Measurement invariance of the Arizona Sexual Experience Scale by sexual orientation: comparing the sexual functioning of gay and heterosexual individuals.

BACKGROUND: The assessment of sexual functioning requires accurate and reliable measures as well as short and easy to apply. The Arizona Sexual Experience Scale (ASEX), which provides a quick, easy, and nonintrusive assessment of sexual functioning in men and women, is a clear example of a commonly used scale that satisfies these qualities. AIM: The study sought to examine measurement invariance and differential item functioning (DIF) by sexual orientation of the Spanish version of the ASEX. METHODS: A confirmatory factor analysis was performed on a sample of 1600 adults (800 gay and 800 heterosexual individuals), testing measurement invariance of the ASEX by sexual orientation in men and women separately, and calculating its reliability and DIF. OUTCOMES: The measure provided by the Spanish version of the ASEX is reliable and valid for assessing the sexual functioning of gay men and lesbians, but comparisons by sexual orientation are not recommended for men. RESULTS: The results of the confirmatory factor analysis confirmed the unidimensional structure of the ASEX already found in the Spanish validation with heterosexual people. Measurement invariance showed that, in the men's sample, the factor structure of the ASEX only reached the weak level of invariance, whereas in the women's sample, strict invariance by sexual orientation was reached. The internal consistency reliability was adequate, with better coefficients in women than in men. No significant DIF was observed in either men or women. CLINICAL IMPLICATIONS: Clinicians should further their training in sexual and gender diversity as approaches such as affirmative LGBT psychotherapy gain popularity, and they must have access to assessment instruments that are psychometrically robust enough to be used with this population. STRENGTHS AND LIMITATIONS: This research has some limitations. Because the distribution was administered solely through social media platforms, those without access to social media were unable to participate. Beyond these restrictions, however, the findings are thought to be significant from a research and clinical perspective since measurement invariance is a step that is often excluded when using an instrument validated in a mostly heterosexual sample. CONCLUSION: Validating assessment tools in gay men and lesbians is essential because sexual functioning is a crucial concept in sexual health. The findings of this study suggest that the Spanish version of the ASEX offers valid and reliable measures of sexual functioning for both heterosexual and gay people, though there would be bias in comparing men of both orientations.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Sleep, academic achievement, and cognitive performance in children with attention-deficit hyperactivity disorder: A polysomnographic study.

The objective of this study was to examine the influence of parent-reported and polysomnography (PSG)-measured sleep patterns on the academic and cognitive performance of children with attention-deficit hyperactivity disorder (ADHD). We assessed 91 children (18 girls) diagnosed with ADHD aged 7-11 years (29 ADHD-Inattentive, 32 ADHD-Hyperactive/Impulsive, and 31 ADHD-Combined). The Paediatric Sleep Questionnaire (PSQ) and Paediatric Daytime Sleepiness Scale (PDSS) were used to assess subjective sleep quality, as perceived by parents, and objective sleep variables were assessed by PSG. Cognitive performance was evaluated using the Wechsler Intelligence Scale for Children (WISC), and the final average grade of the last school year was used as a measure of academic performance. Academic performance was predicted by the following sleep variables: Sleep time, time in bed, night awakenings, and daytime sleepiness. The best predictors of cognitive performance in children with ADHD were rapid eye movement latency, light sleep, periodic limb movements index (PLMs), awakenings, and daytime sleepiness. In conclusion, sleep parameters are closely associated with the academic and cognitive functioning of children with ADHD.

Predicting condom use in adolescents: a test of three socio-cognitive models using a structural equation modeling approach.

BACKGROUND: The theory of planned behavior (TPB), socio-cognitive model (SCM), and information-motivation-behavioral skills (IMB) model are effective in predicting condom use. However, the adequacy of these three theoretical models in predicting the frequency of condom use (FCU) among young people has not been compared. This cross-sectional study tested the applicability and suitability of these three models in predicting the FCU, and analyzed the relationships among the postulated constructs. METHODS: Sexually experienced adolescents (n = 410) aged 13-18 completed a survey assessing the TPB, SCM, and IMB model constructs. Participants were students recruited from 18 high schools, randomly selected from the north, south, east, and southeast of Spain. A structural equation modelling (SEM) analysis was applied to test TPB, SCM and IBM and constructs relationships of each model using R. RESULTS: The results of SEM demonstrated that behavioral skills predict behavior via motivation as hypothesized by the IMB model, but not directly via knowledge about condom use and sexually transmitted infections (STIs). Cognitive factors, such knowledge about condom use and STIs as well as condom use self-efficacy, directly predicted the FCU when modeled as per the SCM. According to the TPB, condom use intention was the best predictor of the FCU, and condom use intention was predicted by attitudes toward condom use and subjective norms related to condom use, but perceived control was not directly or indirectly related to the FCU. Based on the data, the TPB becomes the best-fit model for predicting the FCU among young people compared to the SCM and IMB model. CONCLUSIONS: From a statistical perspective, the TPB seems to be the most suitable model for predicting the FCU among young people compared to the other models. Overall, key direct predictors of the FCU in adolescents included condom use intention, behavioral skills and cognitive factors, such as STIs knowledge and condom use self-efficacy. The next step should be to test integrative models that include personal, contextual, environmental, and social factors.

Association between personality traits and substance use in Spanish adolescents. / Asociación entre rasgos de personalidad y consumo de sustancias en adolescentes españoles.

Substance use is considered one of the most frequent risk behaviors during adolescence. Personality factors are linked to consumption during adolescence. Although there are studies on personality and consumption among Spanish adolescents, some outcomes are contradictory, and more studies including larger samples and using validated measures are needed. The aim of this study is to analyze the relationship between different personality factors and substance use among Spanish adolescents. Participants were 1,455 students aged between 13-18 years. The adaptation of the 16PF-IPIP Personality Inventory was applied to assess Warmth, Stability, Gregariousness, Friendliness, Sensitivity, Trust, Openness to experience, Sociability, Perfectionism, and Calmness. Participants were asked about their different consumption substances during their lifetime. Results provide evidence for a relationship between personality factors and psychoactive substance use. There are different distributions of alcohol use regarding personality traits. Furthermore, personality factors have some influence on consumption of alcohol, cannabis, and cocaine.Trust and Calmness influence average alcohol, cannabis, and cocaine consumption, whereas Sociability had no statistically significant influence on any of the three substances. The results from this study are highly useful in the design of preventive programs, as they provide more evidence of the role of personality traits as a risk factor.

El consumo de sustancias está considerado como una de las conductas de riesgo más frecuentes durante la adolescencia. Los factores de personalidad están relacionados con el consumo en la adolescencia.Aunque existen estudios sobre personalidad y consumo en adolescentes españoles, algunos resultados son contradictorios y son necesarios más estudios con muestras de mayor tamaño y que utilicen medidas validadas.El objetivo de este estudio es analizar la relación entre los diferentes factores de personalidad y el consumo de sustancias en adolescentes españoles. Participaron 1,455 estudiantes de secundaria entre 13 y 18 años. Se aplicó la adaptación del Inventario de Personalidad 16PFIPIP para evaluar Calidez, Estabilidad, Gregarismo, Amigabilidad, Sensibilidad, Confianza, Apertura, Sociabilidad, Perfeccionismo y Calma.Se preguntó a los participantes acerca de las diferentes sustancias que habían consumido a lo largo de su vida. Los resultados evidencian la relación entre las variables de personalidad y el consumo de sustancias psicoactivas. El consumo de alcohol presenta diferentes distribuciones con respecto a los rasgos de personalidad. Por otra parte, los factores de personalidad tienen cierta influencia en el consumo de alcohol, cannabis y cocaína. Confianza y Calma tienen influencia en el consumo de alcohol, cannabis y cocaína, mientras que Sociabilidad no presenta ninguna influencia estadísticamente significativa en ninguna de las tres sustancias.Los resultados de este estudio son de gran utilidad a la hora de diseñar programas preventivos, ya que proporcionan mayor evidencia sobre el papel de los rasgos de personalidad como factores de riesgo.

Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease.

Celia's Encephalopathy (MIM #615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers.

Sexual risk behaviors increasing among adolescents over time: comparison of two cohorts in Spain.

Despite advances in treatment and prevention, HIV/AIDS remains a serious health and social problem. This study's objective is to examine sexual behavior, levels of knowledge, and attitudes toward HIV/AIDS between two cohorts in Spanish adolescents, and to analyze gender differences in these cohorts. Participants were 2132 adolescents between 15 and 18 years of age: 1222 in 2006 (43.2% boys) and 910 in 2012 (54.1% boys). The results indicate lower HIV knowledge and less favorable attitudes about HIV/AIDS in the 2012 cohort. In addition, adolescents from the 2012 cohort had their first sexual intercourse at an earlier age and have more sexual partners than those from the 2006 cohort. Compared to boys, girls engage in fewer risky behaviors, although they did not use condoms with their stable partner; girls tended to use condom less when they were in a stable relationship than boys. This study confirms the insufficiency of prevention campaigns as well as the need to improve the impact from programs that promote healthy sexual habits. Assuming comparability of cohorts, this study suggests increased risk of HIV/AIDS over time.

A new seipin-associated neurodegenerative syndrome.

BACKGROUND: Seipin/BSCL2 mutations can cause type 2 congenital generalised lipodystrophy (BSCL) or dominant motor neurone diseases. Type 2 BSCL is frequently associated with some degree of intellectual impairment, but not to fatal neurodegeneration. In order to unveil the aetiology and pathogenetic mechanisms of a new neurodegenerative syndrome associated with a novel BSCL2 mutation, six children, four of them showing the BSCL features, were studied. METHODS: Mutational and splicing analyses of BSCL2 were performed. The brain of two of these children was examined postmortem. Relative expression of BSCL2 transcripts was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in different tissues of the index case and controls. Overexpressed mutated seipin in HeLa cells was analysed by immunofluorescence and western blotting. RESULTS: Two patients carried a novel homozygous c.985C>T mutation, which appeared in the other four patients in compound heterozygosity. Splicing analysis showed that the c.985C>T mutation causes an aberrant splicing site leading to skipping of exon 7. Expression of exon 7-skipping transcripts was very high with respect to that of the non-skipped transcripts in all the analysed tissues of the index case. Neuropathological studies showed severe neurone loss, astrogliosis and intranuclear ubiquitin(+) aggregates in neurones from multiple cortical regions and in the caudate nucleus. CONCLUSIONS: Our results suggest that exon 7 skipping in the BSCL2 gene due to the c.985C>T mutation is responsible for a novel early onset, fatal neurodegenerative syndrome involving cerebral cortex and basal ganglia.

[Validation of an HIV and other sexually transmitted infections knowledge scale in an adolescent population]. / Validación de una escala de conocimiento sobre el VIH y otras infecciones de transmisión sexual en población adolescente.

OBJECTIVE: The objective of this research is to determine the validity and reliability of a questionnaire designed to specifically assess the knowledge of HIV and other sexually transmitted infections in a Spanish adolescent population. DESIGN: Cross-sectional study for the validation of a questionnaire. LOCATION: A total of 17 schools in five Spanish provinces. PARTICIPANTS: A total of 1,570 adolescent schoolchildren between 13 and 17 years old. INTERVENTION: A pool of 40 items relating to knowledge about HIV and other sexually transmitted infections was established. This pool was analyzed by an expert panel. It was then administered to a pilot group with the same demographic characteristics of the sample, to ensure comprehension. MAIN MEASUREMENT: Item analysis, internal consistency, test/retest and exploratory factorial analysis. RESULTS: A factor analysis was performed, in which five factors that explained 46% of the total variance were retained: general knowledge about HIV, condom as a protective method, routes of HIV transmission, the prevention of HIV, and other sexually transmitted infections. Reliability measures ranged from 0.66 to 0.88. The test-retest correlation was 0.59. There were gender differences in the knowledge of infections. CONCLUSIONS: These factors have adequate internal consistency and acceptable test-retest correlation. Theoretically, these factors fit properly with the content of the items. The factors have a moderate relationship, indicating that a high degree of knowledge about an aspect, but not a guarantee of general knowledge. The availability of a questionnaire to assess knowledge of sexually transmitted infections is helpful to evaluate prevention programs.

