Exploring the link between hedonic overeating and prefrontal cortex dysfunction in the Ts65Dn trisomic mouse model.

Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential "hedonic" overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.

Insular Role in Blood Pressure and Systemic Vascular Resistance Regulation.

OBJECTIVES: The insula is a brain area involved in the modulation of autonomic responses. Previous studies have focused mainly on its heart rate regulatory function, but its role in vascular control is not well defined. Ictal/postictal blood pressure (BP) fluctuations may have a role in the pathogenesis of sudden unexpected death in epilepsy. This study aims to characterize the insular influence on vascular regulation through direct high-frequency electrical stimulation (E-stim) of different insular regions during stereo-electroencephalographic studies. MATERIALS AND METHODS: An observational, prospective study was conducted, involving people with epilepsy who underwent E-stim of depth electrodes implanted in the insular cortex. Patients with anatomical or electrophysiological insular abnormalities, E-stim producing after discharges, or any elicited symptoms were excluded. Variations of BP and systemic vascular resistance (SVR) during the insular stimuli were analyzed, comparing them with those observed during E-stim of control contacts implanted in cortical noneloquent regions and sham stimulations. RESULTS: Fourteen patients were included, five implanted in the right insula and nine in the left. We analyzed 14 stimulations in the right insula, 18 in the left insula, 18 in control electrodes, and 13 sham stimulations. Most right insular responses were hypertensive, whereas most left ones were hypotensive. E-stim of the right insula produced a significant BP and SVR increase, whereas the left insula induced a significant BP decrease without SVR changes. The most remarkable changes were elicited in both posterior insulas, although the magnitude of BP changes was generally low. Control and sham stimulations did not induce BP or SVR changes. CONCLUSION: Our findings on insular stimulation suggest an interhemispheric difference in its vascular regulatory function, with a vasopressor effect of the right insula and a vasodilator effect of the left one.

Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study).

PURPOSE: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. METHODS: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. RESULTS: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. CONCLUSION: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.

Effects of Mixing Energy Drinks With Alcohol on Driving-Related Skills.

BACKGROUND: Energy drinks (EDs) reduce sleepiness and fatigue and improve driving performance whereas alcohol does just the opposite. Although it is a trendy combination among young people, the effects of alcohol mixed with EDs on driving performance have been poorly studied. The aim was to assess if there is an interaction between the effects of both drinks on driving-related skills as well as perceptions about driving ability. METHODS: We conducted a randomized, double-blind, and placebo-controlled 4-way crossover clinical trial. Participants were 16 healthy volunteers. Interventions of 60 g of ethanol and 750 mL of Red Bull (RB) were administered in 2 separated doses. Conditions were alcohol + RB placebo, alcohol + RB, alcohol placebo + RB, and both placebos. Objective performance was assessed using a tracking test and simple reaction time, N-Back, and movement estimation tasks. Additionally, willingness to drive, other subjective effects, and ethanol and caffeine blood concentrations were also measured. RESULTS: Alcohol increased the time outside the road in the tracking test and increased simple reaction time, but the addition of RB had no main or interaction effects on performance. Nonetheless, driving-related skills after alcohol + RB were better than after alcohol alone. Willingness to drive increased with the combination of drinks. RB also reduced alcohol-induced sedation whereas drunkenness did not change. These effects were seen even though alcohol + RB increased alcohol (14.8%) and caffeine plasma concentrations (17.6%). CONCLUSIONS: Mixing EDs with alcohol predisposes consumers to drive under alcohol influence, perhaps in part because EDs counteract its detrimental effects on driving-related skills. Clinicaltrials.gov: NCT02771587.

SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study.

BACKGROUND: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. METHODS: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. RESULTS: From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5-3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. CONCLUSIONS: Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.

Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics.

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.

Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Multiple imputation approach for interval-censored time to HIV RNA viral rebound within a mixed effects Cox model.

We present a method to fit a mixed effects Cox model with interval-censored data. Our proposal is based on a multiple imputation approach that uses the truncated Weibull distribution to replace the interval-censored data by imputed survival times and then uses established mixed effects Cox methods for right-censored data. Interval-censored data were encountered in a database corresponding to a recompilation of retrospective data from eight analytical treatment interruption (ATI) studies in 158 human immunodeficiency virus (HIV) positive combination antiretroviral treatment (cART) suppressed individuals. The main variable of interest is the time to viral rebound, which is defined as the increase of serum viral load (VL) to detectable levels in a patient with previously undetectable VL, as a consequence of the interruption of cART. Another aspect of interest of the analysis is to consider the fact that the data come from different studies based on different grounds and that we have several assessments on the same patient. In order to handle this extra variability, we frame the problem into a mixed effects Cox model that considers a random intercept per subject as well as correlated random intercept and slope for pre-cART VL per study. Our procedure has been implemented in R using two packages: truncdist and coxme, and can be applied to any data set that presents both interval-censored survival times and a grouped data structure that could be treated as a random effect in a regression model. The properties of the parameter estimators obtained with our proposed method are addressed through a simulation study.

High risk and probability of progression to osteoporosis at 10 years in HIV-infected individuals: the role of PIs.

Background: Osteoporotic fractures still remain very infrequent and physicians rarely evaluate bone health. We wanted to assess the magnitude of this problem in the near future by determining the risk and likelihood of progression to osteoporosis. Methods: We estimated the risk of progression to osteopenia/osteoporosis among HIV-infected patients with at least 2 DXA scans (3726 scans from 875 patients). Time-non-homogeneous bidirectional multistate models based on three states (normal bone mineral density, osteopenia and osteoporosis) were used to model the progression of bone mineral density as a function of age and to study the association between the risk of bone loss and antiretroviral use. Results: The HRs associated with age (>45 versus ≤45 years) were: (i) from normal bone mineral density to osteopenia, 0.71 (95% CI 0.45-1.11) for men and 1.06 (95% CI 0.55-2.05) for women; and (ii) from osteopenia to osteoporosis, 0.83 (95% CI 0.51-1.35) for men and 0.99 (95% CI 0.38-2.56) for women. The transition probabilities from osteopenia to osteoporosis over 10 years among men aged 30 and 50 years were 14.9% (95% CI 10.5%-20.4%) and 19% (95% CI 14.3%-24.3%), respectively; and for women, 6.9% (95% CI 3.1%-14.4%) and 30.1% (95% CI 19.8%-41.8%), respectively. An increased osteoporosis risk was observed for PIs and PIs + tenofovir disoproxil fumarate; darunavir was associated with a higher risk of osteoporosis among men (HR 3.9; 95% CI 2-7.5) and women (HR 4.5; 95% CI 1.4-14.7); and atazanavir was associated with a higher risk of osteoporosis among women (HR 4.2; 95% CI 1.3-14). Conclusions: Our results highlight the importance of monitoring bone mineral density given the high probability of progression to osteopenia/osteoporosis, especially in women. In the future, changes in antiretrovirals other than tenofovir, such as PIs, should be recommended to reduce the risk of fracture.

Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1-/- ) and Parp-2-/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1-/- , and Parp-2-/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1-/- and Parp-2-/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention.

Non-Linear Formation of EtG and FAEEs after Controlled Administration of Low to Moderate Doses of Ethanol.

