Survey for Caregivers of People with Autism Spectrum in Chile: Access to Health and Education Services, Satisfaction, Quality of Life And Stigma [Encuesta para Cuidadores de Personas del Espectro Autista en Chile. Acceso a Servicios de Salud y Educación, Satisfacción, Calidad de Vida y Estigma]

People on the Autism Spectrum (AS) face multiple health, education, social, and economic problems. There is limited available information in Chile. \ Objective: To describe the access and satisfaction with health and education services, family and economic impact, stigma, and quality of life of people with AS and their families in Chile. Subjects and Method: Parents/caregivers of AS persons completed the Caregiver Needs Survey, developed by Autism Speaks, which includes demographic information, characteristics of AS persons (previously published), use of health and education services, parents/caregivers\u27 perceptions of satisfaction, impact, stigma, and quality of life. Results: 291 caregivers (86% mothers) of 291 AS persons participated, 89% were male, aged 1-40 years (X:10.4 SD:6.1). Limited and unspecific access to health services is reported. 77% are regularly attending a standard or special school system. Families pay for over 60% of therapies/medical care and over 40% of specific educational support, and 25% report difficulties in accessing services. The family income is affected by resignation (35%) or reduced working hours (46%). Stigma is associated with possible discrimination and feelings of helplessness. The main priorities mentioned for a better quality of life are support for inclusive schooling, better adjustment at home, and improved socialization. Conclusions: This survey provides relevant information about the needs, barriers, and challenges of AS people in Chile and highlights the difficulties in accessing health services and the severe impact on family income. Feelings of stigma, discrimination, and helplessness are reported. Collaborative strategies are needed to improve the quality and access to services and to reduce the economic and mental health burden on the family. - Introducción: Las personas del Espectro Autista (EA) enfrentan múltiples necesidades de salud, educación, problemas sociales y económicos. La información disponible en Chile es insuficiente. Objetivo: Conocer el acceso y satisfacción con servicios de salud y educación, el impacto familiar y económico, estigma y calidad de vida de personas EA y sus familias en Chile. Sujetos y Método: Padres/cuidadores de perso nas EA respondieron la Encuesta de Necesidades de Cuidadores, desarrollada por Autism Speaks, que comprende: información demográfica, características de las personas EA (publicado previamente), utilización de servicios de salud y educación, percepciones de padres/cuidadores en satisfacción, im pacto, estigma y calidad de vida (que presenta esta publicación). Resultados: Participaron 291 cuida dores (86% madres), de 291 personas EA, 89% varones, de 1-40 años (X:10,4 DE:6,1). Se reporta un acceso insuficiente y poco específico a servicios de salud. Un 77% asiste regularmente a algún sistema escolar regular o especial. Las familias financian sobre 60% de terapias/atención médica y sobre 40% de apoyos educacionales específicos; un 25% refiere dificultades de acceso a servicios. La economía familiar se afecta por renuncia (35%) o reducción de jornadas laborales de los cuidadores (46%). El estigma se asocia a posible discriminación y sentimientos de impotencia. Las principales prioridades mencionadas para una mejor calidad de vida son apoyos para escolaridad inclusiva, mejor adaptación en el hogar y mejorar la socialización. Conclusiones: Esta encuesta aporta información relevante acerca de las necesidades, barreras y desafíos de las personas EA en Chile. Destacan las dificultades de acceso a servicios de salud y el severo impacto sobre el ingreso económico familiar. Existe estigma, discriminación e impotencia. Se requiere elaborar estrategias colaborativas para mejorar la calidad y acceso a servicios y reducir la carga económica y de salud mental familiar

High Diversity of Giardia duodenalis Assemblages and Sub-Assemblages in Asymptomatic School Children in Ibadan, Nigeria

Giardia duodenalis is a significant contributor to the burden of diarrheal disease in sub-Saharan Africa. This study assesses the occurrence and molecular diversity of G. duodenalis and other intestinal parasites in apparently healthy children (n = 311) in Ibadan, Nigeria. Microscopy was used as a screening method and PCR and Sanger sequencing as confirmatory and genotyping methods, respectively. Haplotype analyses were performed to examine associations between genetic variants and epidemiological variables. At microscopy examination, G. duodenalis was the most prevalent parasite found (29.3%, 91/311; 95% CI: 24.3-34.7), followed by Entamoeba spp. (18.7%, 58/311; 14.5-23.4), Ascaris lumbricoides (1.3%, 4/311; 0.4-3.3), and Taenia sp. (0.3%, 1/311; 0.01-1.8). qPCR confirmed the presence of G. duodenalis in 76.9% (70/91) of the microscopy-positive samples. Of them, 65.9% (60/91) were successfully genotyped. Assemblage B (68.3%, 41/60) was more prevalent than assemblage A (28.3%, 17/60). Mixed A + B infections were identified in two samples (3.3%, 2/60). These facts, together with the absence of animal-adapted assemblages, suggest that human transmission of giardiasis was primarily anthroponotic. Efforts to control G. duodenalis (and other fecal-orally transmitted pathogens) should focus on providing safe drinking water and improving sanitation and personal hygiene practices.This research was funded by the Health Institute Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, grant number PI19CIII/00029.S

A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Background Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs.Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry.Results This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5).Conclusions This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.Trial registrationClinicalTrials.gov Identifier: NCT00628745

Chemoenzymatic synthesis of polypeptides in neat 1,1,1,2-tetrafluoroethane solvent

Chemoenzymatic polypeptide synthesis offers several advantages over chemical or other biological routes, however, the use of aqueous-based media suffers from reverse hydrolysis reactions that challenge peptide chain propagation. Herein, the protease from subtilisin Carlsberg biocatalyzed the synthesis of poly-L-PheOEt, poly-L-LeuOEt, and the copolymers poly-L-PheOEt-co-L-LeuOEt from their amino acid ethyl ester substrates in a neat liquid 1,1,1,2-tetrafluoroethane solvent. The products, achieved in acceptable yields (ca. 50%), were fully characterized showing relatively high molar mass (ca. 20 000 Da for poly-L-PheOEt). This non-toxic low-boiling hydrofluorocarbon enhances enzymatic peptide propagation by limiting hydrolysis owing to its hydrophobic and relatively polar characteristics that sustain the protease activity and solubilize substrates and products. Computational molecular dynamic calculations were used to assess the L-PheOEt/L-LeuOEt-solvent and polypeptide-solvent interactions in this system. Additionally, the homopolypeptides displayed higher crystallinity than the copolypeptides with random incorporation of amino acid ethyl esters, notwithstanding the significantly highest specificity for Phe in this system. Interestingly, secondary structure characterization of the products by FTIR and circular dichroism suggests a non-common peptide folding

Effects of hyperprolactinemia on ornithine decarboxylase activity and polyamine levels in seminal vesicles of genetically prolactin-deficient adult dwarf mice

Prolactin (PRL) has been shown to exert many different actions in various biological systems. Polyamines are known to influence the growth and function of the seminal vesicles (SV). Furthermore, ornithine decarboxylase (ODC) is considered a key enzyme In the biosynthesis of polyamines and Is regulated by PRL in certain target tissues. Adult Ames dwarf mice (df/df), genetically deficient In PRL, were used for this study. The experimental groups were as follows: Group 1, pituitary-grafted; Group 2, sham-operated; Group 3, castrated + testosterone propionate (TP)-treated (25 sag/mouse, 3 times/wk, s.c.) + grafted; and Group 4, castrated + TP as above. The animals were killed 40 days later, and polyamines and ODC activity in SV and liverwere determined. Serum PRL, FSH, and testosterone (T) were also measured. In the grafted groups, there were significant elevations in serum PRL and FSH levels. In the gonad-intact, pituitary-grafted group, animals exhibited an elevation in plasma T levels, and similar levels were achieved in the castrated, androgen-replaced groups. In hyperprolactinemic mice, the weights of SV were significantly greater than in the corresponding control groups. The relative weights of the SV showed a similar pattern. An increase in ODC activity was observed in both SV and liver in hyperprolactinemic groups. In those animals in which senam T levels were held constant, an increase in the enzyme activity in SV was detected in hyperprolactinemic group whereas in liver,no significant difference was observed. Concentrations of polyamines in the SV were increased in hyperprolactinemic, castrated, TP-treated mice. The present results indicate that PRL can exert a direct stimulatory effect on the growth, ODC activity, and polyamine levels in the SV.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias Exacta

