Association between mediterranean diet and metal(loid) exposure in 4-5-year-old children living in Spain.

Even relatively low levels of metals exposure may impact health, particularly among vulnerable populations such as infants and young children. However, little is known about the interplay between simultaneous metal exposures, common in real-life scenarios, and their association with specific dietary patterns. In this study, we have evaluated the association between adherence to Mediterranean diet (MD) and urinary metal concentrations individually and as an exposure mixture in 713 children aged 4-5-years from the INMA cohort study. We used a validated food frequency questionnaire to calculate two MD indexes scores: aMED and rMED. These indexes gather information on various food groups within the MD and score differently. To measure urinary concentrations of cobalt, copper, zinc, molybdenum, selenium, lead, and cadmium as exposure biomarkers, we used inductively coupled plasma mass spectrometry (ICP-MS), coupled with an ion chromatography (IC) equipment for arsenic speciation analysis. We applied linear regression and quantile g-computation, adjusted for confounders, to analyse the association between MD adherence and exposure to the metal mixture. High adherence to MD such as the quintile (Q) 5 MD was associated with higher urinary arsenobetaine (AsB) levels than Q1, with ß values of 0.55 (confidence interval - CI 95% 0.01; 1.09) for aMED and 0.73 (CI 95% 0.13; 1.33) for rMED. Consumption of fish was associated with increased urinary AsB but reduced inorganic arsenic concentrations. In contrast, the aMED vegetables consumption increased urinary inorganic arsenic content. A moderate level of adherence to MD (Q2 and Q3) was associated with lower copper urinary concentrations than Q1, with ß values of -0.42 (CI 95% -0.72; -0.11) for Q2 and -0.33 (CI 95% -0.63; -0.02) for Q3, but only with aMED. Our study, conducted in Spain, revealed that adhering to the MD reduces exposure to certain metals while increasing exposure to others. Specifically, we observed increase in exposure to non-toxic AsB, highlighting the significance of consuming fish/seafood. However, it is crucial to emphasize the necessity for additional efforts in reducing early-life exposure to toxic metals, even when adhering to certain food components of the MD.

The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Effects of tetracycline, sulfonamide, fluoroquinolone, and lincosamide load in pig slurry on lettuce: Agricultural and human health implications.

The application of pig slurry as fertilizer in agriculture provides nutrients, but it can also contain veterinary medicines, including antibiotic residues (ABs), which can have an ecotoxicological impact on agroecosystems. Furthermore, uptake, translocation, and accumulation of ABs in crops can mobilize them throughout the food chain. This greenhouse study aims to assess AB uptake from soil fertilized with pig slurry and its phenotypical effects on Lactuca sativa L. The plants were cropped in loamy clay soil dosed at 140 kg total N/ha and containing antibiotics (lincomycin, sulfadiazine, oxytetracycline, and enrofloxacin) at different concentration levels (0, 0.05, 0.5, 5, 50, and 500 mg/kg fresh weight, fw). Whereas sulfadiazine (11.8 ng/g fw) was detected in lettuce leaves at the intermediate doses (0.5 mg/kg), lincomycin and its transformation products (hydroxy/sulfate) were only detected at the 50 mg/kg fw dose. In addition, increased AB doses in the pig slurry resulted in decreased lettuce fresh weight and lipid and carbohydrate content and became lethal to lettuce at the highest AB concentrations (500 mg/kg fw). Nevertheless, even at higher doses, the AB content in lettuce following pig-slurry fertilization did not pose any direct significant human health risk (total hazard quotient<0.01). However, the promotion of antimicrobial resistance in humans due to the intake of these vegetables cannot be ruled out.

Long-term outcomes and quality of life assessment after posterior component separation with transversus abdominis muscle release (TAR).

BACKGROUND: Although transversus abdominis release (TAR) to treat large incisional hernias has shown favorable postoperative outcomes, devastating complications may occur when it is used in suboptimal conditions. We aimed to evaluate postoperative outcomes and long-term follow-up after TAR for large incisional hernias. METHODS: A consecutive series of patients undergoing TAR for complex incisional hernias between 2014 and 2019 with a minimum of 6 month follow-up was included. Demographics, operative and postoperative variables were analyzed. Postoperative imaging (CT-scan) was also evaluated to detect occult recurrences. The HerQLes survey for quality of life (QoL) assessment was performed preoperatively and 6 months after the surgery. RESULTS: A total of 50 TAR repairs were performed. Mean age was 65 (35-83) years, BMI was 28.5 ± 3.4 kg/m2, and 8 (16%) patients had diabetes. Mean Tanaka index was 14.2 ± 8.5. Mean defect area was 420 (100-720) cm2, average defect width was 19 ± 6.2 cm, and mesh area was 900 (500-1050) cm2; 78% were clean procedures, and in 60% a panniculectomy was associated. Operative time was 252 (162-438) minutes, and hospital stay was 4.5 (2-16) days. Thirty-day morbidity was 24% (12 patients), and 16% (8 patients) had surgical site infections. Overall recurrence rate was 4% (2 patients) after 28.2 ± 20.1 months of follow-up. QoL showed a significant improvement after surgery (p = 0.001). CONCLUSIONS: The TAR technique is an effective treatment modality for large incisional hernias, showing an acceptable postoperative morbidity, a significant improvement in QoL, and low recurrence rates at long-term follow-up.

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL.

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.

Comparison of cell invasion, macrophage survival and inflammatory cytokines profiles between Salmonella enterica serovars Enteritidis and Dublin from Brazil.

AIMS: This study compared the capacity of strains of Salmonella enterica serovars Enteritidis and Dublin isolated in Brazil to invade epithelial cells, to be internalized by and survive within macrophages, and to stimulate cytokine release in vitro. METHODS AND RESULTS: Both serovars infected 75 and 73% Caco-2 (human) and MDBK (bovine) epithelial cells respectively. Salmonella Dublin and S. Enteritidis (i) were internalized at the respective rates of 79·6 and 65·0% (P ≤ 0·05) by U937 (human) macrophages, and 70·4 and 66·9% by HD11 (chicken) macrophages; and (ii) multiplied at the respective rates of 3·2- and 2·7-fold within U937 cells, and 1·9- and 1·1-fold (P ≤ 0·05) within HD11 cells respectively. Seventy per cent of 10 S. Dublin strains stimulated IL-8 production, while 70% of S. Enteritidis strains enhanced production of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF in Caco-2 cells. CONCLUSIONS: Compared with S. Enteritidis, S. Dublin had stronger ability to survive within macrophages and induced weak cytokine production, which may explain the higher incidence of invasive diseases caused by S. Dublin in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study compared S. enterica serovars Enteritidis and Dublin to provide comparative data about the profile of the two serovars in cells from humans, the common host and their respective natural animal hosts and vice versa in order to check the differences between these two phylogenetically closely related serovars that share antigenic properties but present different phenotypic behaviours.

Evaluation of Dysphagia in Motor Neuron Disease. Review of Available Diagnostic Tools and New Perspectives.

Oropharyngeal dysphagia (OD) is highly prevalent (up to 80%) in patients with motor neuron disease (MND), influencing the prognosis of the disease. The clinical assessment of dysphagia is complex. There are assessment scales and screening questionnaires, but they have not been tested in patients with MND. In a sample of 46 patients with MND, the sensitivity and specificity of the EAT-10 and SwalQoL questionnaires, as well as the ALS-SS and FOIS scales, were tested and compared to the gold standard technique (videofluoroscopy, VFS). The patients were stratified using the DOSSc variable according to the video fluoroscopic examination with (n = 37) or without (n = 8) signs of dysphagia, and the results were compared with the scores obtained in the dysphagia questionnaires. None of the studied questionnaires was more sensitive than the others, but one stood out for its high specificity (= 1): the SwalQoL revised FS. The symptom frequency section of the SwalQoL questionnaire with some modifications, (SwalQoL revised FS) may be a useful tool in the clinical assessment of dysphagia because it's capable to detect the patients that really don't have dysphagia. The ALS-SS showed the greatest validity as a severity scale of dysphagia among the sample studied. A specific questionnaire for screening for dysphagia in MND needs to be developed. Until that time, the proposal is to use a combination of the existing questionnaires for other pathologies (EAT-10 and SwalQoL) and the specific scale for MND, the ALS-SS, to make an accurately clinical assessment of OD in MND patients before to perform a videofluoroscopy.

Differential risk for COVID-19 in the first wave of the disease among Spaniards and migrants from different areas of the world living in Spain. / Riesgo de COVID-19 en españoles y migrantes de distintas zonas del mundo residentes en España en la primera oleada de la enfermedad.

INTRODUCTION AND OBJECTIVES: Little is known regarding the relevance of racial/ethnic background to the risk for COVID-19 infection, particularly in Europe. We evaluated the risk of COVID-19 among migrants from different areas of the world within the context of universal free access to medical care. MATERIAL AND METHODS: We conducted a population-based cohort analysis of the cumulative incidence of PCR-confirmed COVID-19 among adult residents of Alcorcon (Spain) in the first wave of the disease up to April 25, 2020. RESULTS: The crude cumulative incidence among migrants (n=20,419) was higher than among Spaniards (n=131,599): 8.81 and 6.51 and per 1,000 inhabitants, respectively (p<.001), but differed by region of origin. As per a negative binomial regression adjusted for age and sex, relative risk (RR) for COVID-19 for individuals from Europe, Asia, or North Africa was not significantly different from Spaniards. In contrast, a markedly increased risk was found for people from Sub-Saharan Africa (RR 3.66, 95% confidence interval (CI) 1.42-9.41, p=.007), the Caribbean (RR 6.35, 95% CI 3.83-10.55, p<.001), and Latin America (RR 6.92, 95% CI 4.49-10.67, p<.001). CONCLUSIONS: Migrants from Sub-Saharan Africa, the Caribbean, and Latin America exhibited increased risk for COVID-19 as compared to Spaniards or migrants from Europe, North Africa, or Asia. Our data suggest that the ethnic background may play a role in risk for COVID-19. Migrants from some areas of the world may merit closer attention for both clinical and epidemiological reasons.

Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder.

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

Psychopathology and traffic violations in subjects who have lost their driving license.

BACKGROUND: The persistence of risky behaviors while driving and traffic accidents despite campaigns to increase awareness suggest that there may be underlying causes that maintain proneness to traffic violations. The aim of the current study was to assess: a) the prevalence of psychopathology in a sample of people who have lost their driving license due to former traffic violations and b) the discriminatory capacity of each psychopathological disorder to differentiate among people with high and low proneness to perform risky behaviors while driving. METHODS: 383 participants in a course to recover their driving license after its loss due to previous traffic violations were included. The International Neuropsychiatric Interview (M.I.N.I.) according to DSM-IV was used to assess psychopathology. RESULTS: Between 67% and 76.2% of the participants had been affected by a lifetime psychopathological disorder until the moment of assessment. The most prevalent diagnoses were substance abuse including alcohol (52.5-62.7%), ADHD (19.7-28.5%), depression (7.9-14.4%) and anxiety (3.6-12.4%). Substance abuse and ADHD also showed the strongest set of associations with specific risk behaviors, but ADHD emerged as the most discriminant disorder to distinguish between those people at high and low risk of while driving. CONCLUSIONS: The results of the current study suggest that addressing psychopathology explicitly to prevent risky behaviors and recidivism while driving would provide benefits in this area.

Ultrafine particles and black carbon personal exposures in asthmatic and non-asthmatic children at school age.

Traffic-related air pollution (TRAP) exposure during childhood is associated with asthma; however, the contribution of the different TRAP pollutants in each microenvironment (home, school, transportation, others) in asthmatic and non-asthmatic children is unknown. Daily (24-h) personal black carbon (BC), ultrafine particle (UFP), and alveolar lung-deposited surface area (LDSA) individual exposure measurements were obtained from 100 children (29 past and 21 current asthmatics, 50 non-asthmatics) aged 9±0.7 years from the INMA-Sabadell cohort (Catalonia, Spain). Time spent in each microenvironment was derived by the geolocation provided by the smartphone and a new spatiotemporal map-matching algorithm. Asthmatics and non-asthmatics spent the same amount of time at home (60% and 61%, respectively), at school (20% and 23%), on transportation (8% and 7%), and in other microenvironments (7% and 5%). The highest concentrations of all TRAPs were attributed to transportation. No differences in TRAP concentrations were found overall or by type of microenvironment between asthmatics and non-asthmatics, nor when considering past and current asthmatics, separately. In conclusion, asthmatic and non-asthmatic children had a similar time-activity pattern and similar average exposures to BC, UFP, and LDSA concentrations. This suggests that interventions should be tailored to general population, rather than to subgroups defined by disease.

[Clinical and psychopathological factors associated with impulse control disorders in Parkinson's disease]. / Factores clínicos y psicopatológicos asociados a los trastornos del control de impulsos en la enfermedad de Parkinson.

INTRODUCTION: Impulse control disorders (ICD) constitute a complication that may arise during the course of Parkinson's disease (PD). Several factors have been linked to the development of these disorders, and their associated severe functional impairment requires specific and multidisciplinary management. The objective of this study was to evaluate the frequency of ICDs and the clinical and psychopathological factors associated with the appearance of these disorders. METHODS: Cross-sectional, descriptive, and analytical study of a sample of 115 PD patients evaluated to determine the presence of an ICD. Clinical scales were administered to assess disease severity, personality traits, and presence of psychiatric symptoms at the time of evaluation. RESULTS: Of the 115 patients with PD, 27 (23.48%) displayed some form of ICD; hypersexuality, exhibited by 14 (12.2%), and binge eating, present in 12 (10.1%), were the most common types. Clinical factors associated with ICD were treatment with dopamine agonists (OR: 13.39), earlier age at disease onset (OR: 0.92), and higher score on the UPDRS-I subscale; psychopathological factors with a significant association were trait anxiety (OR: 1.05) and impulsivity (OR: 1.13). CONCLUSIONS: ICDs are frequent in PD, and treatment with dopamine agonists is the most important risk factor for these disorders. High impulsivity and anxiety levels at time of evaluation, and younger age at disease onset, were also linked to increased risk. However, presence of these personality traits prior to evaluation did not increase risk of ICD.

Complementary role of magnetic resonance imaging in the study of the fetal urinary system.

Urinary system birth defects represent the abnormality most often detected in prenatal studies, accounting for 30% to 50% of all structural anomalies present at birth. The most common disorders are urinary tract dilation, developmental variants, cystic kidney diseases, kidney tumors, and bladder defects. These anomalies can present in isolation or in association with various syndromes. They are normally evaluated with sonography, and the use of magnetic resonance imaging (MRI) is considered only in inconclusive cases. In this article, we show the potential of fetal MRI as a technique to complement sonography in the study of fetal urinary system anomalies. We show the additional information that MRI can provide in each entity, especially in the evaluation of kidney function through diffusion-weighted sequences.

Bipolar disorder with comorbid attention-deficit and hyperactivity disorder. Main clinical features and clues for an accurate diagnosis.

OBJECTIVE: To study the prevalence of attention-deficit and hyperactivity disorder (ADHD) in adult patients with bipolar disorder (BD) and identify differential clinical features for a better diagnosis. METHOD: A total of 163 euthymic bipolar out-patients were screened for ADHD with the ASRS.V1 and the WURS at a BD Unit. Patients with a positive screening were assessed with the CAADID, at an ADHD unit. Sociodemographic and clinical features of the groups with and without ADHD were compared. RESULTS: Lifetime prevalence of comorbid ADHD was 17.9% (10.5% for adult ADHD and 7.4% for childhood ADHD). The BD + ADHD group showed more suicidal behaviour although less severe. Comorbidity was also more common, especially regarding substance use disorders. Nevertheless, these patients did not show more affective episodes or hospitalizations and suffered more atypical but less melancholic depression. However, they required more treatment with psychotherapy and valproate. One-third of positive screenings at the ASRS were false; a severe course of BD was the hallmark of this subgroup. CONCLUSION: Adult patients with BD and ADHD show differential clinical features, but not a more severe course of BD. Comorbidity with substance abuse is a big issue, deserving special clinical attention. Better screening tools are necessary to avoid overdiagnosis of comorbid ADHD in BD.

Psychiatrists admitted to a physicians' health programme.

BACKGROUND: Psychiatrists are at a high risk of becoming mentally ill at some point during their careers. AIMS: To compare the profile of psychiatrists admitted to the Barcelona Physicians' Health Programme (PHP) with other sick doctors in the programme. METHODS: A retrospective case review of electronic medical records was conducted for physicians registered at the 'Colegio de Médicos' in Barcelona and consecutively admitted to the Barcelona PHP from January 1998 until December 2013. RESULTS: One thousand two hundred eighteen records were reviewed. The 72 psychiatrists admitted to the programme were not statistically different from the other physicians in gender (54% versus 51% women), primary diagnosis (34% non-substance use mental disorders versus 29% substance use disorders), prevalence of adjustment disorders and median length of their first treatment episode (9.0 versus 8.4 months). Psychiatrists were significantly older (mean age 53 versus 50 years; t = 2.12; P < 0.05), more frequently had inpatient treatment during their first treatment episode (17% versus 10%; χ (2) = 4.57, P < 0.05) and had more referred (rather than self-referred) admissions (22% versus 13%; χ (2) = 4.57, P < 0.05) than other physicians. However, only the type of referral played a significant role when considering the simultaneous effect of all relevant variables (Wald = 4.43; P < 0.05). CONCLUSIONS: Psychiatrists with mental disorders may be more reluctant to ask for help from a PHP voluntarily than other physicians. Members of this professional group should be encouraged to seek help when affected by mental distress or addiction problems.

Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial.

BACKGROUND: There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. METHODS: 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. RESULTS: The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d' = 0.55). CONCLUSIONS: The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered.

Physicochemical stability of a new topical timolol 0.5% gel formulation for the treatment of infant hemangioma.

Infant hemangioma (IH) is the most common tumor in infants, which affects 5-10% of white children. It is a tumor of vascular origin that appears in the first months of life. The indication for the treatment of the IH is not approved in the datasheet of the product, however it has been used in the infant hemangioma by topical administration as an alternative to oral propranolol, avoiding the main problems of the oral route (bradycardia and hypotension). The objective of this work is to study the physical and chemical (HPLC stability indicating method) stability of a 0.5% timolol gel for topical application during 60 days (considering the stability limit as 90% of initial concentration of timolol maleate). The gel was prepared with a polyacrylic acid derivative and the physical stability of the system was studied by visual control, rheological and mechanical characterization. The studied formulation guarantees the correct dose administering and stability after 60 days stored at 25 ± 2 °C and light protected (tube of aluminum). We have developed an easy topical gel for the treatment of infant hemangioma with physical and chemical stability higher than those provided by the majority of hospitals.

Early-age clinical and developmental features associated to Substance Use Disorders in Attention-Deficit/Hyperactivity Disorder in Adults.

OBJECTIVE: The main objective was to explore early-age conditions associated to Substance Use Disorders (SUD) in adults with Attention Deficit/Hyperactivity Disorder (ADHD); secondly, to determine which of those conditions are specific to ADHD subjects; and finally, to compare ADHD and non-ADHD subjects in terms of SUD lifetime prevalence and professional, social and personal adjustment. METHOD: Comparison between ADHD adults with (n=236) and without lifetime SUD (n=309) regarding clinical characteristics of ADHD, externalization disorders, temperamental traits, environmental factors, academic history and family psychiatric history; secondly, ADHD subjects were compared to a non-ADHD group (n=177) concerning those variables. RESULTS: The following variables were found to be positively associated to SUD in ADHD subjects: ADHD severity, CD and ODD comorbidities, temperamental characteristics ("fearful", "accident prone" and "frequent temper tantrums"), "sexual abuse", "be suspended from school", family history of SUD and ADHD, and male gender; ADHD inattentive subtype and "fearful" were inversely associated to SUD. From those variables, "frequent temper tantrums" was also associated to SUD in non-ADHD subjects. ADHD subjects had higher prevalence of lifetime SUD and greater professional, social and personal impairment than non-ADHD subjects. CONCLUSION: Findings suggest a significant association between ADHD, SUD and early-age conditions, such as CD and ODD comorbidity; other variables from childhood, namely, ADHD subtype, temper characteristics ("fearful", "accident prone"), "sexual abuse", "be suspended from school" and family history of ADHD are associated to SUD in ADHD subjects, but not in non-ADHD subjects. Moreover, this study confirms both the higher prevalence of lifetime SUD and greater professional, social and personal impairment in ADHD subjects than in non-ADHD subjects.

Exercise sensitizes skeletal muscle to extracellular ATP for IL-6 expression in mice.

Active skeletal muscle synthesizes and releases interleukin-6 (IL-6), which plays important roles in the organism's adaptation to exercise. Autocrine/paracrine ATP signaling has been shown to modulate IL-6 expression. The aim of this study was to determine whether a period of physical activity modifies the ATP-induced IL-6 expression. BalbC mice were either subject to 5 weeks voluntary wheel running (VA) or kept sedentary (SED). Flexor digitorum brevis muscles were dissected, stimulated with different ATP concentrations (0-100 µM) and IL-6 mRNA levels were measured using qPCR. ATP evoked a concentration-dependent rise in IL-6 mRNA in both SED and VA mice. VA mice however, had significantly higher ATP sensitivity (pD2 pharmacological values: VA=5.58±0.02 vs. SED=4.95±0.04, p<0.05). Interestingly, in VA mice we observed a positive correlation between the level of physical activity and the IL-6 mRNA increase following fiber stimulation with 10 µM ATP. In addition, there were lower P2Y2- and higher P2Y14-receptor mRNA levels in skeletal muscles of VA compared to SED mice, showing plasticity of nucleotide receptors with exercise. These results suggest that exercise increases skeletal muscle ATP sensitivity, a response dependent on the level of physical activity performed. This could have an important role in the mechanisms controlling skeletal muscle adaptation to exercise and training.