AIMS: Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of alcohol that can be detected in conventional and non-conventional biological matrices for longer periods than alcohol. The aim was to describe the time courses of both biomarkers after ingestion of acute low-moderate doses of ethanol. METHODS: The study design was double-blind, randomized, crossover and controlled with placebo. Participants were distributed in three different cohorts: (a) Cohort-1: two doses of 18 and 30 g of ethanol and placebo were administered to 12 subjects; (b) Cohort-2: two doses of 6 and 12 g of ethanol and placebo were administered to six subjects and (c) Cohort-3: two doses of 24 and 42 g of ethanol and placebo were administered to six subjects. Each participant received two doses of ethanol and placebo. Plasma concentrations (0-6 h) of ethanol and specific FAEEs (palmitic, stearic, linoleic and oleic acid ethyl esters) and urinary concentrations of EtG (0-24 h) were measured. RESULTS: A dose-dependent increase in blood ethanol concentrations was observed. EtG excretion and FAEEs plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. Area under the curve (AUC0-6h) of ethanol concentrations showed a linear trend with non-oxidative metabolites' concentrations. CONCLUSION: The formation rate of ethanol non-oxidative biomarkers does not follow a linear trend, explained mainly by a disproportionate increase in AUC0-6h of ethanol concentrations in relation to dose. This observation should be taken into account when interpreting results in biological matrices in clinical and forensic settings. SHORT SUMMARY: A double-blind, randomized, crossover and controlled study was conducted administering ethanol (6-42 g). Ethyl glucuronide (EtG) excretion and fatty acid ethyl esters (FAEEs) plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. This observation should be taken into account when interpreting biomarker concentrations in clinical settings.

Ethanol induces hydroxytyrosol formation in humans.

Previous studies in animals have shown an increase of hydroxytyrosol (OHTyr), a potent phenolic antioxidant and a minor metabolite of dopamine (also called 3,4-dihydroxyphenylethanol or DOPET), after ethanol intake. The interaction between ethanol and dopamine metabolism is the probable mechanism involved. The aim of the study was to establish the contribution of the dose of ethanol on OHTyr formation. 24 healthy male volunteers were included. Subjects were distributed in three different cohorts and each volunteer received two doses of ethanol or placebo. Doses of ethanol administered were 6, 12, 18, 24, 30 and 42 g. Study design was double-blind, randomized, crossover and controlled. Hydroxytyrosol, tyrosol (Tyr), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) urinary excretion, ethanol plasma concentrations and drunkenness were evaluated along a 6-h period. Urinary excretion of OHTyr and Tyr increased with ethanol administered dose. A reduction in the ratio DOPAC/OHTyr from placebo to the highest dose was observed, compatible with a shift in the dopamine metabolism to preferently produce OHTyr instead of DOPAC. Also a dose-dependent increase in plasma ethanol concentrations and subjective effects was observed. This study demonstrates an endogenous production of OHTyr and Tyr in relation to ethanol administered dose in humans. Biological effects of both phenols from this source should be investigated in future studies.

Deep sclerectomy with supraciliary hema implant (Esnoper® V-2000): results and complications.

The aim was to report the results of deep sclerectomy (DS) with supraciliary hema implant and the influence of the surgical complications on intraocular pressure (IOP). Forty-eight eyes of 41 patients with open angle glaucoma (OAG), who underwent DS with supraciliary hema implant (Esnoper(®) V-2000), were included in this study. A significant IOP reduction was observed, changing from a preoperative mean of 24.6 ± 6.33 mmHg to 16.5 ± 4.4 mmHg (p < 0.001) at 12 months and 16.1 ± 3.4 mmHg (p < 0.001), at 24 months. Similarly, a significant reduction in the number of glaucoma drugs needed was observed, varying from 2.71 to 0.22 (p < 0.001) and 0.4 (p < 0.001), 1 and 2 years after surgery. Goniopuncture with the Nd:Yag Laser was performed in 30 eyes (62.5%) with a mean time between the surgery and the procedure of 150 days, producing a mean IOP reduction of 4.0 mmHg (p < 0.001). The main intraoperative complications were microperforation of the trabeculodescemetic membrane (TDM) in 1 eye (2.08%) The main early postoperative complications were seidel at 24 h in 11 eyes (22.91%), hyphema in 7 eyes (14.58%), choroidal detachment in 3 eyes (6.25%) with macular folds in 2 (4.16%) and need for additional mitomycin injections in 2 eyes (4.16%). All these complications were spontaneously resolved. No correlation between these complications and final IOP was found, but a significant correlation between the presence of hyphema and higher IOP 24 months postoperatively (p = 0.048) was observed. DS with supraciliary hema implant is a safe and effective technique for the management of OAG. The presence of hyphema during the first week after the surgery could be considered as a negative prognostic factor in DS with supraciliary implantation.

Estimation and residual analysis with R for a linear regression model with an interval-censored covariate.

Interval-censored covariates are sometimes encountered in longitudinal studies and considered as possible predictors in a regression model. This paper, motivated by an AIDS study, proposes an implementation in R for the estimation of parameters and the assessment of the assumptions of a linear regression model with an interval-censored covariate. The properties of the parameters estimators and the behavior of three proposed residuals are addressed through two simulation studies. Also, guidelines are provided to check the goodness-of-fit of the fitted model in terms of the length of the censoring interval of the covariate. The methodology is illustrated with real data coming from the AIDS study. R functions and scripts are provided.

Burnout in residents during the first wave of the COVID-19 pandemic: a systematic review and meta-analysis.

Introduction: The high prevalence of burnout in resident physicians is expected to have increased as a result of the expansion of the pandemic. We conducted a systematic review with a meta-analysis of studies conducted during the first wave of the COVID-19 pandemic on burnout in residents and potential associated risk factors. Methods: The search was done in the Web of Science, MEDLINE, Scopus, and Lillac databases (April 2020-October 2021) using a priori protocol based on the PRISMA guidelines. The Newcastle Ottawa Scale was used to assess the risk of bias in the included studies. We estimated the pooled prevalence (95% CI) of burnout and the prevalence ratio (95% CI) of each risk factor associated. Results: We included 23 studies from 451 potential initial articles and those written in the English language; all of the collected studies were cross-sectional with anonymous online surveys, involving 4,998 responders (34%), of which 53.2% were female responders, 51% were R1-2, and 71% were in direct contact with COVID-19 patients. Eighty-seven percent presented a low-to-moderate risk of bias. Publication bias was not shown. The estimated pooled prevalence of burnout was 40% (95% CI = 0.26 - 0.57). Burnout was associated with psychiatry history (PR = 4.60, 95% CI = 1.06 - 20.06). There were no differences by gender, civil status, children in-charge, year of residency, or time exposure to COVID-19. Discussion: The overall prevalence of burnout in residents during the first wave of the pandemic was in line with the results described in this collective before the pandemic. The presence of a psychiatry history was a potential burnout risk factor, suggesting a high vulnerability during the peak of the stress period and the need to implement mental health surveillance for this subgroup.

Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with MRI-negative focal epilepsy.

OBJECTIVE: Coupled with stereo-electroencephalography (SEEG), radiofrequency thermocoagulation (RFTC) has emerged as a therapeutic alternative for patients with refractory focal epilepsy, with proven safe but highly variable results across studies. The authors aimed to describe the outcomes and safety of SEEG-RFTC, focusing on patients with MRI-negative epilepsy. METHODS: A retrospective observational study was conducted on patients evaluated by SEEG in the authors' center. Of 84 total cases, 55 underwent RFTC, with 31 MRI-negative epilepsies that were ultimately included in the study. The primary outcome was freedom from disabling seizures at last follow-up. Secondary outcomes were reduction in seizure frequency (RFTC response = seizure frequency reduction > 50%), peri-interventional complications, and neuropsychological outcomes. Potential factors influencing post-RFTC outcome were considered by comparing different variables between responders and nonresponders. RESULTS: The mean follow-up period was 30.9 months (range 7.1-69.8 months). Three patients underwent subsequent resection/laser interstitial thermal therapy within the 1st year after RFTC failure. All other patients completed a minimum follow-up period of 1 year. Fourteen patients (45.2%) showed at least a 50% reduction in seizure frequency (responders), and 8 were seizure free (25.8% of the whole cohort). One case showed a permanent complication not directly related to thermolesions. Most patients (76%) showed no significant cognitive decline. Electrically elicited seizures (EESs) were observed in all seizure-free patients and were more frequent in responders (p = 0.038). All patients who were seizure free at the 6-month visit maintained their status during long-term follow-up. CONCLUSIONS: SEEG-RFTC is a safe procedure and leads to a good response in many cases of MRI-negative focal epilepsies. One-quarter of the patients were seizure free and almost one-half were responders at the last follow-up. Although these results are still far from those achieved through conventional resection, a nonnegligible proportion of patients may benefit from this one-stage and much less invasive approach. Factors associated with seizure outcome remain to be elucidated; however, responders were significantly more frequent among patients with EESs, and achieving 6 months of seizure freedom appears to predict a good long-term response. In addition, the positive predictive value of RFTC response may be a valuable factor in the decision to proceed to subsequent surgery.

