Prevalence of autism spectrum disorder among children in Southeast Asia from 2002 to 2022: An updated systematic review and meta-analysis.

Background and Aims: Autism spectrum disorder (ASD) is a neurodevelopmental condition that impacts the brain, characterized by challenges in social communication and interaction, often accompanied by repetitive behaviors or focused interests. This study sheds light on the prevalence of ASD within the Southeast Asian region. Methods: The study protocol was registered in PROSPERO (Registration No: CRD42023413915). Appropriate search terms and Boolean operators were employed to explore electronic databases for relevant articles. Data thus extracted were prepared in Excel and analyzed in Comprehensive Meta-Analysis Software. The effect measure utilized in the study was represented by the proportion, and the choice between a fixed or random-effect model depended on the observed heterogeneity. Visual feedback was provided through the use of forest plots and funnel plots. Results: A total of 14 studies were included in the qualitative and quantitative synthesis after screening the imported studies. The prevalence of ASD was six per 1000 population (proportion: 0.006; CI: 0.002-0.017; I 2: 99.263%). Among the ASD cases, 64.4% (proportion: 0.644; CI: 0.590-0.693; I 2: 9.937%) were males and 35.6% (proportion: 0.356; CI: 0.307-0.410; I 2: 9.937%) were females. Conclusion: The prevalence of ASD in Southeast Asia was estimated to be six cases per 1000 individuals, with a higher prevalence among males. This study contributes to our understanding of ASD prevalence in the region, although it is essential to note certain limitations in estimating prevalence.

Perceived caregiver's burden among children with autism spectrum disorder in central Nepal: a cross-sectional study.

Autism spectrum disorder (ASD) is the most common childhood neurodevelopmental disorder characterized by an atypical social and communicative functioning and restricted, repetitive patterns of behaviour activities. Caring for children with ASD is challenging for both parents and their caregivers. This study aims to explore the psychosocial burden of the caregivers of children with ASD. Materials and methodology: An analytical cross-sectional study was performed in Centre for Autism in Kathmandu, Nepal. The enrolment occurred between January 2022 and July 2022 among the caregivers of children with ASD. One hundred twenty caregivers in contact with the centre was evaluated using the Zarit Burden Interview-22 during the study period meeting inclusion criteria. Results: Our study showed that majority of caregivers among child with ASD were mothers 65 (54.16%, n=65) followed by grandparents 35 (29.16%, n=35) and father 13 (10.8%), respectively. Among them, most of the caregivers perceived moderate to severe burden 57 (47.5%) followed by mild to moderate burden 45 (37.5%) and only 7 (5.8%) of the caregivers perceived severe burden during the study which was found to be statistically significant. Conclusions: This study highlighted the fact that although most of the caregivers perceived moderate to severe burden while caring a child with ASD. The degree of burden significantly correlated with the level of ASD in the child.

Scalable and Uniform Fabrication of Dexamethasone-Eluting Depot-Engineered Stem Cell Spheroids as a Microtissue Construct to Target Bone Regeneration.

Potentiation of stem cell potency is critical for successful tissue engineering, especially for bone regeneration. Three-dimensional cell culture and bioactive molecule co-delivery with cells have been proposed to achieve this effect. Here, we provide a uniform and scalable fabrication of osteogenic microtissue constructs of mesenchymal stem cell (MSC) spheroids surface-engineered with dexamethasone-releasing polydopamine-coated microparticles (PD-DEXA/MPs) to target bone regeneration. The microparticle conjugation process was rapid and cell-friendly and did not affect the cell viability or key functionalities. The incorporation of DEXA in the conjugated system significantly enhanced the osteogenic differentiation of MSC spheroids, as evidenced by upregulating osteogenic gene expression and intense alkaline phosphatase and alizarin red S staining. In addition, the migration of MSCs from spheroids was tested on a biocompatible macroporous fibrin scaffold (MFS). The result showed that PD-DEXA/MPs were stably anchored on MSCs during cell migration over time. Finally, the implantation of PD-DEXA/MP-conjugated spheroid-loaded MFS into a calvarial defect in a mouse model showed substantial bone regeneration. In conclusion, the uniform fabrication of microtissue constructs containing MSC spheroids with drug depots shows a potential to improve the performance of MSCs in tissue engineering.

Complicated pylephlebitis secondary to perforated appendicitis in a child- A rare case report.

