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

Energy minimization problem in two-level dissipative quantum control: meridian case

International audienceWe analyze the energy-minimizing problem for a two-level dissipative quantum system described by the Kossakowsky-Lindblad equation. According to the Pontryagin Maximum Principle (PMP), minimizers can be selected among normal and abnormal extremals whose dynamics are classified according to the values of the dissipation parameters. Our aim is to improve our previous analysis concerning 2D solutions in the case where the Hamiltonian dynamics are integrable

Genomic and vaccine preclinical studies reveal a novel mouse-adapted Helicobacter pylori model for the hpEastAsia genotype in Southeast Asia

\ua9 2024 Crown Copyright.Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential. Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance. Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies. Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model. Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model. Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden

Remote monitoring of natural slopes. Insights from the first Terrestrial INSAR campaign In Vietnam

Il presente lavoro, realizzato nell'ambito di un progetto di ricerca finanziato dal Vietnamese Space Science & Technology Program, mostra i primi risultati di una campagna di monitoraggio da remoto della frana di Nam Dan (Vietnam settentrionale) dove, per la prima volta nel Paese, è stata utilizzata la tecnica dell'Interferometria SAR Terrestre (TInSAR). Tale tecnica si basa sull’utilizzo di un sensore radar installato su una piattaforma terrestre che trasmette il segnale nel campo delle microonde (banda Ku) e ne riceve gli echi di ritorno dai target riflettenti. Il sensore utilizzato è costituito da due antenne (una trasmittente e una ricevente) e si muove seguendo una traiettoria lineare lungo un binario. Grazie a questa tecnica è possibile effettuare da remoto il monitoraggio delle deformazioni del terreno, raggiungendo una precisione sub-millimetrica in condizioni ideali (ad es. breve distanza, alta riflettività, etc.). Le attività di monitoraggio sono state condotte nel villaggio di Nam Dan, dove una frana attiva con diverse evidenze geomorfologiche quali scarpate, crepe, contropendenze con ristagni d’acqua, abitazioni e beni pubblici gravemente danneggiati, costituisce una seria minaccia per la popolazione locale. L’area di Nam Dan (22°36'N; 104°29'E) si trova nella parte meridionale del distretto di Xin Man, in prossimità del confine tra Vietnam e Cina. Tale distretto, caratterizzato da un clima monsonico umido subtropicale, si estende su un'area di circa 582 km2ed è caratterizzato da una topografia complessa con catene montuose, pendii terrazzati e valli molto profonde con processi erosivi avanzati. Gli archivi locali riportano che in tale area, dal 2012 al 2016, si sono verificate 967 frane, principalmente durante l'estate in corrispondenza delle piogge monsoniche del sud-ovest. Secondo recenti indagini e osservazioni sul campo, la frana oggetto di studio, verificatasi nel luglio del 2012 in seguito a forti precipitazioni, può classificarsi come uno scivolamento traslativo di detrito e si estende su un'area di circa 12.000 m2 con una profondità media di circa 22,5 metri. Nell'agosto del 2013 la frana ha causato nuovi gravi danni a 5 abitazioni, al mercato comunale e alla strada provinciale n. 178 e rappresenta tutt’oggi un grave pericolo per la popolazione residente. Le attività di monitoraggio sono state effettuate tra agosto e dicembre 2019 attraverso un nuovo interferometro radar denominato Phoenix, che è stato utilizzato in una delle sue prime applicazioni sul campo. Il monitoraggio tramite Interferometria SAR Terrestre ha avuto l’obiettivo di controllare l’evoluzione del versante instabile ed ha portato alla realizzazione di mappe di spostamento e delle relative serie temporali, fornendo informazioni dettagliate sulla localizzazione e sui tassi di deformazione dei processi gravitativi di versante presenti. Sebbene nel periodo monitorato non siano state registrate deformazioni significative, l'utilizzo di questa tecnica di telerilevamento, insieme alla strumentazione a contatto precedentemente installata (inclinometri, piezometri, pluviometri) ed alle indagini sul campo, hanno contribuito a migliorare la conoscenza della frana di Nam Dan e la comprensione del suo cinematismo, con particolare riguardo all'evoluzione temporale delle deformazioni superficiali, anche tenendo conto delle condizioni meteorologiche locali. I risultati ottenuti durante la campagna di monitoraggio, in combinazione con i dati precedentemente acquisiti ed elaborati, confermano che il versante oggetto di studio è caratterizzato da fenomeni di instabilità gravitativa, che possono essere innescati da precipitazioni intense che solitamente avvengono nell’area durante la stagione estiva. In considerazione dei contesti ambientali dell'area, quali le severe condizioni climatiche e le aree impervie da percorrere in assenza di infrastrutture viarie adeguate, è stato posto l'accento sulle attività operative sul campo e sull'individuazione di soluzioni tecnologiche appropriate, che hanno rappresentato aspetti particolarmente sfidanti per il monitoraggio di fenomeni franosi tramite tecniche di telerilevamento.The present work, realized in the framework of a research project funded by the Vietnamese Space Science & Technology Program, shows the first insights of remote monitoring at the Nam Dan landslide (Northern Vietnam). The Terrestrial SAR Interferometry (TInSAR) technique was used for the first time in the Country.The activities were performed in Nam Dan village, where an active landslide with several geomorphological evidences as open cracks and scarps, severely damaged dwellings and public assets, constituting a serious hazard to the local inhabitants. The monitoring activities were carried out between August and December 2019 through a new TInSAR device called Phoenix which it was used for one of its first on-field applications. The Terrestrial SAR was aimed at creating displacement maps and related time series, providing detailed information on the location and deformation rate of the processes under investigation. The use of such a remote sensing technique, coupled with contact instrumentation (inclinometers, piezometers, rain gauge) and field surveys have contributed to improving the knowledge about the Nam Dan landslide and the understanding of its behaviour, with particular regard to the time evolution of deformations

