Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Exposure to obinutuzumab does not affect outcomes of SARS-CoV-2 infection in vaccinated patients with newly diagnosed advanced-stage follicular lymphoma.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial.

BACKGROUND: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance. PATIENTS AND METHODS: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). RESULTS: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). CONCLUSIONS: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.

Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease.

AIM: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology. METHODS: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aß) 40 and Aß42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aß42/Aß40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome. RESULTS: In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aß42/Aß40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration. CONCLUSIONS: Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration.

Quantitative MRI evaluation of bone marrow in sickle cell disease: relationship with haemolysis and clinical severity.

AIM: To evaluate bone marrow fat fraction using the Dixon technique (FFDix) of magnetic resonance imaging (MRI) as a potential biomarker of haemolysis and clinical severity in the overall assessment and follow-up of sickle cell disease (SCD) patients. MATERIAL AND METHODS: The present study was a cross-sectional study in which healthy individuals and SCD patients (matched for age, sex, and weight) were subjected to MRI of the lumbar spine and pelvis to quantify FFDix in the bone marrow using the Dixon technique. SCD severity was analysed by clinical and laboratory data, and an online calculator. A high degree of haemolysis was defined using the cut-off values haemoglobin (Hb) ≤10 g/dl, lactate dehydrogenase (LDH) ≥325 U/l, reticulocytes ≥3% and total bilirubin (TB) ≥1.2 mg/dl. Pearson's correlation, receiver operating characteristic (ROC) curve and binary logistic regression analysis were performed. RESULTS: Forty-eight SCD patients (26 homozygous: HbSS and 22 compound heterozygous: HbSC) and 48 healthy individuals participated in the study. FFDix was lower in SCD patients than in the control group, showing even lower values in the HbSS subtype and patients with a higher degree of haemolysis. HbSC patients with a higher degree of haemolysis using hydroxyurea (medium dosage 9.8 mg/kg/day) had lower FFDix. ROC curves and odds ratios for detecting patients with a higher degree of haemolysis at the different FFDix measurement sites demonstrated excellent performance: iliac bones (cut-off ≤16.75%, AUC = 0.824, p<0.001), femoral heads (cut-off ≤46.7%, AUC = 0.775, p=0.001), lumbar vertebrae (cut-off ≤7.8%, AUC = 0.755, p=0.002). CONCLUSION: Decreased FFDix is indicative of higher degree of haemolysis and SCD severity with great potential as a non-invasive biomarker contributing to the overall assessment and follow-up of SCD patients.

Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

BACKGROUND: Age-related declines in cognitive function may begin in midlife. PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/µL) were associated with 5-year cognitive decline. CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Odontogenic tumours in a Chilean population: a retrospective study of 544 cases based on 2022 WHO classification.

BACKGROUND: Odontogenic tumours are infrequent lesions. Studies on the frequency of odontogenic tumours from Latin America are scarce. This work aimed to determine the relative frequency of odontogenic tumours in a Chilean population using the 2022 World Health Organization classification. MATERIAL AND METHODS: This is a case series retrospective study. We reviewed 35,530 samples from 1975 to 2022 from the Oral Pathology Referral Institute and the Pathological Anatomy Service, Faculty of Dentistry, University of Chile. We utilized the 2022 World Health Organization classification for histological typification. RESULTS: According to 2022 World Health Organization classification, 544 odontogenic tumours were confirmed. The most frequent odontogenic tumours were: odontoma (n=241; 44.3%), ameloblastoma (n=109; 20.0%) and cemento-ossifying fibroma (n=71; 13.1%). Benign odontogenic tumours corresponded to 538 cases (98.9%) and malignant tumours were only six cases (1.1%). CONCLUSIONS: In our population, odontoma was the most frequent odontogenic tumour followed by ameloblastoma and cemento-ossifying fibroma. Malignant odontogenic tumours were very rare. The results of this study are similar to reports from America, but there are some differences concerning the data from Africa and Asia.

The Sapienza count-down for a healthy and sustainable diet.

