Changes in neuroinflammatory markers and microglial density in the hippocampus and prefrontal cortex of the C58/J mouse model of autism.

Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions with complex origins. Individuals with ASD present various neurobiological abnormalities, including an altered immune response in the central nervous system and other tissues. Animal models like the C58/J inbred mouse strain are used to study biological characteristics of ASD. This strain is considered an idiopathic autism model because of its demonstrated reduced social preference and repetitive behaviours. Notably, C58/J mice exhibit alterations in dendritic arbour complexity, density and dendritic spines maturation in the hippocampus and prefrontal cortex (PFC), but inflammatory-related changes have not been explored in these mice. In this study, we investigated proinflammatory markers in the hippocampus and PFC of adult male C58/J mice. We discovered elevated levels of interferon gamma (IFN-γ) and monocyte chemoattractant protein 1 (MCP-1) in the hippocampus, suggesting increased inflammation, alongside a reduction in the anti-inflammatory enzyme arginase 1 (ARG1). Conversely, the PFC displayed reduced levels of TNF-α and MCP-1. Microglial analysis revealed higher levels of transmembrane protein 119 (TMEM119) and increased microglial density in a region-specific manner of the autistic-like mice, particularly in the PFC and hippocampus. Additionally, an augmented expression of the fractalkine receptor CX3CR1 was observed in the hippocampus and PFC of C58/J mice. Microglial morphological analysis shows no evident changes in the hippocampus of mice with autistic-like behaviours versus wild-type strain. These region-specific changes can contribute to modulate processes like inflammation or synaptic pruning in the C58/J mouse model of idiopathic autism.

Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

GSK-3ß orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo.

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3ß) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3ß-overexpressing newborn neurons show an increased number and altered size of Gephyrin+ postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3ß overexpression triggers a depletion of Parvalbumin+ interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3ß is dysregulated.

Beyond forced exhalation: impulse oscillometry as a promising tool for bronchial hyperresponsiveness evaluation.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.

The emotional well-being of Long COVID patients in relation to their symptoms, social support and stigmatization in social and health services: a qualitative study.

BACKGROUND: Long COVID patients have experienced a decline in their quality of life due to, in part but not wholly, its negative emotional impact. Some of the most prevalent mental health symptoms presented by long COVID patients are anxiety, depression, and sleep disorders. As such, the need has arisen to analyze the personal experiences of these patients to understand how they are managing their daily lives while dealing with the condition. The objective of this study is to increase understanding about the emotional well-being of people diagnosed with long COVID. METHODS: A qualitative design was created and carried out using 35 patients, with 17 participants being interviewed individually and 18 of them taking part in two focus groups. The participating patients were recruited in November and December 2021 from Primary Health Care (PHC) centers in the city of Zaragoza (Northern Spain) and from the Association of Long COVID Patients in Aragon. The study topics were emotional well-being, social support networks, and experience of discrimination. All an inductive thematic content analyses were performed iteratively using NVivo software. RESULTS: The Long COVID patients identified low levels of self-perceived well-being due to their persistent symptoms, as well as limitations in their daily lives that had been persistent for many months. Suicidal thoughts were also mentioned by several patients. They referred to anguish and anxiety about the future as well as a fear of reinfection or relapse and returning to work. Many of the participants reported that they have sought the help of a mental health professional. Most participants identified discriminatory situations in health care. CONCLUSIONS: It is necessary to continue researching the impact that Long COVID has had on mental health, as well as to provide Primary Health Care professionals with evidence that can guide the emotional treatment of these patients.

Prescription patterns of somatostatin analogs in patients with acromegaly and neuroendocrine tumors.

PURPOSE: Acromegaly and neuroendocrine tumors are rare diseases that, under certain conditions, can be treated with somatostatin analogs. The aim was to determine the prescription patterns of somatostatin analogs in a group of patients with acromegaly and neuroendocrine tumors affiliated with the Colombian Health System. METHODS: A retrospective study. A cohort of patients from a drug dispensing database that collected all prescriptions of long-acting somatostatin analogs (octreotide, lanreotide, pasireotide). Sociodemographic variables, clinical variables (diagnosis and comorbidities) and pharmacological therapy variables (dose, changes, persistence of use, comedications) were considered. RESULTS: A total of 213 patients were identified, including 139 (65.3%) with acromegaly and 74 (34.7%) with neuroendocrine tumors. There was a predominance of women (58.7%) and a mean age of 59.7 ± 14.5 years. The most commonly used medications were lanreotide autogel (n = 107; 50.2%), octreotide LAR (n = 102; 47.9%) and pasireotide LAR (n = 4; 1.9%). During follow-up, 11.3% of patients experienced modifications of therapy, with a mean duration from the beginning of treatment to the change in medication of 25 ± 15.9 months. A total of 48.9% of the patients with acromegaly and 87.1% of individuals with neuroendocrine tumors received maximum approved doses of the drug. CONCLUSION: Patients with acromegaly and neuroendocrine tumors in Colombia are mainly women and are most frequently treated with lanreotide autogel for acromegaly and with octreotide LAR for neuroendocrine tumors. In addition, a high proportion are managed with maximum doses of long-acting somatostatin analogs.

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study.

BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.

Pathways to adverse pregnancy outcomes: exploring the mediating role of intimate partner violence and depression: results from a South African rape cohort study.

Adverse pregnancy outcomes (APOs) are common occurrences that contribute to negative maternal and child health outcomes. Our aim was to test the hypothesis that trauma exposure and depression are drivers of the better-recognised risk factors for miscarriage, abortion and stillbirths. Our comparative cohort study based in Durban, South Africa recruited women who reported a recent rape (n = 852) and those who had never experienced rape (n = 853), with follow-up for 36 months. We explored APOs (miscarriage, abortion or stillbirth) among those having a pregnancy during follow-up (n = 453). Potential mediators were baseline depression, post-traumatic stress symptoms, substance abuse, HbA1C, BMI, hypertension and smoking. A structural equation model (SEM) was used to determine direct and indirect paths to APO. Overall, 26.6% of the women had a pregnancy in the follow-up period and 29.4% ended in an APO, with miscarriage (19.9%) the most common outcome, followed by abortion (6.6%) and stillbirths (2.9%). The SEM showed two direct pathways from exposure to childhood trauma, rape and other trauma, to APO which were ultimately mediated by hypertension and/or BMI, but all paths to BMI were mediated by depression and IPV-mediated pathways from childhood and other trauma to hypertension. Food insecurity mediated a pathway from experiences of trauma in childhood to depression. Our study confirms the important role of trauma exposure, including rape, and depression on APOs, through their impact on hypertension and BMI. It is critical that violence against women and mental health are more systematically addressed in antenatal, pregnancy and postnatal care.

A pilot randomised controlled trial on the effectiveness of infant massage on the acceptance, commitment and awareness of influence in parents of babies with Down syndrome.

BACKGROUND: The emotional state of parents of babies with Down syndrome affects their babies' development and their parent-child bonding. The aim for this study was to conduct a pilot randomised controlled evaluation of the effect of infant massage on parents of babies with Down syndrome. METHODS: This pilot study compared two groups (intervention and control), each with 16 parents of babies with Down syndrome. Indices of acceptance, engagement and awareness of influence were measured at two different time points (pre-test and after 5 weeks) using the 'This Is My Baby' Interview. The allocation of families to each group was randomised. The experimental group performed infant massage, applied by the parents, for 5 weeks, every day for at least 10 min. The massage protocol was based on the methodology created by Vimala McClure. Parents in the control group received the intervention after completion of the study. RESULTS: The indices of acceptance, commitment and awareness of influence improved in the experimental group and in the control group. The 2 × 2 mixed-model analysis of variance indicates a statistically significant group-by-time interaction for all indices (P < 0.001), which was significantly higher in the experimental group than in the control group. CONCLUSIONS: The application of infant massage, by parents to their babies, improves the rates of acceptance, commitment and awareness of influence of parents of babies with Down syndrome in the short term.