Profound ctDNA and radiological responses after 2 cycles of avelumab in a metastatic Merkel cell carcinoma of the head and neck.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin cancer that in more than 90 % of cases develops within the head and neck region. MCC is an aggressive disease with a dismal prognosis before the advent of immunotherapy. Avelumab, an anti-PDL1 agent is approved since 2017 for the treatment of advanced MCC after demonstrating a high response rate and favorable impact in survival. METHODS: Next generation sequencing (NGS) of the primary tumor biopsy from initial diagnosis (Foundation One CDx, Roche Diagnostics) as well as from plasma samples (Foundation One Liquid, Roche Diagnostics) obtained before and during treatment with avelumab were performed. RESULTS: We present the case of a patient with a metastatic MCC developing in the left parotid gland / pre-auricular area in an 80-year-old male with a long-lasting history of high UV exposure. After two cycles of avelumab 10 mg/kg/q2wk a near complete metabolic response and a major radiological response occurred in parallel to a brisk reduction in the ctDNA tumor fraction as well as variant-allele frequencies (VAFs) of all the mutations detected before the start of avelumab. CONCLUSION: Avelumab may achieve rapid and major responses in metastatic MCC. Our study demonstrates that ctDNA mirrors radiological responses and may serve as an ideal companion for diagnosis and disease monitoring in MCC.

Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.

Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.

Sleep Patterns during the COVID-19 Lockdown in Spain.

BACKGROUND: To mitigate the spread of the coronavirus disease (COVID-19) pandemic, governments around the world adopted exceptional lockdown measures. This led to the disruption of normal life routines, including sleep. The aim of this study was to analyze differences in sleep patterns and subjective variables of sleep quality before and during lockdown. METHODS: A sample of 1673 Spanish adults (30% men; 82% of the total were between 21 and 50 years of age) was evaluated. The following sleep variables were evaluated: Sleep latency, sleep time, number and duration of awakenings, sleep satisfaction, daytime sleepiness, and the manifestation of symptoms related to sleep problems. RESULTS: Although 45% of people changed their sleep schedules (resulting in 42% sleeping longer during lockdown), sleep quality (37.6% worse), daytime sleepiness (28% worse), number of awakenings (36.9% more), and duration of awakenings (45% longer) were markedly worse. Statistical analyses indicated significant differences in all the evaluated sleep variables before and during lockdown in both men and women. Women reported less sleep satisfaction, and more symptoms related to sleep problems than men. CONCLUSIONS: A deterioration in the sleep patterns of the Spanish population, especially women, because of the lockdown declared due to the COVID-19 pandemic.

Measurement Invariance across Sexual Orientation for Measures of Sexual Attitudes.

Despite the growing interest in the study of sexual attitudes across sexual orientation, few studies have tested whether the instruments used to measure them are invariant. This study examined measurement invariance (configural, weak, strong, and strict) across sexual orientation in three different sexual attitude scales: the Sexual Opinion Survey (SOS) to assess erotophilia, the Hurlbert Index of Sexual Fantasy (HISF) to assess attitudes toward sexual fantasies, and the Negative Attitudes Toward Masturbation Inventory (NATMI) to assess negative attitudes toward masturbation. A total of 2293 Spanish adult men and women with different sexual orientations (i.e., heterosexual, bisexual, and gay) participated in the study. The results indicated strict invariance for HISF across sexual orientation and only weak invariance for SOS and NATMI. Differential item functioning was also found in two items of the NATMI scale. Evidence of validity was provided for the three scales that were studied.

Congestive heart failure in a 77-year-old woman receiving adjuvant treatment with imatinib for a large gastric gastrointestinal stromal tumour.