Abstract: The prevalence of obesity and of other non-communicable diseases related to overnutrition is significantly increasing in the past few years. Policy makers are called to counteract this pandemic, orienting consumers towards a healthier and more sustainable diet. Most of the proposed initiatives are dedicated to the content of nutrients with "unfavourable" effects but, in fact, focusing the attention only or mainly on single foods or nutrients is not effective in decreasing the incidence/prevalence of non-communicable diseases. Whole dietary patterns play by far a more important role than specific dietary components in promoting health and modulating survival; and the adherence to eating patterns like the Mediterranean diet reduces the risk of non-communicable diseases. The challenge is therefore to be able to transmit information relating to a healthy eating pattern through positive messages in a few simple indications which in turn represent the nutritional, but also the socio-cultural, environmental and economic characteristics of a healthy and sustainable dietary model. The Mediterranean Diet is normally proposed through a graphic depiction that represents a pyramid which is a simple and effective representation but not of immediate impact. For this reason, we are proposing to adopt the "Sapienza Count-down for a Healthy and Sustainable Diet" that will integrate the pyramid with a more immediate approach.

Incidence and Outcomes of Early Cancers After Kidney Transplantation.

Outcomes of early cancers after kidney transplantation are not well-understood. We included recipients of first live and deceased donor kidney transplants who developed de novo cancers in Australia and New Zealand between 1980-2016. We compared the frequency and stage of specific cancer types that developed early (≤12-months) and late (>12-months) post-transplantation. Risk factors for death were evaluated using multivariable Cox regression analyses. Of 2,759 recipients who developed de novo cancer, followed-up for 40,035 person-years, 243 (8.8%) patients were diagnosed with early cancer. Post-transplant lymphoproliferative disease, urinary cancers and melanoma were the most common cancer types (26%, 18%, and 12%) and the majority were either in-situ or locally invasive lesions (55%, 84%, and 86%). Tumors arising early from the gastrointestinal and respiratory systems were uncommon but aggressive, with 40% presenting with metastatic disease at time of diagnosis. Overall, 32% of patients with early cancers died within a median of 4.7 months (IQR:0.6-16) post-diagnosis and 91% were cancer-related deaths. Older recipient and donor age were associated with an increased risk of all-cause death. Early cancers, though infrequent in kidney transplant recipients, are associated with poor outcomes, as nearly 1 in 3 died from cancer-related death; with majority of deaths occurring within 12-months of cancer diagnosis.

Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.

OBJECTIVES: The aim of this analysis was to characterize transmitted drug resistance (TDR) in Strategic Timing of Antiretroviral Treatment (START) study participants by next-generation sequencing (NGS), a sensitive assay capable of detecting low-frequency variants. METHODS: Stored plasma from participants with entry HIV RNA > 1000 copies/mL were analysed by NGS (Illumina MiSeq). TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at three thresholds are reported: > 2%, 5% and 20% of the viral population. RESULTS: Between 2009 and 2013, START enrolled 4684 antiretroviral therapy (ART)-naïve individuals in 35 countries. Baseline NGS data at study entry were available for 2902 participants. Overall prevalence rates of TDR using a detection threshold of 2%/5%/20% were 9.2%/5.6%/3.2% for nucleoside reverse transcriptase inhibitors (NRTIs), 9.2%/6.6%/4.9% for non-NRTIs, 11.4%/5.5%/2.4% for protease inhibitors (PIs) and 3.5%/1.6%/0.1% for INSTI DRMs and varied by geographic region. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%). CONCLUSIONS: Use of NGS in this study population resulted in the detection of a large proportion of low-level variants which would not have been detected by traditional Sanger sequencing. Global surveillance studies utilizing NGS should provide a more comprehensive assessment of TDR prevalence in different regions of the world.

Network meta-analysis of post-exposure prophylaxis randomized clinical trials.

OBJECTIVES: We performed a network meta-analysis of PEP randomized clinical trials to evaluate the best regimen. METHODS: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three-drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir-boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat-boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non-completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow-up and adverse events. RESULTS: Participants were mostly men who have sex with men (n = 832, 75%) with non-occupational exposure to HIV (89.86%). Four-hundred fifty-four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non-completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58-1.56; EVG/c: OR 0.65 95% CI 0.30-1.37; RAL: OR 0.68 95% CI 0.41-1.13; and MVC: OR 0.69 95% CI 0.47-1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non-completion at day 28, switching, lost to follow-up or adverse events and MVC for PEP discontinuations due to adverse events. CONCLUSIONS: Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single-Tablet Regimen.