Incidence of infectious diseases and survival among the Roma population: a longitudinal cohort study.

BACKGROUND: Roma ethnicity is greatly affected by tuberculosis (TB), AIDS, injecting drugs use (IDU) and imprisonment. METHODS: We assessed the incidence of several health problems by means of a retrospective cohort study performed in Camp de la Bota, Barcelona (Spain). The 380 individuals included in the 1985 TB outbreak investigation were followed-up until 31 December 2008. One hundred ninety-two subjects (50.5%) were men and 188 (49.5%) women. Information sources included questionnaires taken at the time of this outbreak, a population census and other registries from Barcelona and Catalonia. Cox proportional hazards mixed models were employed in the multivariate survival analysis. RESULTS: By the end of the follow-up, the survival rate was 79.4%; 50 persons (13.1%) had deceased and 28 (7.3%) had emigrated. The incidence of AIDS was 104 cases per 100 000 person-years of follow-up (pyf), IDU was 240 cases pyf, imprisonment was 642 cases pyf and that of TB was 91 cases pyf. Male survival was lower [hazard ratio (HR) 4.22], when the effect of family was taken into account, than when it was not taken into account (HR 3.67). CONCLUSIONS: High incidences of AIDS, TB, IDU, imprisonment and poor survival rates have been observed among Roma. Family was found to be an important factor influencing the survival rates: when not considered, the risk of death among men was underestimated.

Data set on mortality of national basketball association (NBA) players.

In this work, we present a data set on the survival times and mortality rates of all 4374 professional basketball players who participated in the National Basketball Association (NBA) from its inception in 1946 until July 2019 [1]. It contains the data of 412 active and 3962 former players. The data were recorded from different internet sources and include information on each player's position, ethnicity, handedness, ages at NBA debut and career end, height, weight, or number of NBA games. The results of the analysis of a previous data set with the same variables of all NBA players from 1946 to 2015 were recently published by Martinez et al. in 2019 [2]. The information provided in the data set can be useful to better understand the mortality risk among NBA players.

Validation of direct cortical stimulation in presurgical evaluation of epilepsy.

OBJECTIVE: Direct cortical stimulation (DCS) is standard for intracranial presurgical evaluation in drug-resistant epilepsy (DRE). Few studies have reported levels of concordance between spontaneous seizure generators and triggered seizures during DCS. The present work reports validity measures of DCS for detecting the seizure onset zone (SOZ) during stereoelectroencephalography (SEEG). METHODS: We evaluated all patients who underwent SEEG evaluation at our epilepsy center between 2013 and 2019. Data were analyzed using contingency tables. Validity measures of the diagnostic test were computed for all patients evaluated with DCS and for seizure free patients. RESULTS: Fifty-eight consecutive patients were evaluated through DCS. One hundred seventy-three clinical seizures were elicited with DCS. Electroclinical identical to spontaneous seizures were considered true positive (TP) seizures. They showed a high specificity (96.9%) for detecting the SOZ in patients that remained seizure free one year after treatment. Sensitivity was low (23.0%), and a high percentage of false-negative stimulations was documented in the SOZ. The accuracy was 87.9%. CONCLUSIONS: DCS is a technique with high specificity but a low sensitivity for the localization of the SOZ. The DCS validity measures need to be known when considered for surgical decisions. The interpretation of DCS-triggered seizures and the differentiation of true-positive vs false-positive seizures should be carefully evaluated. SIGNIFICANCE: DCS seizure triggering is highly specific for SOZ localization.

BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression.

Background: Major depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge. Methods: A total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained. Results: After the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77). Conclusion: Results suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.