We report on a 77-year-old patient complaining of abdominal pain who was diagnosed with a gastric mesenchymal tumour with a poor prognosis (high mitotic index, 25% Ki-67 proliferation index and c-kit positive). During surgery, there was instrument-related rupture of the tumour. Coadjuvant therapy with imatinib was initiated. Three weeks later, the patient developed symptoms of congestive heart failure and this led to the discontinuation of imatinib treatment; diuretic treatment was initiated, which led to an improvement in the symptoms. Echocardiography study showed a left ventricle ejection fraction of 55% with an alteration in the relaxation of the ventricle. In the follow-up, there has been no evidence of disease relapse or development of new symptoms.

Content Validity through Expert Judgment for the Depression Clinical Evaluation Test.

Background/Objective: The evaluation of depression requires valid and reliable measuring instruments, which collect a wide spectrum of symptoms that this disorder displays, in order to carry out an accurate and differential diagnosis. The objective of this work is the construction of the Depression Clinical Evaluation Test (DCET), where affective, somatic, cognitive, behavioral and interpersonal symptoms are considered and also analyze its content validity through an expert judgment. Method: Based on different diagnostic and manual classifications, a specification table for a depression test was established. In its evaluation, 16 experts in Psychological Assessment, Psychometry and/or Psychopathology participated. A total of 300 items were created. The experts had to assess the items according to the criteria of Content, Relevance, Clarity, Comprehension, Sensitivity, and Offensiveness. In addition, 50 adults, evaluated the compression of the items. Results: The degree of understanding for all the items was high and the expert judgment favoured the suppression of 104 items, thus obtaining a shorter measuring instrument with a total of 196 items for ease of application. Conclusions: The content validity of the test is adequate and fits the agreed definition of depression.

Antecedentes: La evaluación de la depresión requiere de instrumentos de medida válidos, fiables y que recojan el amplio espectro de síntomas que este trastorno conlleva, para poder llevar a cabo un diagnóstico certero y diferencial. El objetivo de este trabajo es la construcción del Test de Evaluación Clínica de la Depresión (TECD), que contempla síntomas afectivos, somáticos, cognitivos, conductuales e interpersonales, y analizar su validez de contenido a través de un juicio de expertos. Método: A partir de diferentes clasificaciones diagnósticas y manuales se estableció la tabla de especificación del test para este cuestionario de depresión. En la evaluación de este participaron 16 expertos en Evaluación Psicológica, Psicometría y/o Psicopatología. Se crearon 300 ítems en total, que los expertos tuvieron que valorar atendiendo a los criterios de Contenido, Relevancia, Claridad, Comprensión, Sensitividad y Ofensividad. Además, 50 adultos, valoraron la compresión de los items. Resultados: El grado de comprensión de todos los ítems fue elevado y el juicio de expertos supuso la supresión de 104 ítems, obteniendo así un instrumento de medida más breve, con 196 ítems en total, lo que facilitará su aplicación. Conclusiones: La validez de contenido del test es adecuada y se adapta a la definición de depresión establecida.

Network and Exploratory Factorial Analysis of the Depression Clinical Evaluation Test.

Depression is a highly prevalent disorder with a wide range of symptomatology. Existing instruments for its assessment have only a few items for each factor. The Depression Clinical Evaluation Test (DCET) has been created to cover all depression symptoms at different times (month, year, and always) with several items for each facet. The content validity of this instrument has been judged by experts and, in this paper, we analyse its factorial structure and make a network analysis of it. The test (196 items) was administered to 602 adults without psychological disorders (Mage = 24.7, SD = 8.38, 72% women) both online and on paper. A network was estimated for each time point, using the absolute minimum selection and shrinkage operator. From the factor analysis, 12 factors were established for month, 11 for year, and 10 for always, leaving 94 items. The network analysis showed that the facets of depressive mood, anhedonia, and thoughts of Death, are central to all the estimated networks. The DCET is proposed as a valid and reliable multifactorial instrument to detect the variability of depressive symptoms in adults, guaranteeing its diagnostic usefulness.

Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial.