Upper-lip laser frenectomy with a diode laser in a pediatric patient: a case report.

The case report aims to describe the parameters of performing upper labial frenectomy with the use of diode laser beams without infiltrated local anaesthesia. A 6-year-old patient was referred by the orthodontist for assessment of the upper anterior labial frenum. The dental treatment plan reported only the presence of caries on deciduous teeth and seals on the first permanent molars. The clinical examination reported the presence of a high attachments of labial frenum with a pathologically attachment and the presence of a diastema supports this theory. The laser used to remove the frenulum was a diode laser used with a wavelength of 980 nm with 320 microns of fiber in contact with a power of 2.0 W in continuous wave mode. The clinical examination showed an acceptable healing by secondary intention of the wound and the initial functional recovery of a physiological upper lip movements. The patient reported that the procedure was well tolerated. The diode laser can be used with good result for the removal of pathological frenum. The diode laser can be used in pediatric dentistry because of its application, adequate coagulation, no need for sutures and less inflammation and pain.

The role of periodontal bacteria, Porphyromonas Gingivalis, in Alzheimer's disease pathogenesis and aggravation: a review.

The aim of this study was to establish the role of Porphyromonas gingivalis in Alzheimer's disease. An electronic search of publications was established from three electronic databases: Cochrane, PubMed and Web of Science. The search strategy used a combination of controlled vocabulary and free-text words. Inclusion and exclusion criteria were defined by the authors before the start of the study. The inclusion criteria were: all studies published in English language; in vitro analysis; in vivo on animals and postmortem biopsies on humans; studies analyzing the correlation between periodontal disease and Alzheimer. The search resulted in 262 titles. Only 9 articles were included in the quantitative analysis. An inflammatory status in the oral cavity might be connect to a brain degeneration syndrome such as dementia and AD. However, a strictly connection is still not evincible. More trials are recommended in order to investigate the role of periodontal bacteria and Porphyromonas gingivalis in AD pathogenesis and aggravation.

Genotoxic and mutagenic effects of methyl ether dillapiole on the development of Aedes aegypti (Diptera: Culicidae).

Dillapiole, extracted from Piper aduncum essential oil and its derivatives, has been shown to be a potential alternative to the control of Aedes aegypti, which has become resistant to synthetic insecticides. Methyl ether dillapiole (MED) and temephos (TM) were compared to complement the data on the genotoxicity and developmental changes of Ae. aegypti. Over four generations (G1 -G4 ), third stage larvae were treated with MED at 60, 80 and 100 µg/mL and TM at 0.002, 0.005 and 0.007 µg/mL for 4 h. Adult females were separated to estimate oviposition and hatching rates, and total egg length. Over the four generations, a significant reduction was recorded in oviposition and hatching rates, and in mean egg length (Tukey, P < 0.05), compared with the negative control (NC). Cytological slide preparations were done from adult oocytes and larval neuroblasts. The cumulative effects of genotoxic (bridges, budding and nuclear fragmentation) and mutagenic (micronucleus and chromosomal breakage) damage was observed in the neuroblasts and oocytes of exposed mosquitoes. Developmental changes and damage to the genome of MED-treated Ae. aegypti were greater than those caused by TM. Further studies should focus on understanding the effects of the MED molecule on Ae. aegypti.

The role of dermatology in African patients referred for health treatment in a European centre.

BACKGROUND: Owing to the migratory movement between African and European countries, we have been seeing an increasing number of dermatoses in patients with darker skin phenotypes in our clinical practice. AIM: To evaluate the support provided by outpatient dermatology consultations to such patients and to assess the most frequent dermatoses seen in this population. METHODS: A retrospective 5-year study was conducted in a Portuguese hospital, which is a referral centre to several medical specialities for patients evacuated from Portuguese-speaking African countries, under a specific agreement of international cooperation in health. RESULTS: In total, 116 patients, with a mean age of 38 years, were evaluated. In total, 47 dermatoses were identified, with the 6 most common being fungal infections (12.1%), eczema (9.5%), dyschromias (8.6%), xerosis (6.9%), acne (6%) and hair disorders (6%). CONCLUSIONS: This increased knowledge about the most frequent dermatoses in this population, along with their manifestations and the factors that influence them should allow better diagnosis and therapy.

Building on existing tools to improve chronic disease prevention and screening in public health: a cluster randomized trial.

BACKGROUND: The BETTER (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care) intervention was designed to integrate the approach to chronic disease prevention and screening in primary care and demonstrated effective in a previous randomized trial. METHODS: We tested the effectiveness of the BETTER HEALTH intervention, a public health adaptation of BETTER, at improving participation in chronic disease prevention and screening actions for residents of low-income neighbourhoods in a cluster randomized trial, with ten low-income neighbourhoods in Durham Region Ontario randomized to immediate intervention vs. wait-list. The unit of analysis was the individual, and eligible participants were adults age 40-64 years residing in the neighbourhoods. Public health nurses trained as "prevention practitioners" held one prevention-focused visit with each participant. They provided participants with a tailored prevention prescription and supported them to set health-related goals. The primary outcome was a composite index: the number of evidence-based actions achieved at six months as a proportion of those for which participants were eligible at baseline. RESULTS: Of 126 participants (60 in immediate arm; 66 in wait-list arm), 125 were included in analyses (1 participant withdrew consent). In both arms, participants were eligible for a mean of 8.6 actions at baseline. At follow-up, participants in the immediate intervention arm met 64.5% of actions for which they were eligible versus 42.1% in the wait-list arm (rate ratio 1.53 [95% confidence interval 1.22-1.84]). CONCLUSION: Public health nurses using the BETTER HEALTH intervention led to a higher proportion of identified evidence-based prevention and screening actions achieved at six months for people living with socioeconomic disadvantage. TRIAL REGISTRATION: NCT03052959 , registered February 10, 2017.

Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes.

Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on mechanisms that confer multiple drug resistance. This study investigated the modulating activity of terbinafine promoted by dihydrojasmone and terpinolene against Microsporum canis LM 216, Trichophyton interdigitale H6 and T. interdigitale Δmdr2. The minimum inhibitory concentration (MIC) of test drugs was determined by broth microdilution. The effect of the drugs tested on plasma membrane functionality was analysed. Terbinafine MIC was determined in sub-inhibitory concentrations of monoterpenes. Finally, it was performed an association study with terbinafine and monoterpenes. Dihydrojasmone presented lower MIC values than terpinolene. All fungi were sensitive to terbinafine, starting at 1 µg ml-1 . All tested drugs increased K+ release (P < 0·05), affecting the functionality of the plasma membrane. Dihydrojasmone modulated the sensitivity of all strains against terbinafine, and terpinolene modulated the sensitivity of M. canis LM 216 and T. interdigitale Δmdr2. The monoterpenes and terbinafine drug associations presented synergism. In conclusion, the results suggest that the dihydrojasmone and terpinolene are promising antifungal agents that potentiate the antifungal activity of terbinafine against dermatophytes.

Association between sedentary behavior and bone mass in adolescents.

The effects of sedentary behavior on adolescents' bone health are controversial because, even in normal weight individuals, the excessive time spent in some specific types of these behaviors appears to have no negative effect on bone health. PURPOSE: To analyze the relationship between sedentary behaviors and bone mass in adolescents. METHODS: One hundred four adolescent boys and girls, aged 10 to 14 years, were divided into normal weight and overweight according to weight status. Specific sedentary behaviors (time spent on the Internet for school and non-school purposes, using the computer, watching television, and playing videogames) were assessed by questionnaire, and the total sedentary behavior time by accelerometry. Bone parameters were collected using X-ray absorptiometry, using total and lumbar bone mineral density (BMD) and total and lumbar bone mineral content (BMC) values. RESULTS: In both groups, the time spent on the Internet for non-school purposes was positively correlated to the total and lumbar BMD. Also, while in the overweight group, the time spent using the computer was negatively correlated to lumbar BMD, and the time spent on the Internet for non-school purposes was positively correlated to the total and lumbar BMC, and in the normal weight group, the time spent on the Internet for non-school purposes was positively correlated to lumbar BMC. CONCLUSIONS: Adolescents who spend more time in sedentary behavior, especially using the Internet for non-school purposes, have higher BMD and BMC, while normal weight adolescents who spend more time on the computer have lower BMD.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.