Genetic landscape of autism spectrum disorder in Vietnamese children

Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children

A Multidomain Intervention Program for Older People with Dementia: A Pilot Study

Background: Multidomain interventions have been shown to be effective in improving cognition, quality of life, reducing neuropsychiatric symptoms and delaying progression of functional impairment or disability in dementia patients. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, this pilot study will assess the feasibility of a multidomain intervention for older people with dementia in nursing homes in Vietnam. Methods: Participants will be randomized into two equal groups, to receive either a multidomain intervention (intervention group) or regular health advice (control group). The intervention will include physical, cognitive, and social interventions as well as management of metabolic and vascular risk factors. We will hypothesize that the multidomain intervention will be feasible in Vietnam, and participants who receive the intervention will show improvement in quality of life, behaviors, functional ability, cognitive function, sleep, and in reduction of falls, use of healthcare services, and death rate compared to those in the control group during the 6 months intervention period and after the 6 months extended follow-up. Discussion: This is the first study to evaluate the feasibility of a multidomain intervention program for older people with dementia in nursing homes in Vietnam. The results from the trial will inform clinicians and the public of the possibility of comprehensive treatment beyond simply drug treatments for dementia. This paves the way for further studies to evaluate the long-term effects of multidomain interventions in dementia patients. Furthermore, the research results will provide information on the effectiveness of multidomain interventions which will inform policy development on dementia. Trial Registration: The trial is registered with ClinicalTrials.gov identifier: NCT04948450 on 02/07/2021

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio

Combining flowform cascade with constructed wetland to enhance domestic wastewater treatment

This study reports the performance of a new combined flowform cascade (FC) and constructed wetland (CW) system to enhance nitrogen removal and biological degradation of urban wastewater. A series of 8 FC units at the flow rate of 200 L/h could markedly increase the dissolved oxygen level in the wastewater from the initial value of 0.2 mg/L to 5.6 mg/L, thus providing suitable aerobic condition in the front zone of the CW for nitrification and biodegradation of organic contaminants. The results demonstrate that the combined FC/CW system could achieve the sequence of aerobic and anoxic conditions for nitrification and denitrification, respectively. By using a series of FC units for aeration, the CW system could enhance the removal of total nitrogen from 49.4% to 71.2% and biochemical oxygen demand from 80.9% to 86.1% when the hydraulic loading rate was 31.25 m3/m2⋅day. On the other hand, the FC units exerted negligible effects on the phosphate and total suspended solid removals of the CW system. Thus, the combined FC/CW process exhibited phosphate and total suspended solid removals comparable to those of the CW alone

Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study.

BACKGROUND: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. METHODS: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. FINDINGS: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). CONCLUSION: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies