Water-soluble vitamin insufficiency, deficiency and supplementation in children and adolescents with a psychiatric disorder: a systematic review and meta-analysis.

Nutrition is fundamental for brain development, but relatively little is known about water-soluble vitamin (WSV) levels and the effect of supplementation on psychiatry symptoms in children and adolescents (CAD) with psychiatric disorders. Our team systematically reviewed all studies concerning WSV abnormalities or supplementation in CAD with any psychiatric disorder. We searched for original studies published between 1990 and 15/05/2020 which were not based on retrospective chart review and which included WSV blood level measurements or investigated the effect of WSV supplementation on psychiatric symptoms in psychiatric patients aged 18 or under. Forty-two articles were included, 69% of which (N = 29) examined Autism Spectrum Disorders (ASD), with most of these assessing folate or vitamin B12 supplementation (N = 22, 75.9% of ASD studies). Meta-analyses showed significantly lower vitamin B12 levels in ASD and ADHD patients vs. healthy controls (HC), while folate levels were higher in ADHD patients vs. HC. Most of the studies (9/10, 90%) showed a decrease in symptoms as measured by clinical scales after supplementation. There was significant heterogeneity between the studies, however many found different types of vitamin abnormalities in CAD with psychiatric disorders.

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance.

The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms of the condition. Although seizure activity in AD has been mainly viewed as a result of neuronal cell loss and considered to occur in later stages, it is now becoming increasingly clear that aberrant neuronal activity may be more common in patients at earlier stages than previously thought and may trigger and contribute significantly to cognitive defects. Here, we review alterations of inhibitory and excitatory circuits that may lead to overexcitability and early dysregulation of neuronal networks in the context of AD and therapeutic outcomes of restoring excitatory/inhibitory balance.

Arc protein expression after unilateral intracranial self-stimulation of the medial forebrain bundle is upregulated in specific nuclei of memory-related areas.

BACKGROUND: Intracranial Self-Stimulation (ICSS) of the medial forebrain bundle (MFB) is a deep brain stimulation procedure, which has a powerful enhancement effect on explicit and implicit memory. However, the downstream synaptic plasticity events of MFB-ICSS in memory related areas have not been described thoroughly. This study complements previous work studying the effect of MFB-ICSS on the expression of the activity-regulated cytoskeleton-associated (Arc) protein, which has been widely established as a synaptic plasticity marker. We provide new integrated measurements from memory related regions and take possible regional hemispheric differences into consideration. RESULTS: Arc protein expression levels were analyzed 4.5 h after MFB-ICSS by immunohistochemistry in the hippocampus, habenula, and memory related amygdalar and thalamic nuclei, in both the ipsilateral and contralateral hemispheres to the stimulating electrode location. MFB-ICSS was performed using the same paradigm which has previously been shown to facilitate memory. Our findings illustrate that MFB-ICSS upregulates the expression of Arc protein in the oriens and radiatum layers of ipsilateral CA1 and contralateral CA3 hippocampal regions; the hilus bilaterally, the lateral amygdala and dorsolateral thalamic areas as well as the central medial thalamic nucleus. In contrast, the central amygdala, mediodorsal and paraventricular thalamic nuclei, and the habenular complex did not show changes in Arc expression after MFB-ICSS. CONCLUSIONS: Our results expand our knowledge of which specific memory related areas MFB-ICSS activates and, motivates the definition of three functionally separate groups according to their Arc-related synaptic plasticity response: (1) the hippocampus and dorsolateral thalamic area, (2) the central medial thalamic area and (3) the lateral amygdala.

Activation in Children and Adolescents Treated With Selective Serotonin Reuptake Inhibitors: A Weighty Reason?

BACKGROUND: Activation is a behavioral adverse event related to the use of psychotropic medication. Its high incidence in pediatrics and in childhood-onset neuropsychiatric disorders suggests it may be linked to neurodevelopment. However, previous studies have scarcely examined the role that factors relevant to developmental pharmacokinetics, such as body weight, may play in the onset of activation in children and adolescents. METHODS: We conducted a retrospective analysis of hospitalized patients to identify the risk factors for activation in children and adolescents treated with selective serotonin reuptake inhibitors. Our focus was on factors related to development, including body weight, to explore the relationship between activation and neurodevelopmental processes. RESULTS: Among the 139 participants (mean age, 14 ± 2.3 years), activation appeared in 29 (20.9%). Age 12 years or younger and comorbid diagnosis of autism spectrum disorder were associated with statistically significant increases in the risk of activation, but no association was found regarding body weight. CONCLUSIONS: Our findings support the hypothesis that activation is closely linked to brain development processes. Longitudinal studies are needed to explore this line of research further.

Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment.

Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48 h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90 min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48 h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation.

Fibre Intake in Chronic Kidney Disease: What Fibre Should We Recommend?

Chronic kidney disease (CKD) is a major global health problem that challenges all patients' healthcare needs. Fibre consumption benefits kidney patients by acting preventively on associated risk factors, improving intestinal microbiota composition or reducing metabolic acidosis and inflammation. In this review, we focus on increasing fibre consumption and the quality of fibre to recommend, in addition to increasing the consumption of foods that naturally have it in their design, that can resort to fortified foods or fibre supplements. The Western nutritional practice, which is low in fibre and rich in animal proteins, saturated fats, sodium, and sugar, increases the risk of mortality in these patients. On the contrary, patterns with higher consumption of fibre and vegetable proteins, such as the Mediterranean, vegetarian, or Plant dominant low protein diet (PLADO), seem to have a preventive effect on the associated risk factors and influence CKD progression. Until now, the use of fibre supplements has not achieved an evident impact on clinical results. Fibre-rich foods contain other nutrients that reduce cardiovascular risk. Promoting diets richer in vegetables and guaranteeing adequate energy and protein intake is a challenge for the multidisciplinary teams involved in the standard of care for CKD.

DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results.

PURPOSE: The search for predictors of antidepressant response is gaining increasing attention, with epigenetic markers attracting a great deal of interest. We performed a genome-wide study assessing baseline differences in DNA methylation between Responders and Non-Responders. PATIENTS AND METHODS: Twenty-two children and adolescents, receiving fluoxetine treatment for the first time, were classified as Responders or Non-Responders according to CGI-I score after 8 weeks of fluoxetine treatment. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC BeadChip Kit and analyzed using the Chip Analysis Methylation Pipeline (ChAMP). RESULTS: We identified 21 CpG sites significantly (FDR<0.05) associated with fluoxetine response that showed meaningful differences (Δß> ±0.2) in methylation level between Responders and Non-Responders. Two genes, RHOJ (Ras Homolog Family Member J) and OR2L13 (Olfactory Receptor family 2 subfamily L member 13), presented more than one significant CpG sites. CONCLUSION: Our findings provide new insights into the molecular mechanisms underlying the complex phenotype of antidepressant response, indicating that methylation at specific genes could be a promising biomarker that needs further replication in large cohorts.

Response to fluoxetine in children and adolescents: a weighted gene co-expression network analysis of peripheral blood.

The inconclusive and non-replicated results of pharmacogenetic studies of antidepressant response could be related to the lack of acknowledgement of its mechanism of action. In this scenario, gene expression studies provide and interesting framework to reveal new candidate genes for pharmacogenetic studies or peripheral biomarkers of fluoxetine response. We propose a system biology approach to analyse changes in gene expression induced by eight weeks of treatment with fluoxetine in peripheral blood. 21 naïve child and adolescents participated in the present study. Our analysis include the identification of gene co-expression modules, using Weighted Gene Co-expression Network Analysis (WGCNA), followed by protein-protein interaction (PPi) network construction coupled with functional annotation. Our results revealed two modules of co-expression genes related to fluoxetine treatment. The constructed networks from these modules were enriched for biological processes related to cellular and metabolic processes, cell communication, immune system processes, cell death, response to stimulus and neurogenesis. Some of these processes, such as immune system, replicated previous findings in the literature, whereas, neurogenesis, a mechanism proposed to be involved in fluoxetine response, had been identified for first time using peripheral tissues. In conclusion, our study identifies several biological processes in relation to fluoxetine treatment in peripheral blood, offer new candidate genes for pharmacogenetic studies and valuable markers for peripheral moderator biomarkers discovery.

Autoantibodies, elevated cytokines, and neurocognitive abnormalities in offspring of women with systemic lupus erythematosus: comparison with healthy controls.

INTRODUCTION: Research describes higher incidence of neurodevelopmental disorders and learning disabilities in offspring of women affected by lupus. Factors implied are pregnancy and delivery adversities and exposure to maternal antibodies and cytokines. Little is known about the offspring immunological condition or the relation between offspring and maternal condition. OBJECTIVES: This study was conducted in order to analyze immunological configuration, psychopathology, and neuropsychological performance of young offspring of women with lupus, in comparison with healthy controls and in relation to maternal psychophysical condition. METHODS: Twenty-one offspring aged 8-17 of 17 women with lupus and 34 controls were recruited. Pregnancy conditions, stress factors, and immunological, psychopathological, and neuropsychological characteristics were compared. Immunological tests included standard lupus screening, lupus-related autoantibodies, antibodies against GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR) (anti-DWEYS Ab), and levels of ten cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GMCSF, IFN-γ, TNF-α). RESULTS: Offspring had lower leukocyte count (p = 0.001) and higher levels of anti-dsDNA Ab (p = 0.022), anti-DWEYS-GluN2 Ab (p < 0.001), and eight cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α-all p < 0.001-and IFN-γ, p = 0.026) than controls. Their cytokine levels did not differ from their mothers'; 23.9% of offspring met the criteria for a clinical psychiatric diagnosis. No differences were found in intelligence measures. Various neuropsychological scores correlated inversely with maternal psychophysical health. CONCLUSIONS: Offspring's profile suggests proinflammatory and autoimmune activation. Their rate of psychiatric diagnosis appears higher than in the general population, and their cognitive performance is related to maternal psychophysical health. Longitudinal research might investigate whether immunological and psychosocial conditions influence psychopathology and cognition. Graphical abstract The hypothesized sequence for physical and neuropsychological development for the SLE offspring.

The Notijoves Project: Protocol for a Randomized Controlled Trial About New Communication Technologies and Gamification to Promote Partner Notification of Sexually Transmitted Infections Among Young People.

BACKGROUND: An increase in sexually transmitted infections (STIs) as well as an increase in the use of new information and communication technologies among young people in Catalonia is the inspiration behind the idea of designing a smartphone app to promote partner notification of STIs. OBJECTIVE: The main objective of this study is to design a Web-based tool adapted to smartphones for partner notification of STIs among youth who are 16 to 24 years old. Additionally, the objective is to evaluate the Web-based tool's role in increasing the patient referral partner notification. METHODS: This is a multicenter randomized controlled trial with a proportional stratification of the sample by center and random allocation of participants to the 3 arms of the study (simple Web-based intervention, game Web-based intervention, and control). This study is being conducted by midwives, gynecologists, and physicians in the sexual and reproductive areas of the primary health care centers. RESULTS: The primary outcome measure is the number and proportion of partner notifications. Additional outcome measures are the yield of early diagnosis and treatment of those exposed and infected, acceptability, barriers, and preferences for partner notification. Expected results include an increase in the yield of partner notification, early diagnosis and treatment among youth using Web-based interventions compared with those receiving the traditional advice to notify, and a description of sexual networks among those participating in the study. CONCLUSIONS: The Notijoves is expected to have a sustainable positive impact in the partner notification practice among youth and contribute to increasing the awareness of STI prevention. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12896.

[Sexually transmitted infections in Barcelona beyond 2000]. / Infecciones de transmisión sexual en Barcelona más allá del 2000.

BACKGROUND AND OBJECTIVE: Information about sexually transmitted infections (STI) in Barcelona is scarce. Sexual risk behaviors and some STI have recently increased. METHOD: Descriptive study of STI diagnosed at the STI Unit of Barcelona between 2001 and 2002. RESULTS: Some STI were more frequent among homosexual men. HIV coinfection in patients with syphilis was seen in 10/18 homosexual men and 1/10 heterosexuals (p = 0.04). CONCLUSIONS: There is a resurgence of some STI in Barcelona. New preventive interventions are needed, especially addressed to homosexual men.