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Global testing of a consensus solubility assessment to enhance robustness of the WHO biopharmaceutical classification system

The WHO Biopharmaceutical Classification System (BCS) is a practical tool to identify active pharmaceutical ingredients (APIs) that scientifically qualify for a waiver of in vivo bioequivalence studies. The focus of this study was to engage a global network of laboratories to experimentally quantify the pH-dependent solubility of the highest therapeutic dose of 16 APIs using a harmonized protocol. Intra-laboratory variability was ≤5 %, and no apparent association of inter-laboratory variability with API solubility was discovered. Final classification “low solubility” vs “high solubility” was consistent among laboratories. In comparison to the literature-based provisional 2006 WHO BCS classification, three compounds were re-classified from “high” to “low-solubility”. To estimate the consequences of these experimental solubility results on BCS classification, dose-adjusted in silico predictions of the fraction absorbed in humans were performed using GastroPlus®. Further expansion of these experimental efforts to qualified APIs from the WHO Essential Medicines List is anticipated to empower regulatory authorities across the globe to issue scientifically-supported guidance regarding the necessity of performing in vivo bioequivalence studies. Ultimately, this will improve access to affordable generic products, which is a critical prerequisite to reach Universal Health Coverage

Agrárpiaci Jelentések, Baromfi

Amerikai Egyesült Államok agrárminisztériumának (USDA) májusban megjelent jelentése szerint az USA csirkehústermelése 4,6 millió tonna körül alakult 2017 első negyedévében, ami 2 százalékkal haladta meg az előző év azonos időszakának kibocsátását. Az Európai Bizottság adatai alapján 2017 első 20 hetében 178 euró/100 kilogramm volt az egész csirke uniós átlagára, kismértékben csökkent az előző év hasonló időszakának átlagárához viszonyítva. Magyarországon a vágócsirke élősúlyos termelői ára (245,9 forint/kilogramm) 4,3 százalékkal volt alacsonyabb 2017 20. hetében az egy évvel korábbinál

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS):14-year update

Abstract Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.http://deepblue.lib.umich.edu/bitstream/2027.42/173793/1/13023_2022_Article_2359.pd

The effects of two early parenting interventions on child aggression and risk for violence in Brazil (The PIÁ Trial): protocol for a randomised controlled trial

Background Children in many low- and middle-income countries (LMICs) are at high risk for exposure to violence and later violent behaviour. The World Health Organization has declared an urgent need for the evaluation and implementation of low-cost parenting interventions in LMICs to prevent violence. Two areas of significant early risk are harsh parenting and poor child cognitive and socio-emotional development. Parenting interventions suitable for LMIC contexts have been developed targeting these risk factors and have been shown to have promising effects. However, their impact on child aggression, a key precursor of violence, has yet to be determined. The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) has been designed to address this issue. Methods We are conducting a randomised controlled trial to evaluate two early parenting interventions for mothers of children aged between 30 and 42 months in a Brazilian city. The first of these, dialogic book-sharing (DBS), aims to promote child cognitive and socio-emotional development; and the second, the ACT Raising Safe Kids Program (ACT), is designed to reduce harsh parenting. These interventions are being compared with a control group receiving neither intervention. Three hundred and sixty-nine families in a birth cohort are being randomly allocated to one of the three groups (DBS, ACT, Control). Facilitators deliver the interventions to groups of five to 10 mothers at weekly sessions for 8 weeks in DBS and 9 weeks in ACT. Independent assessments of parenting and child development are being made before the interventions, shortly afterwards, and at follow-up 6 months later. The primary outcome is child aggression, and the two main secondary outcomes are: (1) child cognitive and socio-emotional development and (2) harsh parenting. Longer-term outcomes will be investigated as the birth cohort is followed into late childhood, adolescence, and adulthood. Discussion The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) aims to evaluate the impact of two early parenting interventions on child aggression and several other key risk factors for the development of violence, including aspects of parenting and child cognition and socio-emotional functioning. The study is being carried out in a LMIC context where violence constitutes a major social and health burden. Since the two interventions are brief and, with modest levels of training, readily deliverable in LMIC settings, a demonstration that they benefit parenting and reduce risk factors for violence would be of major significance