Importance: Obesity is the leading cause of obstructive sleep apnea (OSA); however, the effects of weight loss and lifestyle interventions on OSA and comorbidities remain uncertain. Objective: To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on OSA and comorbidities among adults with moderate to severe OSA and overweight or obesity. Design, Setting, and Participants: The Interdisciplinary Weight Loss and Lifestyle Intervention for OSA (INTERAPNEA) study was a parallel-group open-label randomized clinical trial conducted at a hospital-based referral center in Granada, Spain, from April 1, 2019, to October 23, 2020. The study enrolled 89 Spanish men aged 18 to 65 years with moderate to severe OSA and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater who were receiving continuous positive airway pressure (CPAP) therapy. The sole inclusion of men was based on the higher incidence and prevalence of OSA in this population, the differences in OSA phenotypes between men and women, and the known effectiveness of weight loss interventions among men vs women. Interventions: Participants were randomized to receive usual care (CPAP therapy) or an 8-week weight loss and lifestyle intervention involving nutritional behavior change, aerobic exercise, sleep hygiene, and alcohol and tobacco cessation combined with usual care. Main Outcomes and Measures: The primary end point was the change in the apnea-hypopnea index (AHI) from baseline to the intervention end point (8 weeks) and 6 months after intervention. Secondary end points comprised changes in other OSA sleep-related outcomes, body weight and composition, cardiometabolic risk, and health-related quality of life. Results: Among 89 men (mean [SD] age, 54.1 [8.0] years; all of Spanish ethnicity; mean [SD] AHI, 41.3 [22.2] events/h), 49 were randomized to the control group and 40 were randomized to the intervention group. The intervention group had a greater decrease in AHI (51% reduction; change, -21.2 events/h; 95% CI, -25.4 to -16.9 events/h) than the control group (change, 2.5 events/h; 95% CI, -2.0 to 6.9 events/h) at the intervention end point, with a mean between-group difference of -23.6 events/h (95% CI, -28.7 to -18.5 events/h). At 6 months after intervention, the reduction in AHI was 57% in the intervention group, with a mean between-group difference of -23.8 events/h (95% CI, -28.3 to -19.3 events/h). In the intervention group, 18 of 40 participants (45.0%) no longer required CPAP therapy at the intervention end point, and 6 of 40 participants (15.0%) attained complete OSA remission. At 6 months after intervention, 21 of 34 participants (61.8%) no longer required CPAP therapy, and complete remission of OSA was attained by 10 of 34 participants (29.4%). In the intervention vs control group, greater improvements in body weight (change, -7.1 kg [95% CI, -8.6 to -5.5 kg] vs -0.3 kg [95% CI, -1.9 to 1.4 kg]) and composition (eg, change in fat mass, -2.9 kg [95% CI, -4.5 to -1.3 kg] vs 1.4 kg [95% CI, -0.3 to 3.1 kg]), cardiometabolic risk (eg, change in blood pressure, -6.5 mm Hg [95% CI, -10.3 to -2.6 mm Hg] vs 2.2 mm Hg [95% CI, -2.1 to 6.6 mm Hg]), and health-related quality of life (eg, change in Sleep Apnea Quality of Life Index, 0.8 points [95% CI, 0.5-1.1 points] vs 0.1 points [95% CI, -0.3 to 0.4 points]) were also found at the intervention end point. Conclusions and Relevance: In this study, an interdisciplinary weight loss and lifestyle intervention involving Spanish men with moderate to severe OSA and had overweight or obesity and were receiving CPAP therapy resulted in clinically meaningful and sustainable improvements in OSA severity and comorbidities as well as health-related quality of life. This approach may therefore be considered as a central strategy to address the substantial impact of this increasingly common sleep-disordered breathing condition. Trial Registration: ClinicalTrials.gov Identifier: NCT03851653.