Consumo de carbohidratos y valor de transaminasas hepáticas / CARBOHYDRATE CONSUMPTION AND VALUE OF LIVER TRANSAMINASES

Introducción: la dieta influye en el metabolismo y la estructura del hígado. Cada nutriente actúa sobre éste en forma diferente, y en el caso de los carbohidratos, la influencia específica sobre este órgano se explica por medio de diferentes mecanismos. Cuando la función o la estructura del hígado varían, estos cambios se revelan en ciertos parámetros bioquímicos. Objetivos: el propósito de este trabajo es establecer si existe relación entre el consumo de carbohidratos y el valor de transaminasas hepáticas en pacientes sanos del Sanatorio Adventista del Plata, entre julio y setiembre de 2016. Materiales y métodos: a los sujetos evaluados se les realizó una frecuencia de consumo para conocer su ingesta alimentaria y se obtuvo el valor de la AST, ALT y GGT a partir de sus exámenes de laboratorio. Resultados: el 71,4% de las personas con el valor más alto de AST presentó una ingesta sobreadecuada de carbohidratos. La diferencia entre el consumo de alimentos altos en FODMAP y el promedio del valor de AST fue estadísticamente significativa. El 42,9% de las personas que presentó mayores valores de AST tuvo una ingesta elevada de fibra dietética. Se encontró asociación significativa entre la combinación de proteína y azúcar refinada con el valor de ALT y GGT. Conclusiones: el consumo de carbohidratos se asocia con el valor de AST y no con las otras transaminasas. Existe diferencia entre el consumo de alimentos altos en FODMAP y el promedio del valor de la AST. No hay asociación entre el índice glucémico, el consumo de fibra dietética y el valor de las transaminasas. La combinación de proteína y azúcar refinada se asocia con el valor de ALT y GGT.

Multiple site study of recent atmospheric metal (Pb, Zn and Cu) deposition in the NW Iberian Peninsula using peat cores.

In order to estimate atmospheric metal deposition in Southern Europe since the beginning of the Industrial Period (~1850 AD), concentration profiles of Pb, Zn and Cu were determined in four (210)Pb-dated peat cores from ombrotrophic bogs in Serra do Xistral (Galicia, NW Iberian Peninsula). Maximum metal concentrations varied by a factor of 1.8 for Pb and Zn (70 to 128µgg(-1) and 128 to 231µgg(-1), respectively) and 3.5 for Cu (11 to 37µgg(-1)). The cumulative metal inventories of each core varied by a factor of 3 for all analysed metals (132 to 329µgcm(-2) for Pb, 198 to 625µgcm(-2) for Zn and 22 to 69µgcm(-2) for Cu), suggesting differences in net accumulation rates among peatlands. Although results suggest that mean deposition rates vary within the studied area, the enhanced (210)Pb accumulation and the interpretation of the inventory ratios ((210)Pb/Pb, Zn/Pb and Cu/Pb) in two bogs indicated that either a record perturbation or post-depositional redistribution effects must be considered. After correction, Pb, Zn and Cu profiles showed increasing concentrations and atmospheric fluxes since the mid-XX(th) century to maximum values in the second half of the XX(th) century. For Pb, maximum fluxes were observed in 1955-1962 and ranged from 16 to 22mgm(-2)yr(-1) (mean of 18±1mgm(-2)yr(-1)), two orders of magnitude higher than in the pre-industrial period. Peaks in Pb fluxes in Serra do Xistral before the period of maximum consumption of leaded petrol in Europe (1970s-1980s) suggest the dominance of local pollutant sources in the area (i.e. coal mining and burning). More recent peaks were observed for Zn and Cu, with fluxes ranging from 32 to 52mgm(-2)yr(-1) in 1989-1996, and from 4 to 9mgm(-2)yr(-1) in 1994-2001, respectively. Our results underline the importance of multi-core studies to assess both the integrity and reliability of peat records, and the degree of homogeneity in bog accumulation. We show the usefulness of using the excess (210)Pb inventory to distinguish between differential metal deposition, accumulation or anomalous peat records.

How common is delayed cyclosporine absorption following liver transplantation?

The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA > or =10 mg/kg/day (C(2) monitoring) and in 15 maintenance patients. Patients were categorized as 'normal' absorbers (C(2) exceeding C(4) and C(6)) or 'delayed' absorbers (C(4) or C(6) exceeding C(2)), and as 'good' (>800 ng/mL at C(0), C(2), C(4), or C(6)) or 'poor' absorbers (C(0), C(2), C(4) and C(6) <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had 'normal' CsA absorption and 12 (44%) 'delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6/15, 40%) or delayed (5/12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C(4). Mean C(0) level was significantly higher in delayed absorbers (282 +/- 96 ng/mL) than in normal absorbers (185 +/- 88 ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C(2) > C(4)) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C(4) in addition to C(2) differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided.