Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains.

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia. P-BdECM composition is comparable to human BdECM regarding brain-specificity through the matrisome and gene ontology-biological process analysis. As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM. Annexin A1(ANXA1) and Peroxiredoxin(PRDX) in P-BdECM stabilized microglial and astrocytic behavior under normal while promoting active neuroinflammation in response to neuropathological factors. Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study.

Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration.

Neuroinflammation has either beneficial or detrimental effects, depending on risk factors and neuron-glia interactions in neurological disorders. However, studying neuroinflammation has been challenging due to the complexity of cell-cell interactions and lack of physio-pathologically relevant neuroinflammatory models. Here, we describe our three-dimensional microfluidic multicellular human neural culture model, referred to as a 'brain-on-a-chip' (BoC). This elucidates neuron-glia interactions in a controlled manner and recapitulates pathological signatures of the major neurological disorders: dementia, brain tumor and brain edema. This platform includes a chemotaxis module offering a week-long, stable chemo-gradient compared with the few hours in other chemotaxis models. Additionally, compared with conventional brain models cultured with mixed phenotypes of microglia, our BoC can separate the disease-associated microglia out of heterogeneous population and allow selective neuro-glial engagement in three dimensions. This provides benefits of interpreting the neuro-glia interactions while revealing that the prominent activation of innate immune cells is the risk factor leading to synaptic impairment and neuronal loss, validated in our BoC models of disorders. This protocol describes how to fabricate and implement our human BoC, manipulate in real time and perform end-point analyses. It takes 2 d to set up the device and cell preparations, 1-9 weeks to develop brain models under disease conditions and 2-3 d to carry out analyses. This protocol requires at least 1 month training for researchers with basic molecular biology techniques. Taken together, our human BoCs serve as reliable and valuable platforms to investigate pathological mechanisms involving neuroinflammation and to assess therapeutic strategies modulating neuroinflammation in neurological disorders.

Mental Health, Loneliness, and Social Support Among Undergraduate Students: A Multinational Study in Asia.

In this study, we aimed to investigate the prevalence of poor mental health and its association with loneliness and social support among 3531 undergraduate students in nine Asian countries. Mental health was assessed using the Self-Reporting Questionnaire, which was developed by the World Health Organization. Across the entire sample, we detected that nearly half of the students reported poor mental health according to the Self-Reporting Questionnaire and nearly one out of seven students felt lonely. While feeling lonely increased the odds of experiencing poor mental health (odds ratio [OR]), moderate (OR: 0.35) and strong social support (OR: 0.18) decreases the odds of experiencing poor mental health. The high prevalence of poor mental health calls for further in-depth investigations and implementation of mental health support interventions.

In Vitro Tumor Models on Chip and Integrated Microphysiological Analysis Platform (MAP) for Life Sciences and High-Throughput Drug Screening.

The evolution of preclinical in vitro cancer models has led to the emergence of human cancer-on-chip or microphysiological analysis platforms (MAPs). Although it has numerous advantages compared to other models, cancer-on-chip technology still faces several challenges such as the complexity of the tumor microenvironment and integrating multiple organs to be widely accepted in cancer research and therapeutics. In this review, we highlight the advancements in cancer-on-chip technology in recapitulating the vital biological features of various cancer types and their applications in life sciences and high-throughput drug screening. We present advances in reconstituting the tumor microenvironment and modeling cancer stages in breast, brain, and other types of cancer. We also discuss the relevance of MAPs in cancer modeling and precision medicine such as effect of flow on cancer growth and the short culture period compared to clinics. The advanced MAPs provide high-throughput platforms with integrated biosensors to monitor real-time cellular responses applied in drug development. We envision that the integrated cancer MAPs has a promising future with regard to cancer research, including cancer biology, drug discovery, and personalized medicine.

Case report: PICC line for a toddler with bilateral bidirectional Glenn shunt, Fontan circulation, and persistent left superior vena cava.

Performing peripherally inserted central catheters for children with bilateral bidirectional Glenn shunt, Fontan circulation, and persistent left superior vena cava differs from those with normal central venous anatomy. This study presents two PICC procedures for a toddler with this condition to demonstrate an accurate PICC approach for such children.

Effectiveness of digital mental health interventions for university students: an umbrella review.

Background: Poor mental health among university students remains a pressing public health issue. Over the past few years, digital health interventions have been developed and considered promising in increasing psychological wellbeing among university students. Therefore, this umbrella review aims to synthesize evidence on digital health interventions targeting university students and to evaluate their effectiveness. Methods: A systematic literature search was performed in April 2021 searching PubMed, Psychology and Behavioural Science Collection, Web of Science, ERIC, and Scopus for systematic reviews and meta-analyses on digital mental health interventions targeting university students. The review protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO [CRD42021234773]. Results: The initital literature search resulted in 806 records of which seven remained after duplicates were removed and evaluated against the inclusion criteria. Effectiveness was reported and categorized into the following six delivery types: (a) web-based, online/computer-delivered interventions (b) computer-based Cognitive Behavior Therapy (CBT), (c) mobile applications and short message service (d) virtual reality interventions (e) skills training (f) relaxation and exposure-based therapy. Results indicated web-based online/computer delivered-interventions were effective or at least partially effective at decressing depression, anxiety, stress and eating disorder symptoms. This was similar for skills-training interventions, CBT-based intervention and mobile applications. However, digital mental health interventions using virtual reality and relaxation, exposure-based therapy was inconclusive. Due to the variation in study settings and inconsistencies in reporting, effectiveness was greatly dependent on the delivery format, targeted mental health problem and targeted purpose group. Conclusion: The findings provide evidence for the beneficial effect of digital mental health interventions for university students. However, this review calls for a more systematic approach in testing and reporting the effectiveness of digital mental health interventions.

Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis.

BACKGROUND: Degranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue. METHODS: We searched for relevant studies in 10 databases on 15 August 2016. Meta-analysis (MA) was conducted by R version 3.5.0. RESULTS: We included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], -0.348-0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3-0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD -6.531; 95% CI, -12.2 to -0.9). CONCLUSION: VEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.

The role of primary lymph node sites in survival and mortality prediction in Hodgkin lymphoma: a SEER population-based retrospective study.

As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.

Association of psychosis with antiphospholipid antibody syndrome: A systematic review of clinical studies.

OBJECTIVE: In this systematic review, we reviewed the association between Antiphospholipid antibody syndrome (APS) and psychosis and focused on the prevalence, clinical presentation, immunologic and neurological workup, treatment options, and clinical outcomes. METHODOLOGY: We performed this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)'s guidelines. We searched eight databases for potential articles and manually searched references and relevant articles of included studies. We included all articles reporting psychotic symptoms in patients with APS. Article quality was assessed using an adapted version of the Cancer Council Australia tool for case-series. RESULTS: We included 23 articles of 454 articles found. The mean patient age at presentation was 39years and most patients were women. Delusions and hallucinations were the common clinical manifestations of APS-associated psychosis. Findings on neuroimaging were attributed to APS-associated thrombosis in most cases. Most patients had a complete resolution of psychotic symptoms. CONCLUSION: APS-associated psychosis is rare. Later age of onset for psychosis, sudden onset, female sex, and comorbid medical and psychiatric symptoms should raise the suspicions for the presence of APS. APS-associated psychosis may have a favorable prognosis. However, further studies need to validate this conclusion.

Medicinal plants for in vitro antiplasmodial activities: A systematic review of literature.

The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and their active compounds are the most promising source the new antimalarial agents. This study aimed to identify the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentration (IC50)≤1µg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and data extraction were performed by two independent reviewers. The herbs were categorized as very good, good, moderate and inactive if the IC50 values were <0.1µg/ml, 0.1-1µg/ml, >1-5µg/ml and >5µg/ml respectively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive. Among plants identified as having very good to good antiplasmodial crude extracts are Harungana madagascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma desmanthum, and Artemisia annua were reported to have individual compound isolates with very good antiplasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant genera needs to be designed.