Alianza Terapéutica en Intervención Familiar" (System for Observing Family Therapy Alliances, SOFTA-s; Friedlander, Escudero, & Heatherington, 2006) entre tres modalidades terapéuticas diferentes (individual, familiar, grupal). Específicamente, investigamos si el modelo teorizado originalmente de cuatro factores de primer orden (participación en el proceso terapéutico, conexión emocional con el terapeuta, seguridad dentro del sistema terapéutico y un objetivo en común dentro de la familia) se reflejaría en un factor de segundo orden (alianza terapéutica). La muestra consistió en 105 terapeutas que trabajaron con 858 pacientes (165 individuos, 233 familias y 43 grupos) en varios organismos de comunidades españolas. Para evaluar los datos dependientes, utilizamos el modelo multinivel. Los resultados de los análisis factoriales confirmatorios multinivel demostraron fiabilidades, índices de ajuste y cargas factoriales adecuadas entre los tres contextos de terapia para ambas versiones de la herramienta de medición (paciente y terapeuta). También se halló una invariancia de medición adecuada entre los encuestados y las modalidades de terapia. En conjunto, estos resultados respaldan la validez estructural del SOFTA-s, una herramienta de medición de la alianza breve y flexible por autoinforme que puede utilizarse de manera fiable en la práctica clínica, así como en estudios de la terapia individual, familiar y grupal. Este estudio examinó la estructura multidimensional de las versiones del paciente y del terapeuta de la herramienta de medición por autoinforme, "Sistema de Observación de Alianza Terapéutica en Intervención Familiar" (System for Observing Family Therapy Alliances, SOFTA-s; Friedlander, Escudero, & Heatherington, 2006) entre tres modalidades terapéuticas diferentes (individual, familiar, grupal). Específicamente, investigamos si el modelo teorizado originalmente de cuatro factores de primer orden (participación en el proceso terapéutico, conexión emocional con el terapeuta, seguridad dentro del sistema terapéutico y un objetivo en común dentro de la familia) se reflejaría en un factor de segundo orden (alianza terapéutica). La muestra consistió en 105 terapeutas que trabajaron con 858 pacientes (165 individuos, 233 familias y 43 grupos) en varios organismos de comunidades españolas. Para evaluar los datos dependientes, utilizamos el modelo multinivel. Los resultados de los análisis factoriales confirmatorios multinivel demostraron fiabilidades, índices de ajuste y cargas factoriales adecuadas entre los tres contextos de terapia para ambas versiones de la herramienta de medición (paciente y terapeuta). También se halló una invariancia de medición adecuada entre los encuestados y las modalidades de terapia. En conjunto, estos resultados respaldan la validez estructural del SOFTA-s, una herramienta de medición de la alianza breve y flexible por autoinforme que puede utilizarse de manera fiable en la práctica clínica, así como en estudios de la terapia individual, familiar y grupal.

Urine metabolomic analysis for monitoring internal load in professional football players.

INTRODUCTION: The design of training programs for football players is not straightforward due to intra- and inter-individual variability that leads to different physiological responses under similar training loads. OBJECTIVE: To study the association between the external load, defined by variables obtained using electronic performance tracking systems (EPTS), and the urinary metabolome as a surrogate of the metabolic adaptation to training. METHODS: Urine metabolic and EPTS data from 80 professional football players collected in an observational longitudinal study were analyzed by ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry and assessed by partial least squares (PLS) regression. RESULTS: PLS models identified steroid hormone metabolites, hypoxanthine metabolites, acetylated amino acids, intermediates in phenylalanine metabolism, tyrosine, tryptophan metabolites, and riboflavin among the most relevant variables associated with external load. Metabolic network analysis identified enriched pathways including steroid hormone biosynthesis and metabolism of tyrosine and tryptophan. The ratio of players showing a deviation from the PLS model of adaptation to exercise was higher among those who suffered a muscular lesion compared to those who did not. CONCLUSIONS: There was a significant association between the external load and the urinary metabolic profile, with alteration of biochemical pathways associated with long-term adaptation to training. Future studies should focus on the validation of these findings and the development of metabolic models to identify professional football players at risk of developing muscular injuries.

Human exposure to trace elements, aromatic amines and formaldehyde in swimsuits: Assessment of the health risks.

Nowadays, most of the swimsuits are mainly made of artificial fibres, which have interesting properties such as water repellence and fast drying. Swimsuits contain a wide range of additives, which can mean a hazard for the environment and/or human health. In this study, the concentrations of formaldehyde (free and water soluble), 24 aromatic amines, and 28 trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were analysed in 39 swimsuits covering a wide range of materials, colours and brands. Dermal exposure and health risks were assessed for adults (men and women) aged > 18 years old, babies between 2 and < 3 years old, children (boys and girls) between 3 and < 6 years old and 6 and < 11 years old, and teenagers (boys and girls) between 11 and < 16 years old, wearing swimsuits for 4 h or 8 h. Formaldehyde and aromatic amines were below their respective detection limits in all samples (<16 and < 1.5 mg/kg, respectively). Regarding trace elements, Ti showed the highest mean levels (1844 mg/kg), being significantly higher in polyamide (3759 mg/kg) than in polyester (24.1 mg/kg) swimsuits. These high Ti levels were confirmed by environmental scanning electron microscope in a single sample made of polyamide. Increased concentrations of Cr were also observed, but only in polyamide black fabrics, with values ranging from 624 to 932 mg/kg. Non-cancer risks (hazard quotients) derived from the exposure to trace elements were in a safe zone for all analysed trace elements. Furthermore, the carcinogenic risks were evaluated for As, Cr and Pb, exhibiting values below the 10-5 threshold, with the exception of Cr in babies and children-girls. For Ti, health risks could not be calculated due to the lack of information on toxicological data. However, because Ti was the element with the highest concentrations in swimsuits, and taking into account the potential toxicity of TiO2 nanoparticles, further research is needed to assess the migration of this element from fibres to skin.

Risk assessment due to dermal exposure of trace elements and indigo dye in jeans: Migration to artificial sweat.

The concentration of a number of trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Cr, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were determined in 42 commercialized denim garments (jeans and shirts), being dermal exposure subsequently assessed. Migration experiments with artificial acid and basic sweat were also conducted to determine the release of these elements, as well as indigo dye. In a similar way than for the total content, Mg (124 and 99.4 µg/g) and Mn (27.1 and 7.20 µg/g) showed the highest concentrations in both artificial sweat, acid and basic, respectively. Indigo dye migrated at levels ranged from 3.22 to 7.76 mg/g, being higher in dark than in light blue fabrics. The levels of trace elements and indigo were analysed according to materials of fabric, colour, brand, and eco-labelling. Using total content and migrations rates, dermal exposure to trace elements for adult men, women and teenagers were calculated under the two sweat extractions. Non-carcinogenic and carcinogenic risks due to dermal exposure to the elements here analysed in cloths were assessed. Both risks were in the limits of safe to according to international regulations. However, the maximum exposure to Sb reached a hazard quotient (HQ) of 0.3 in clothes partially made of polyester. Despite some authors have established that indigo is an agonist of the aril receptor, health risks due to exposure to indigo dye were not calculated due the lack of toxicological data.

A Three-Year Emotional Intelligence Intervention to Reduce Adolescent Aggression: The Mediating Role of Unpleasant Affectivity.

Adolescents' aggressive behavior is a growing social problem with important implications for psychosocial adjustment. The teaching of emotional skills has an important impact on reducing aggression in schools. However, little scientific evidence has shown the explanatory mechanism through which this training reduces aggression during adolescence. This article aims to provide evidence for the effectiveness of a 3-year longitudinal intervention among adolescents in nine Spanish schools. A total of 476 adolescents participated. Results showed a reduction in physical and verbal aggression in Time 2 through the reduction in negative affect, anger, and hostile feelings, compared with an active control group. The training seems to be crucial for dealing with the emotional and cognitive components of aggression and, thus, their behavioral manifestations.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis.

BACKGROUND: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. METHODS: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). RESULTS: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). CONCLUSIONS: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study.