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

First report of generalized face processing difficulties in möbius sequence.

Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the production of that expression. Previous work has tested this theory by examining facial expression recognition in participants with Möbius sequence, a condition characterized by congenital bilateral facial paralysis. However, a mixed pattern of findings has emerged, and it has not yet been tested whether these individuals can imagine facial expressions, a process also hypothesized to be underpinned by proprioceptive feedback from the face. We investigated this issue by examining expression recognition and imagery in six participants with Möbius sequence, and also carried out tests assessing facial identity and object recognition, as well as basic visual processing. While five of the six participants presented with expression recognition impairments, only one was impaired at the imagery of facial expressions. Further, five participants presented with other difficulties in the recognition of facial identity or objects, or in lower-level visual processing. We discuss the implications of our findings for the reverse simulation model, and suggest that facial identity recognition impairments may be more severe in the condition than has previously been noted

Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis : longitudinal study and meta-analysis

Canine visceral leishmaniasis is a vector-borne disease caused by the intracellular parasite Leishmania infantum. It is an important veterinary disease, and dogs are also the main animal reservoir for human infection. The disease is widespread in the Mediterranean area, and parts of Asia and South and Central America, and is potentially fatal in both dogs and humans unless treated. Diagnosis of canine infections requires serological or molecular tests. Detection of infection in dogs is important prior to treatment, and in epidemiological studies and control programmes, and a sensitive and specific rapid diagnostic test would be very useful. Rapid diagnostic tests (RDTs) have been developed, but their diagnostic performance has been reported to be variable. We evaluated the sensitivity of a RDT based on serological detection of the rK39 antigen in a cohort of naturally infected Brazilian dogs. The sensitivity of the test to detect infection was relatively low, but increased with time since infection and the severity of infection. We then carried out a meta-analysis of published studies of rK39 RDTs, evaluating the sensitivity to detect disease and infection. The results suggest that rK39 RDTs may be useful in a veterinary clinical setting, but the sensitivity to detect infection is too low for operational control programmes