Meta-analysis of small for gestational age births and disinfection byproduct exposures.

BACKGROUND: Some epidemiological studies show associations between disinfection byproducts (DBPs) and adverse developmental outcomes. OBJECTIVES: We undertook a meta-analysis of epidemiological studies on maternal exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) and risk of small for gestational age (SGA) birth. METHODS: We identified forty-five publications including two reports and five theses via a 2020 literature search. Nineteen study populations from 16 publications met the inclusion criteria and were systematically evaluated. Effect measures were pooled using random effects meta-analytic methods along with cumulative, sub-group and meta-regression analyses to examine between-study heterogeneity and variation in risk across different DBP measures. RESULTS: We detected a small increased risk for SGA with exposure to the sum of four (i.e., THM4) THM4 (odds ratio (OR) = 1.07; 95%CI: 1.03, 1.11), chloroform (OR = 1.05; 95%CI: 1.01, 1.08), bromodichloromethane (OR = 1.08; 95%CI: 1.05, 1.11) and the sum of the brominated THM4 (OR = 1.05; 95%CI: 1.02, 1.09). Larger ORs were detected for the sum of five haloacetic acids (i.e., HAA5) (OR = 1.12; 95%CI: 1.01, 1.25), dichloroacetic acid (OR = 1.25; 95%CI: 1.01, 1.41) and trichloroacetic acid (OR = 1.21; 95%CI: 1.07, 1.37). We detected larger SGA risks for several THM4 among the prospective cohort and case-control studies compared to retrospective cohorts and for the SGA3/5% (vs. SGA10%) studies. The THM4 meta-regression showed associations between SGA and the total quality score based on categorical or continuous measures. For example, an OR of 1.03 (95%CI: 1.01, 1.06) was detected for each 10-point increase in the study quality score based on our systematic review. CONCLUSIONS: We detected a small increased risk of SGA based on 18 THM4 study populations that was comparable to a previous meta-analysis of eight THM4 study populations. We also found increased risks for other THM4 and HAA measures not previously examined; these results were robust after accounting for outliers, publication bias, type of SGA classification, different exposure windows, and other factors.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods.

BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.

Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability.

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

Assessment of antibodies against three zoonotic bacteria and associated risk factors in pig farms in Colombia. / Evaluación de anticuerpos frente a tres bacterias zoonóticas y factores de riesgo asociados en explotaciones porcinas de Colombia.

The aim of this study was to determine the seroprevalence of Salmonella spp., Mycobacterium bovis and Brucella spp., together with associated risk factors, in pigs from various farms in seven regions of Colombia. A total of 350 blood samples were obtained from pigs at different stages in the production cycle of 23 farms, which were tested using the enzyme-linked immunosorbent assay (ELISA) diagnostic kits Pigtype®-Salmonella Ab (Qiagen®, Hilden, Germany), INgezim TB porcine and INgezim Brucella porcine (Ingenasa®, Madrid, Spain). The overall seroprevalence for Salmonella spp. was 42.85% (n = 150) and, for M. bovis, it was 5.42% (n = 19). No positive samples were detected for Brucella spp. In the farms evaluated, the presence of pests, such as rodents, was found to be the management variable with a statistically significant association with seropositivity for Salmonella spp. and M. bovis. The results suggest that, at some point in the primary production cycle, pigs came into contact with zoonotic bacteria, resulting in seropositivity, which may pose a risk to public health and national pig production.

Les auteurs présentent les résultats d'une étude menée en Colombie pour déterminer la prévalence sérologique de Salmonella spp., de Mycobacterium bovis et de Brucella spp. et d'identifier les facteurs de risques associés chez les porcs de différents élevages répartis dans sept régions du pays. Au total, 350 prélèvements sanguins de porcs en différentes phases du cycle de production et provenant de 23 exploitations ont été analysés en utilisant les kits de diagnostic suivants : test immuno-enzymatique (ELISA) Pigtype®-Salmonella Ab (Qiagen®, Hilden, Allemagne), INgezim TB porcina et INgezim Brucella porcina (Ingenasa®, Madrid, Espagne). La prévalence sérologique globale de Salmonella spp. était de 42,85 % (n = 150) et celle de M. bovis de 5,42 % (n = 19) ; aucun échantillon n'a été trouvé positif pour Brucella spp. En ce qui concerne les facteurs en lien avec la gestion des élevages, une corrélation significative au plan statistique a été observée dans les exploitations étudiées entre la présence de ravageurs (rongeurs notamment) et l'apparition d'anticorps dirigés contre Salmonella spp. et M. bovis. Les résultats obtenus laissent penser que les porcs ont été exposés à ces bactéries zoonotiques à un moment ou un autre du cycle de production primaire, ce qui a déclenché l'apparition d'anticorps ; il s'agit d'une situation à risque tant pour la santé publique que pour la filière porcine du pays.

El objetivo del presente estudio fue determinar la seroprevalencia respectoa Salmonella spp., Mycobacterium bovis y Brucella spp., junto con los factores de riesgo asociados, en porcinos de diferentes explotaciones de producción en siete regiones de Colombia. Se obtuvieron 350 muestras sanguíneas de porcinos de diferentes etapas del ciclo productivo provenientes de 23 explotaciones,y estas fueron analizadas utilizando los estuches de ensayo inmunoenzimático (ELISA) para diagnóstico Pigtype®-Salmonella Ab (Qiagen®, Hilden, Alemania), INgezim TB porcina e INgezim Brucella porcina (Ingenasa®, Madrid, España). La seroprevalencia general respecto a Salmonella spp. fue del 42,85% (n = 150),y para M. bovis, del 5,42% (n = 19); no se detectó ninguna muestra positiva respecto a Brucella spp. Se determinó que en las explotaciones evaluadas, la presencia de plagas, como los roedores, fue la variable de manejo con asociación estadísticamente significativa a la seropositividad respecto a Salmonella spp.y a M. bovis. Los resultados obtenidos sugieren que, en algún momento del ciclo de producción primaria, los cerdos estuvieron en contacto con las bacterias zoonóticas frente a las que se obtuvo seropositividad, lo cual puede representar un riesgo para la salud pública y la producción porcina a nivel nacional.

Lack of confidence interval reporting in dermatology: a call to action.

BACKGROUND: Confidence intervals (CIs) offer a complete and intuitive presentation of results and are more informative than P-values. The current prevalence of CI reporting in the dermatology literature has not been discussed. OBJECTIVES: To evaluate CI reporting prevalence in the dermatology literature, factors predicting reporting and to compare CI reporting in the dermatology literature with dermatology research in the New England Journal of Medicine (NEJM). METHODS: MEDLINE was queried for trials and observational studies published from 2007 to 2017 in six dermatology journals with varying impact factors: British Journal of Dermatology, Journal of Investigative Dermatology, JAMA Dermatology, Journal of the American Academy of Dermatology, European Journal of Dermatology and Journal of Cosmetic Dermatology. Randomly selected studies were reviewed to calculate CI reporting prevalence, and logistic regression identified factors predictive of CI reporting. RESULTS: Of 97 studies meeting the inclusion criteria, only 21 (22%; 95% CI 14-31%) reported CIs for the primary outcome. Of the remaining 76 studies, 43 reported a measure of variance (57%; 95% CI 45-67%). More recent year of publication was the strongest predictor for CI reporting [odds ratio 1·44; 95% CI 1·10-1·89 (P = 0·01)] in multivariable analysis. CI reporting in NEJM was significantly higher than in the dermatology literature (64% vs. 22%; P < 0·001). CONCLUSIONS: CI reporting in the dermatology literature is low. We urge both dermatology journals and researchers to improve clinical interpretation of study results by taking steps to increase CI reporting.

