Functional difficulty among young children in Bangladesh: An analysis of nationally representative data.

Functional difficulty in children is a crucial public health problem still undervalued in developing countries. This study explored the socio-demographic factors and anthropometry associated with children's functional difficulty in Bangladesh. Data for 2-4-year-old children, obtained from Multiple Indicator Cluster Survey 2019, were used in this study. The mixed-effects logistic regression model was used to analyse the data. Children whose mothers had functional difficulty were found to be 2.75 times more likely to have functional difficulty than children whose mothers had no functional difficulty (95% CI 1.63-4.63). Male children were more likely to experience functional difficulty than female children (OR = 1.48). Furthermore, stunting was found to be significantly associated with functional difficulty (OR = 1.50). The study also revealed that division and mother's education, specifically, children with mothers having higher secondary + education, had significant association with the outcome variable. The findings provided a vital overview of child disability in a developing country.

Future prospects of MXenes: synthesis, functionalization, properties, and application in field effect transistors.

MXenes are a family of two-dimensional (2D) materials that have drawn a lot of interest recently because of their distinctive characteristics and possible uses in a variety of industries. This review emphasizes the bright future prospects of MXene materials in the realm of FETs. Their remarkable properties, coupled with their tunability and compatibility, position MXenes as promising candidates for the development of high-performance electronic devices. As research in this field continues to evolve, the potential of MXenes to drive innovation in electronics becomes increasingly evident, fostering excitement for their role in shaping the future of electronic technology. This paper presents a comprehensive overview of MXene materials, focusing on their synthesis methods, functionalization strategies, intrinsic properties, and their promising application in Field Effect Transistors (FETs).

Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion.

During neural development, cellular adhesion is crucial for interactions among and between neurons and surrounding tissues. This function is mediated by conserved cell adhesion molecules, which are tightly regulated to allow for coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates the Menorin adhesion complex during development of PVD dendritic arbors in Caenorhabditis elegans. We found a finely regulated antagonistic balance between PVD-expressed KPC-1 and the epidermally expressed putative cell adhesion molecule MNR-1 (Menorin). Genetically, partial loss of mnr-1 suppressed partial loss of kpc-1, and both loss of kpc-1 and transgenic overexpression of mnr-1 resulted in indistinguishable phenotypes in PVD dendrites. This balance regulated cell-surface localization of the DMA-1 leucine-rich transmembrane receptor in PVD neurons. Lastly, kpc-1 mutants showed increased amounts of MNR-1 and decreased amounts of muscle-derived LECT-2 (Chondromodulin II), which is also part of the Menorin adhesion complex. These observations suggest that KPC-1 in PVD neurons directly or indirectly controls the abundance of proteins of the Menorin adhesion complex from adjacent tissues, thereby providing negative feedback from the dendrite to the instructive cues of surrounding tissues.

Side effects of COVID-19 vaccines and perceptions about COVID-19 and its vaccines in Bangladesh: A Cross-sectional study.

Objective: One of the primary reasons for hesitancy in taking COVID-19 vaccines is the fear of side effects. This study primarily aimed to inspect the potential side effects of the COVID-19 vaccines circulated in Bangladesh.Design and Settings.The study was based on a cross-sectional anonymous online survey conducted in December 2021 across Bangladesh.Participants.The study included consenting Bangladeshi individuals aged 12 and above who had received at least one dose of the COVID-19 vaccines.Main Outcome.Analyses were carried out through exploratory analysis, Chi-square test, and logistic regression to investigate potential side effects of the COVID-19 vaccines. Results: A total of 1,180 vaccinated people participated in the study. Only 39.48% of the participants reported at least one side effect after receiving their COVID-19 vaccine. Injection-site pain, fever, headache, redness/swelling at the injection site, and lethargy were the most commonly reported adverse effects, all of which were mild and lasted 1-3 days. Side effects were most prevalent (about 80%) among individuals who received Pfizer-BioNTech and Moderna vaccines and were least common among those who received Sinopharm and Sinovac vaccines (21%-28%). When compared to the Sinopharm vaccines, the OxfordAstraZeneca, Pfizer-BioNTech, and Moderna vaccines were 4.51 times (95% CI: 2.53-8.04), 5.37 times (95% CI: 2.57-11.22), and 4.28 times (95% CI: 2.28-8.05) likelier to produce side effects. Furthermore, males, those over 50 years old, urban dwellers, smokers, and those with underlying health issues had a considerably increased risk of developing side effects. A lack of confidence in vaccines' efficacy and a substantial level of hesitancy in allowing children (age five years or over) and older people (70 years or over) to receive COVID-19 vaccines were also observed. Conclusion: Side effects of COVID-19 vaccines are minimal, demonstrating their safety. Efforts should be made to disseminate such findings worldwide to increase vaccine uptake.

Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning.

N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning.

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.

The costs of disability in Australia: a hybrid panel-data examination.

BACKGROUND: Over four million people in Australia have some form of disability, of whom 2.1 million are of working age. This paper estimates the costs of disability in Australia using the standard-of-living approach. This approach defines the cost of disability as additional income required for people with a disability to achieve a similar living standard to those without a disability. We analyse data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey using a hybrid panel data model. To the best of our knowledge, this is the first study to examine the costs of disability in Australia using a high quality, large, nationally-representative longitudinal data set. METHODS: This study estimates the costs of disability in Australia by using the Standard of Living (SoL) and a dynamic model approach. It examines the dynamics of disability and income by using lagged disability and income status. The study also controls for unobserved individual heterogeneity and endogeneity of income. The longitudinal specification in this study allows us to separate short- and long-run costs of disability using a hybrid panel data regression approach. RESULTS: Our results show that people with a disability need to increase their adult-equivalent disposable income by 50% (in the short-run) to achieve the same standard of living as those without a disability. This figure varies considerably according to the severity of the disability, ranging from 19% for people without work-related limitations to 102% for people with severe limitations. Further, the average cost of disability in the long-run is higher and it is 63% of the adult-equivalent disposable income. CONCLUSIONS: Firstly, our results show that with the same level of income, the living standard is lower in households with people with a disability compared to households without members with a disability. This indicates a strong relationship between poverty and disability. However, current poverty measures do not take into account disability, therefore, they fail to consider substantial differences in poverty rates between people with and without a disability. Secondly, the estimated costs reflected in this study do consider foregone income due to disability. Therefore, policymakers should seriously consider adopting disability-adjusted poverty and inequality measurements. Thirdly, increasing the income (e.g. through government payments) or providing subsidised services for people with a disability may increase their financial satisfaction, leading to an improved living standard. The results of this study can serve as a baseline for the evaluation of the National Disability Insurance Scheme (NDIS).

The income gradient and child mental health in Australia: does it vary by assessors?

In this paper, we examine the income gradient in child mental health using longitudinal data from a large, national cohort of Australian children. We contribute to the body of existing literature by: (i) investigating whether and to what extent a child's mental health levels and their relationship to income vary when a child's mental health is assessed by the child's parent, the child's teacher and the child her/himself; (ii) exploring whether the reporting differences in a child's mental health is associated systematically with household income; and (iii) examining the child mental health gradient and the evolution of this gradient by the child's age. We found that a child's mental health and the income gradient vary depending on who assesses the child's mental health (the gradient was the largest when assessed by parents and the smallest when assessed by the child). Furthermore, the magnitude of the effect of mental health and income gradient faded when we controlled for some important variables, such as maternal health.

TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization.

Dendritic arbors are crucial for nervous system assembly, but the intracellular mechanisms that govern their assembly remain incompletely understood. Here, we show that the dendrites of PVD neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine-rich transmembrane (LRR-TM) receptor. DMA-1/LRR-TM interacts through a PDZ ligand motif with the guanine nucleotide exchange factor TIAM-1/GEF in a complex with act-4/Actin to pattern higher order 4° dendrite branches by localizing F-actin to the distal ends of developing dendrites. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. A partially redundant pathway, dependent on HPO-30/Claudin, regulates formation of 2° and 3° branches, possibly by regulating membrane localization and trafficking of DMA-1/LRR-TM. Collectively, our experiments suggest that HPO-30/Claudin localizes the DMA-1/LRR-TM receptor on PVD dendrites, which in turn can control dendrite patterning by directly modulating F-actin dynamics through TIAM-1/GEF.

Health care expenditure and health outcome nexus: new evidence from the SAARC-ASEAN region.

BACKGROUND: The total health expenditure (as a percentage of GDP) and health outcomes in the region of South Asian Association for Regional Cooperation (SAARC) and Association for South East Asian Nations (ASEAN) are lower than that of the OECD region and the world. This study investigated the relationship between different types of healthcare expenditures (public, private and total) and three main health status outcomes - life expectancy at birth, crude death rate and infant mortality rate - in the region. METHODOLOGY: Using the World Bank data set for 15 countries over a 20-year period (1995-2014), a panel data analysis was conducted where relevant fixed and random effect models were estimated to determine the effects of healthcare expenditure on health outcomes. The main variables studied were total health expenditure, public health expenditure, private health expenditure, GDP per capita, improved sanitation, life expectancy at birth, crude death rate and infant mortality rate. RESULTS: Total health expenditure, public health expenditure and private health expenditure significantly reduced infant mortality rates, and, the extent of effect of private health expenditure was greater than that of public health expenditure. Private health expenditure also had a significant role in reducing the crude death rate. Per capita income growth and improved sanitation facilities also had significant positive roles in improving population health in the region. CONCLUSIONS: Health expenditure in the SAARC-ASEAN region should be increased as our results indicated that it improved the health status of the population in the region. Public sector health funds must be appropriately and efficiently used, and accountability and transparency regarding spending of public health funds should be ensured. Finally, government and private institutes should implement appropriate strategies to improve sanitation facilities.

Muscle- and Skin-Derived Cues Jointly Orchestrate Patterning of Somatosensory Dendrites.

Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1-3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin-SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the leucine-rich transmembrane receptor DMA-1/LRR-TM expressed on PVD neurons [8, 9]. Here we describe a role for the diffusible C. elegans protein LECT-2, which is homologous to vertebrate leukocyte cell-derived chemotaxin 2 (LECT2)/Chondromodulin II. LECT2/Chondromodulin II has been implicated in a variety of pathological conditions [10-13], but the developmental functions of LECT2 have remained elusive. We find that LECT-2/Chondromodulin II is required for development of PVD and FLP dendritic arbors and can act as a diffusible cue from a distance to shape dendritic arbors. Expressed in body-wall muscles, LECT-2 decorates neuronal processes and hypodermal cells in a pattern similar to the cell adhesion molecule SAX-7/L1CAM. LECT-2 functions genetically downstream of the MNR-1/Menorin-SAX-7/L1CAM adhesion complex and upstream of the DMA-1 receptor. LECT-2 localization is dependent on SAX-7/L1CAM, but not on MNR-1/Menorin or DMA-1/LRR-TM, suggesting that LECT-2 functions as part of the skin-derived MNR-1/Menorin-SAX-7/L1CAM adhesion complex. Collectively, our findings suggest that LECT-2/Chondromodulin II acts as a muscle-derived, diffusible cofactor together with a skin-derived cell adhesion complex to orchestrate the molecular interactions of three tissues during patterning of somatosensory dendrites.

O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1.

Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.

Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens.

BACKGROUND: A variety of pain conditions have been found to be associated with depressed mood in clinical studies. Depression-like behaviors have also been described in animal models of persistent or chronic pain. In rodent chronic neuropathic pain models, elevated levels of GluA1 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the nucleus accumbens (NAc) have been found to inhibit depressive symptoms. However, the effect of reversible post-surgical pain or inflammatory pain on affective behaviors such as depression has not been well characterized in animal models. Neither is it known what time frame is required to elicit AMPA receptor subunit changes in the NAc in various pain conditions. RESULTS: In this study, we compared behavioral and biochemical changes in three pain models: the paw incision (PI) model for post-incisional pain, the Complete Freund's Adjuvant (CFA) model for persistent but reversible inflammatory pain, and the spared nerve injury (SNI) model for chronic postoperative neuropathic pain. In all three models, rats developed depressive symptoms that were concurrent with the presentation of sensory allodynia. GluA1 levels at the synapses of the NAc, however, differed in these three models. The level of GluA1 subunits of AMPA-type receptors at NAc synapses was not altered in the PI model. GluA1 levels were elevated in the CFA model after a period (7 d) of persistent pain, leading to the formation of GluA2-lacking AMPA receptors. As pain symptoms began to resolve, however, GluA1 levels returned to baseline. Meanwhile, in the SNI model, in which pain persisted beyond 14 days, GluA1 levels began to rise after pain became persistent and remained elevated. In addition, we found that blocking GluA2-lacking AMPA receptors in the NAc further decreased the depressive symptoms only in persistent pain models. CONCLUSION: Our study shows that while both short-term and persistent pain can trigger depression-like behaviors, GluA1 upregulation in the NAc likely represents a unique adaptive response to minimize depressive symptoms in persistent pain states.