Introduction and importance: Pylephlebitis is a rare and life threatening thrombophlebitis of the portal vein. It commonly occurs following intra abdominal infections like appendicitis.It is even rarer in the pediatric age group. The nonspecific presentation impedes the diagnosis. Timely use of appropriate antibiotics and control of infection is paramount in its treatment and this case report highlights the same. Case presentation: 11 year old female child from a rural area was referred from a local hospital for persistent fever and abdominal pain despite medical treatment. Workup revealed perforated appendicitis, pylephlebitis, and multiple liver abscess. She was successfully treated with appendicectomy followed by antibiotics and anticoagulants. Clinical discussion: Pylephlebitis secondary to appendicitis was frequently lethal in the pre-antibiotic era. Doppler ultrasonography and CT scan are the investigations of choice to establish the diagnosis by showing a thrombus in the portal vein. With use of antibiotics, early diagnosis by imaging and surgical control of the primary infection, appendicitis-associated-pylephlebitis now has improved outcomes. Larger scale studies are required to establish the role of anticoagulants. Conclusion: Early diagnosis and intervention of this fatal condition is life saving but numerous gaps exist in the literature regarding the treatment recommendation.

Acute recurrent pancreatitis in a child with pancreatic divisum- A case report.

Introduction and importance: In children, acute recurrent pancreatitis is attributed to pancreato-biliary anomalies, hereditary pancreatitis and cystic fibrosis. Pancreatic divisum is a common congenital ductal anomaly that leads to recurrence of pancreatitis. Case presentation: A 13 years old female presented with clinical features of acute recurrent pancreatitis. After ruling out common causes, magnetic resonance cholangiopancreatography was done which showed pancreatic divisum. Her symptoms resolved following duodenum preserving pancreatic head resection. Discussion: Acute recurrent pancreatitis is attributed to raised intrapancreatic dorsal ductal pressure due to ductal anomalies especially pancreatic divisum (PD). It is the embryological failure in the fusion of the dorsal and ventral ductal system. PD is further classified into a classical subtype where there is complete failure of ductal fusion and an incomplete subtype where there is partial fusion of the ductal system. The diagnosis is commonly done through abdominal imaging with secretin enhanced magnetic resonance cholangiopancreatography being the choice of imaging modality. The initial approach is endoscopic intervention unless patients present with signs of pancreatic fibrosis where a duodenum preserving pancreatic head resection can be carried out. Conclusion: A keen suspicion should be given towards anatomical or structural variants in absence of common etiologies. Early identification and management of pancreatic divisum prevents the recurrence of pancreatitis.

Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets.

Pancreatic islet transplantation holds great potential as a curative therapy for treating type 1 diabetes. However, the need for lifelong systemic immunosuppression with inevitable side effects is an obstacle to clinical success. Here we devised a strategy for the site-specific delivery of an immunosuppressant (tacrolimus) using layer-by-layer assembly of polymeric particles and collagen on the islet surface. This approach aims to provide a continuous and sustained supply of tacrolimus in the vicinity of transplanted cells while avoiding systemic drug exposure. The dose and release rate of tacrolimus can be tunable to achieve therapeutic windows by varying layer-by-layer construction and chemistry of polymers. Transplanting 400 IEQ of pancreatic islets coated with particles containing ∼3 µg of TAC per recipient provided controlled drug release and rectified diabetes for up to 5 months in a xenogeneic rodent model of type 1 diabetes. We anticipate that the findings of this study will be found useful by those developing local immunomodulation strategies aimed at improving the outcomes and safety of cell therapies for curing type 1 diabetes.

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic-co-glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incubating cell-particle mixture in methylcellulose solution while maintaining high cell viability. RAP-MPs were uniformly distributed in hybrid spheroids and sustainably released RAP for ~3 weeks. Locoregional transplantation of hybrid spheroids containing low doses of RAP-MPs (200- to 4000-ng RAP per recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced programmed death-ligand 1 expression by MSCs was found to be responsible for the immunomodulatory performance of hybrid spheroids. Our results suggest that these hybrid spheroids offer a promising platform for the efficient use of MSCs in the transplantation field.

Immunomodulation effect of mesenchymal stem cells in islet transplantation.

Mesenchymal stem cells (MSCs) therapy has brought a great enthusiasm to the treatment of various immune disorders, tissue regeneration and transplantation therapy. MSCs are being extensively investigated for their immunomodulatory actions. MSCs can deliver immunomodulatory signals to inhibit allogeneic T cell immune responses by downregulating pro-inflammatory cytokines and increasing regulatory cytokines and growth factors. Islet transplantation is a therapeutic alternative to the insulin therapy for the treatment of type 1 diabetes mellitus (T1DM). However, the acute loss of islets due to the lack of vasculature and hypoxic milieu in the immediate post-transplantation period may lead to treatment failure. Moreover, despite the use of potent immunosuppressive drugs, graft failure persists because of immunological rejection. Many in vitro and in vivo researches have demonstrated the multipotency of MSCs as a mediator of immunomodulation and a great approach for enhancement of islet engraftment. MSCs can interact with immune cells of the innate and adaptive immune systems via direct cell-cell contact or through secretomes containing numerous soluble growth and immunomodulatory factors or mitochondrial transfer. This review highlights the interactions between MSCs and different immune cells to mediate immunomodulatory functions along with the importance of MSCs therapy for the successful islet transplantation.