Age-appropriate vaccination coverage and its determinants in children aged 12-36 months in Nepal: a national and subnational assessment.

BACKGROUND: Vaccination is one of the effective ways to develop immunity against potential life-threatening diseases in children in early age. This study is focused on analysing the age-appropriate vaccination coverage at national and subnational levels and identify the factors associated with age-appropriate coverage in Nepal. METHODS: 460 children aged 12-36 months were included in the study. The data was obtained from Nepal Demographic and Health Survey (NDHS) 2016-17. Age-appropriate coverage of Bacillus Calmette-Guerin vaccine (BCG), oral polio vaccine (OPV) doses 1-3, pentavalent vaccine (PE) doses 1-3, and first dose of measles, mumps, and rubella vaccine (MMR) were estimated using Kaplan Meier method. Multilevel logistic regression with random intercept was used to identify the factors associated with age-appropriate vaccination. RESULTS: The crude coverage of the vaccines included in the study ranged from 91.5% (95% CI, 88.5-93.7) for PE3 to 97.8% (95.8-98.7) for BCG. Although the crude coverage of all the vaccines was above 90%, the age-appropriate coverage was significantly low, ranging from 41.5% (36.5-46.6) for PE3 to 73.9% (69.2-78.1) for PE1. Furthermore, high disparity in timely vaccination coverage was observed at regional level. Compared to the age-appropriate vaccination coverage in other provinces, Province 2 had the lowest coverage of all, followed by that in Province 6. The timeliness of vaccination was significantly associated with subnational regions i.e., provinces and the season of childbirth. CONCLUSION: Although the immunization program in Nepal has achieved the target of 90% crude coverage of all the childhood vaccines, the age-appropriate coverage is significantly low which undermines the effectiveness of the vaccines administered. Thus, along with crude coverage, timeliness of the vaccines administered should be taken into consideration and thoroughly monitored at national and subnational levels. Provincial government should formulate tailored strategies to ensure the timely administration of the childhood vaccines.

The impact of R&D and innovation on global supply chain transition: GTAP analysis on Japan's public R&D investment.

Policymaking for science, technology, and innovation (R&D) is stepping into a new era in the twenty-first century within a highly integrated production network, making it more challenging to capture the impact of R&D investment from an evidence-based approach. To unfold the paradox of the R&D spillover effect spared in the global supply chain, we use computable general equilibrium model with the GTAP database v10 to analyze the impact of Japan's public R&D investment to the world focus on key sectors of global supply chain, namely chemical and pharmaceutical, electronic equipment, machinery, and transportation equipment to examine its output, external trades, and welfare. The productivity parameters triggered by public R&D investment are calibrated from the SciREX Policymaking Intelligent Assistance System-Economic Simulator (SPIAS-e). The simulation results show significant increase in Japan's output and export for chemical and pharmaceutical, electronic equipment, and transportation equipment. The GDP growth was stimulated by 0.6% and substantial welfare improvement by USD 78,000 million, while other countries such as Malaysia and Taiwan by 0.4-0.6%. In contrast, the economic indicators of China reveal a negative impact, implying a structural change in the composition of the production network. It is notable to see a higher economic integration of Oceania within the region through its vibrant production and trades. The study provides comprehensive global analysis on production networks and insights for evaluating the R&D investment spillover effects.

Assessing Factors Associated with TB Awareness in Nepal: A National and Subnational Study.

Tuberculosis (TB) has still remained a serious global health threat in low- and middle-income countries in recent years. As of 2021, Nepal is one of the high TB burden countries, with an increasing prevalence of cases. This study evaluates factors associated with TB awareness in Nepal. This study uses data from the Nepal Demographic and Health Survey, a cross-sectional survey carried out from June 2016 to January 2017. Multilevel logistic regression is performed to examine the association of demographic and socioeconomic factors with TB awareness. Our findings show a high level of TB awareness in all seven provinces of Nepal. Province 5 has the highest level of awareness (98.1%) among all provinces, followed by provinces 3 and 4, while province 6 has the lowest awareness level (93.2%) compared to others. Socioeconomic factors such as wealth, education and owning a mobile phone are significantly associated with TB awareness. Socioeconomic determinants are influential factors associated with TB awareness in Nepal. The wide variation in the proportion of awareness at a regional level emphasizes the importance of formulating tailored strategies to increase TB awareness. For instance, the use of mobile phones could be an effective strategy to promote TB awareness at a regional level. This study provides valuable evidence to support further research on the contribution of information and communication technology (ICT) usage to improving TB awareness in Nepal.

The physiological and behavioral effects of subchronic intracisternal administration of TGF-beta in rats: comparison with the effects of CRF.

We studied the physiological and behavioral effects of subchronic intracisternal administration of transforming growth factor-beta (TGF-beta) for 7 days. Subchronic intracisternal administration of TGF-beta significantly inhibited the increase in body weight of rats but did not affect food intake. In the measurement of locomotor activity after the final intracisternal administration on day 7, the total count for 1.5 h increased significantly in the TGF-beta group compared with the vehicle group. However, that for 10 h was not different between both groups. Furthermore, significant elevations in oxygen consumption were observed in the TGF-beta group during both light and dark phase. Subchronic TGF-beta treatment induced a significant decrease in the number of total leukocytes and lymphocytes and the relative weight of the thymus, and a significant increase in brown adipose tissue weight. Corticotropin-releasing factor (CRF) is the primary neuroendocrine factor released in response to stress. Subchronic treatment with CRF, as a positive control, significantly affected body weight, food intake, oxygen consumption, total leukocyte and lymphocyte counts, and thymus and adrenal weight. Subchronic TGF-beta administration partially mimicked the stress responses, implicating a role for TGF-beta in the brain in stress.

Simian TT virus (s-TTV) infection in patients with liver diseases.

Recently, we identified TTV isolates from nonhuman primates and named them simian TTV (s-TTV). To investigate the prevalence of s-TTV in humans, we examined sera from healthy individuals and patients with liver diseases in Japan for the presence of s-TTV DNA by PCR assay. s-TTV DNA was determined by nested PCR using s-TTV-specific primers designed from untranslated region of s-TTV genome. s-TTV DNA sequence was detected in three of 200 (1.5%) healthy adults but none of 48 infants without liver disease. On the other hand, s-TTV DNA was detected in 30 of 287 (10.5%) Japanese patients with liver disease. s-TTV coinfection with hepatitis B virus and hepatitis C virus were present in 16.7 and 30% of these patients, respectively, while 53.3% of patients were positive for s-TTV alone. Nucleotide sequence analyses in 20 patients confirmed that these PCR products were derived from s-TTV genome sequences and nearly 85% identical to those of s-TTV prototypes from chimpanzees. Phylogenetic analysis demonstrated that all s-TTV isolates from humans were distinguished clearly from the human TTV isolates. Furthermore, s-TTV in humans was classified into two different genotypes as well as simians. Our results indicate that generally 10.5% of Japanese patients with liver diseases were infected with s-TTV. The routes of s-TTV transmission from animal to human require clarification.

Blood lactate functions as a signal for enhancing fatty acid metabolism during exercise via TGF-ß in the brain.

Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-ß (TGF-ß) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-ß. Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-ß in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-ß to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-ß in the brain.

Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity.

We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.

Transforming growth factor-beta in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats.

We have recently reported that inhibition of transforming growth factor (TGF)-beta in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-beta in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-beta in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-beta in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-beta caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-beta administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-beta signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-beta in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-beta.