OBJECTIVE: The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients. METHODS: This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged ≥40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression. RESULTS: A total of 23 single nucleotide polymorphisms and the time of primary KOA diagnosis were significantly associated with KOA severe progression in the exploratory cohort (n = 220; P < 0.05). The predictive accuracy of the clinical variables was limited: area under the curve (AUC) = 0.66. When genetic variables were added to the clinical model (full model), the prediction of KOA progression was significantly improved (AUC = 0.82). Combining only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also obtained (AUC = 0.78). The predictive ability for KOA progression of the full model was confirmed on the replication cohort (two-sample Z-test; n = 62; P = 0.190). CONCLUSION: An accurate prognostic tool to predict primary KOA progression has been developed based on genetic and clinical information from OA patients.

Exercise Addiction and Intimate Partner Violence: The Role of Impulsivity, Self-Esteem, and Emotional Dependence.

Given the scarcity of studies linking exercise addiction to intimate partner violence, the present study aims to analyze the relationship between these variables and examine the potential mediating roles of emotional dependence, impulsivity, and self-esteem. This is a non-experimental, cross-sectional correlational design study. The sample comprised 887 university students (86% women, mean age 20.82 years, SD = 3.63). Elevated levels of exercise addiction were associated with increased impulsivity, emotional dependence, and exerted violence, as well as decreased self-esteem and perceived violence. Mediation models were tested, explaining 7% of the variance in received violence, 13% of the variance in exerted violence, and 6% of the variance in perceived violence. Higher levels of exercise addiction were linked to increased received and exerted violence and decreased perceived violence, attributed to the positive impact of exercise addiction on emotional dependence. This study highlights the mediating roles of self-esteem and impulsivity in the relationship between exercise addiction and partner violence. Identifying risk or vulnerability factors such as emotional dependence, impulsivity, and self-esteem related to exercise addiction and interpersonal partner violence is especially relevant for designing and implementing preventive interventions in the general young population.

Long-term effectiveness, safety, and tolerability of doravirine in antiretroviral-experienced people with HIV in real life.

Real-life data on doravirine (DOR) in different drug combinations are limited. We evaluated the effectiveness of DOR plus two nucleos(t)ide reverse transcriptase inhibitors (NRTI), mainly abacavir/lamivudine, and dual therapies in people with HIV (PWH), mostly virologically suppressed. Ambispective observational study that enrolled adults PWH who initiated a DOR-based regimen from September 2020 to February 2022 at a referral center in Spain. Participants were grouped as follows: A, received DOR plus two NRTI; B, dual therapy (DT) with DOR plus dolutegravir (DTG) or darunavir/cobicistat (DRVc); C, DOR plus ≥two antiretroviral drugs. The primary endpoints were treatment effectiveness at week 48 by intention-to-treat (ITT) and per-protocol analysis (OT). A cohort of 187 participants, 91% virologically suppressed, were analyzed after a median follow-up of 112 weeks (80-136). Group A received DOR plus abacavir/lamivudine (ABV/3TC) (n = 109) or tenofovir/emtricitabine (TFV/3TC) (n = 45). At week 48, the effectiveness of DOR plus ABV/3TC by ITT was 90.8% (CI95, 88.0-93.6), better than with TFV/FTC [73.3% (66.7-79.9); P = 0.003]. Only one virologic failure was observed. Mild adverse effects were the cause of treatment discontinuation in 7.8%, followed by switching to a single-tablet regimen. In group B, the effectiveness by ITT was 92.9% (CI95, 88.0-97.8) at week 48. No adverse effects or virologic failure were registered in this group. DOR plus two NRTI or DT have long-term effectiveness and safety as a switching option for PWH, mostly virologically suppressed. The DOR plus ABV/3TC combination has shown even better effectiveness than TFV/FTC.IMPORTANCEDOR-based regimens have shown long-term effectiveness and safety in PWH, mostly virologically suppressed. The combination of DOR plus ABV/3TC has shown even better safety and effectiveness than TFV/FTC. DOR plus two NRTI offers cost benefits compared to other regimens.

Trisomy 18p caused by a supernumerary marker with a chromosome 13/21 centromere: a possible recurrent chromosome aberration.

We present a clinical and molecular cytogenetic characterization of two new patients with a complex supernumerary marker consisting of the entire short arm of chromosome 18 with a chromosome 13/21 centromere. One patient is a girl with a nonsyndromic intellectual disability and the second is a prenatally diagnosed fetus. To our knowledge, these are the fourth and fifth such cases to be described in the literature, suggesting the existence of a possible recurring constitutional structural chromosome abnormality.