Immunotherapy in microsatellite instability metastatic colorectal cancer: Current status and future perspectives.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. This specific pathology is composed of various molecular entities, with distinct immunological phenotypes. In addition to KRAS, NRAS, and BRAF mutation status, other druggable alterations such as those in HER2, MET, NTRK, ALK, and ROS1 have been identified in recent years offering new therapeutic options for some patients with CRC. AIM: This review will focus on the molecular biology, immunological fingerprints, and current clinical evidence for the use of immunotherapy in patients with CRC. RELEVANCE FOR PATIENTS: High microsatellite instability (MSI-H) and mutations in mismatch repair genes constitute a new molecular entity within CRC, which is characterized by a high mutational and neoantigen burden, frequent immune cell infiltration, and where immune checkpoint inhibitors have shown high response and survival rates compared to microsatellite stable (MSS) tumors. Indeed, the approval of pembrolizumab in MSI-H tumors was the first agnostic FDA approval in solid tumors. While monotherapy with anti-programmed cell death protein-1 agents achieves objective response rates (ORR) of around 30% and 1-year overall survival (OS) rates of 76%, anti-PD1, and anti-CTLA4 combinations achieve a 55% ORR and a 1-year OS rate of 85%. Several ongoing trials are evaluating the use of different immunotherapy combinations, both in the advanced and early settings and in MSI-h and MSS CRCs.

Personalizing first-line treatment in advanced colorectal cancer: Present status and future perspectives.

BACKGROUND: Colorectal cancer is one of the most frequent neoplasms worldwide, and the majority of patients are diagnosed in advanced stages. Metastatic colorectal cancer (mCRC) harbors several mutations with different prognostic and predictive values; KRAS, NRAS, and BRAF mutations are the best known. Indeed, RAS and BRAF molecular status are associated with a different response to monoclonal antibodies (Anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor agents), which are usually added to chemotherapy in first-line, and thus allow to select the optimal therapy for patients with mCRC. Furthermore, sidedness is an important predictive and prognostic factor in mCRC, which is explained by the different molecular profile of left and right-sided tumors. Recently, microsatellite instability-high has emerged as a predictive factor of response and survival from immune checkpoint inhibitors in mCRC. Finally, several other alterations have been described in lower frequencies, such as human epidermal growth factor receptor-2 overexpression/amplification, PIK3CA pathway alterations, phosphatase and tension homolog loss, and hepatocyte growth factor/mesenchymal-epithelial transition factor pathway dysregulation, with several targeted therapies already demonstrating activity or being tested in currently ongoing clinical trials. AIM: To review the importance of studying the predictive and prognostic roles of the molecular profile of mCRC, the changes occurred in recent years and how they would potentially change in the near future, to guide physicians in treatment decisions. RELEVANCE FOR PATIENTS: Today, several different therapeutic options can be offered to patients in the first-line setting of mCRC. Therapies at present approved or under investigation in clinical trials will be thoroughly reviewed, with special emphasis on the molecular rationale behind them. Understanding the molecular status, resistance mechanisms and potential new druggable targets may allow physicians to choose the best therapeutic option in the first-line mCRC.

Characteristics of sleep spindles in school-aged children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a complex disorder, characterized by different presentations with distinct cognitive and neurobiological characterizations. Here we aimed to investigate whether sleep spindle activity, which has been associated with brain maturation, may be a potential biomarker able to differentiate ADHD presentations in school-aged children (7-11 years). METHOD: Spindle characteristics were extracted from overnight polysomnography in 74 children (27 ADHD-Inattentive [IQ = 96.04], 25 ADHD-hyperactive/impulsive [IQ = 98.9], and 22 ADHD-combined [IQ = 96.1]). We obtained data of the frontal (Fz) and parietal (Pz) derivations using a validated spindle detection algorithm. RESULTS: Children with ADHD showed a higher number and density of slow compared to fast spindles which were more frequent in frontal area. No differences were observed among ADHD presentations for any spindle characteristics. Spindle frequency and density increased with age, indicating an age-dependent maturation of different sleep spindles. However, no associations between IQ and spindle characteristics were observed. CONCLUSIONS: In children with ADHD the spindle characteristics evolve with age but sleep spindle activity does not seem to be a valid biomarker of ADHD phenotypes or general cognitive ability.