Differences in the regulation of inflammatory pathways in adolescent- and adult-onset first-episode psychosis.

A precise description of the inflammatory response in first-episode psychosis (FEP) by age of onset does not exist. We explored baseline and 6-month follow-up differences in the pro/anti-inflammatory balance in plasma and peripheral blood mononuclear cells in adolescent-onset FEP (≤ 18 y.o., N = 27) and adult-onset FEP (≥ 25 y.o., N = 43) using non-parametric 1-category ANCOVA, with age group as an independent variable and values of pro- and anti-inflammatory markers at baseline and at follow-up as dependent variables. We used a non-parametric repeated-measures mixed-effects model to explore the baseline/6-month change in pro- and anti-inflammatory markers within adolescent- and adult-onset groups, exploring differential trajectories of change by means of the interaction of time by age-of-onset group. Levels of the nuclear transcription factor (NFκB), a master regulator of the inflammatory and oxido/nitrosative status of cells, were higher in adolescent-onset FEP both at baseline and after 6 months. During follow-up, we found further increases in levels of soluble inflammatory markers (PGE2 and NO2-) only in adolescent-onset FEP. In contrast, in adult-onset FEP, the expression of inducible NO synthase (iNOS), which is also pro-inflammatory, tended to decrease, with no further increase in other pro-inflammatory markers. Significant differences in the direction of change by age-of-onset cohort exist only for NFκB (F = 4.165, df = 2, 70.95, p = 0.019). Our results support the existence of changes in the pro/anti-inflammatory balance in FEP depending on the neurodevelopmental stage at illness onset. These results also suggest that inflammation may be a potential therapeutic target in adolescent-onset FEP.

Growth hormone protects against kainate excitotoxicity and induces BDNF and NT3 expression in chicken neuroretinal cells.

There is increasing evidence to suggest a beneficial neuroprotective effect of growth hormone (GH) in the nervous system. While our previous studies have largely focused on retinal ganglion cells (RGCs), we have also found conclusive evidence of a pro-survival effect of GH in cells of the inner nuclear layer (INL) as well as a protective effect on the dendritic trees of the inner plexiform layer (IPL) in the retina. The administration of GH in primary neuroretinal cell cultures protected and induced neural outgrowths. Our results, both in vitro (embryo) and in vivo (postnatal), showed neuroprotective actions of GH against kainic acid (KA)-induced excitotoxicity in the chicken neuroretina. Intravitreal injections of GH restored brain derived neurotrophic factor (BDNF) expression in retinas treated with KA. In addition, we demonstrated that GH over-expression and exogenous administration increased BDNF and neurotrophin-3 (NT3) gene expression in embryonic neuroretinal cells. Thus, GH neuroprotective actions in neural tissues may be mediated by a complex cascade of neurotrophins and growth factors which have been classically related to damage prevention and neuroretinal tissue repair.

Selective modification of fluciclovine (18F) transport in prostate carcinoma xenografts.

We investigated if previously demonstrated inhibition of fluciclovine (18F) in vitro could be replicated in a PC3-Luc xenograft mouse model. Following intratumoral injection of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), alpha-(methylamino)isobutyric acid (MeAIB) or saline, fluciclovine PET tumor-to-background activity was 43.6 (± 5.4)% and 25.3 (± 5.2)% lower in BCH (n = 6) and MeAIB (n = 5) injected PC3 Luc xenografts, respectively, compared to saline-injected controls (n = 2). Partial inhibition of fluciclovine uptake by BCH and MeAIB can be demonstrated in vivo similar to previous in vitro modeling.

Cadmium and cadmium-tolerant soil bacteria in cacao crops from northeastern Colombia.

AIMS: This research aims to assess total-cadmium soil content and microbiological aspects to understand the dynamics of culturable cadmium-tolerant bacteria (CdtB) in cacao soils from northeastern Colombia. METHODS AND RESULTS: An integration of inverted dish plating, Cd determination and a microcalorimetry assay (IMC) was carried out. A farm in Boyacá showed the highest level of total soil Cd (3·74 mg kg-1 ) followed by farms in Santander and Arauca (2·76 and 1·16 mg kg-1 , respectively). Coefficient of determination between total soil Cd and CFU of CdtB was high (R2  = 0·83) for the farm in Boyacá. Moreover, a pool of 129 CdtB was isolated, and phylogeny of 21 CdtB was discussed. Among CdtB strains isolated, Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Qmax of 2·21 and 2·32 J at 6 and 24 mg l-1 of CdCl2 ), with an immobilization rate of 0·220 mg kg-1  h-1 . CONCLUSIONS: Among CdtB strains isolated, Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Qmax of 2·21 and 2·32 J at 6 and 24 mg l-1 of CdCl2 ), with an immobilization rate of 0·220 mg kg-1  h-1 . SIGNIFICANCE AND IMPACT OF THE STUDY: Nothing is known about soil CdtB in cacao. Our data showed that CdtB such as Enterobacter sp. has high immobilization capacity. Furthermore, the otavite found in situ might be mineralized due to the bacterial metabolic activity of CdtB.

An innovative approach to the assessment of hydro-political risk: A spatially explicit, data driven indicator of hydro-political issues.

Competition over limited water resources is one of the main concerns for the coming decades. Although water issues alone have not been the sole trigger for warfare in the past, tensions over freshwater management and use represent one of the main concerns in political relations between riparian states and may exacerbate existing tensions, increase regional instability and social unrest. Previous studies made great efforts to understand how international water management problems were addressed by actors in a more cooperative or confrontational way. In this study, we analyze what are the pre-conditions favoring the insurgence of water management issues in shared water bodies, rather than focusing on the way water issues are then managed among actors. We do so by proposing an innovative analysis of past episodes of conflict and cooperation over transboundary water resources (jointly defined as "hydro-political interactions"). On the one hand, we aim at highlighting the factors that are more relevant in determining water interactions across political boundaries. On the other hand, our objective is to map and monitor the evolution of the likelihood of experiencing hydro-political interactions over space and time, under changing socioeconomic and biophysical scenarios, through a spatially explicit data driven index. Historical cross-border water interactions were used as indicators of the magnitude of corresponding water joint-management issues. These were correlated with information about river basin freshwater availability, climate stress, human pressure on water resources, socioeconomic conditions (including institutional development and power imbalances), and topographic characteristics. This analysis allows for identification of the main factors that determine water interactions, such as water availability, population density, power imbalances, and climatic stressors. The proposed model was used to map at high spatial resolution the probability of experiencing hydro-political interactions worldwide. This baseline outline is then compared to four distinct climate and population density projections aimed to estimate trends for hydro-political interactions under future conditions (2050 and 2100), while considering two greenhouse gases emission scenarios (moderate and extreme climate change). The combination of climate and population growth dynamics is expected to impact negatively on the overall hydro-political risk by increasing the likelihood of water interactions in the transboundary river basins, with an average increase ranging between 74.9% (2050 - population and moderate climate change) to 95% (2100 - population and extreme climate change). Future demographic and climatic conditions are expected to exert particular pressure on already water stressed basins such as the Nile, the Ganges/Brahmaputra, the Indus, the Tigris/Euphrates, and the Colorado. The results of this work allow us to identify current and future areas where water issues are more likely to arise, and where cooperation over water should be actively pursued to avoid possible tensions especially under changing environmental conditions. From a policy perspective, the index presented in this study can be used to provide a sound quantitative basis to the assessment of the Sustainable Development Goal 6, Target 6.5 "Water resources management", and in particular to indicator 6.5.2 "Transboundary cooperation".