The Role of Water, Sanitation and Hygiene (WaSH) Interventions on Health and Behavioral Outcomes during Humanitarian Crisis: A Systematic Review and Meta-Analysis.

Background: In humanitarian crises, water, sanitation and hygiene interventions are critical for the survival of people. However, strong evidence-based information is still limited. In order to describe the quantity and quality of current evidence, we conducted an evidence gap map provides a visual overview, highlighting areas lacking evidence. Methods: According to developed inclusion and exclusion criteria, a systematic literature search was conducted to find related systematic reviews and meta-analyses. The databases, including PubMed, Web of Science, SCOPUS and Cochrane were searched using search strings from 2000 until 2021. Characteristics of the included reviews were extracted and summarized. Two persons evaluated methodological quality independently using the AMSTAR tool. Invite a third person to solve any discrepancies. Results: This study revealed seven systematic reviews, including one meta-analysis. One study was of high quality, four of medium, and two of low quality. A total of 272 primary studies were included with a median value of 38.8 (range, 6-106) which deeply analyzed for data extraction. Cross-sectional, case-control, and qualitative case studies were the most used study designs. Diarrheal diseases were the most reported outcomes representing 46% of the impact evaluations. Cholera outbreaks account for 43% of a crisis context. The research gaps were insufficient reporting of some interventions with related outcomes and the geographical distribution of current evidence. Conclusion: There is a limitation in current evidence represented by a lack of high-quality and experimental studies investigate the impact of water, sanitation and hygiene (WaSH) interventions on health and behavioral outcomes in humanitarian sittings.

Effect of Ambient Temperature on Hospital Admissions for Respiratory Disease in Suburban Rural Villages of a Semi-Arid Region in Northwest China.

OBJECTIVE: This study evaluated the effects of extreme temperatures on hospital admissions for respiratory diseases (RDs) in a semi-arid region in the Northwest of China. METHODS: Distributed lag nonlinear model was constructed, and stratified analysis by gender and age was performed. RESULTS: The exposure-response curve between temperature and RD hospital admissions was almost W-shaped. Either extremely cold temperatures or moderately cold temperatures presented a short-term acute harmful effect, and the relative risks were higher among males (1.976, 95% confidence interval [CI]: 1.773-2.203; 1.242, 95% CI: 1.203-1.282) and the elderly (2.363, 95% CI: 1.724-3.240; 1.267, 95% CI: 1.154-1.390). Both extreme and moderately hot temperatures had higher risks among females (2.040, 95% CI: 1.815-2.292; 1.328, 95% CI: 1.276-1.381). CONCLUSIONS: The relationship between air temperature and RD hospital admissions was nonlinear. Vulnerable populations varied according to extreme temperature conditions.

A scientometric analysis of indoor air pollution research during 1990-2019.

Indoor air pollution (IAP) is one of the leading risk factors for various adverse health outcomes including premature deaths globally. Even though research related to IAP has been carried out, bibliometric studies with particular emphasis on this topic have been lacking. Here, we investigated IAP research from 1990 to 2019 retrieved from the Web of Science database through a comprehensive and systematic scientometric analysis using the CiteSpace 5.7.R2, a powerful tool for visualizing structural, temporal patterns and trends of a scientific field. There was an exponential increase in publications, however, with a stark difference between developed and developing countries. The journals publishing IAP related research had multiple disciplines; 'Indoor Air' journal that focuses solely on IAP issues ranked fifth among top-cited journals. The terms like 'global burden', 'comparative risk assessment,' 'household air pollution (HAP)', 'ventilation', 'respiratory health', 'emission factor', 'impact,' 'energy', 'household', 'India' were the current topical subject where author Kirk R. Smith was identified with a significant contribution. Research related to rural, fossil-fuel toxicity, IAP, and exposure-assessment had the highest citation burst signifying the particular attention of scientific communities to these subjects. Overall, this study examined the evolution of IAP research, identified the gaps and provided future research directions.

Investigation of nickel sulfate-induced cytotoxicity and underlying toxicological mechanisms in human umbilical vein endothelial cells through oxidative stress, inflammation, apoptosis, and MAPK signaling pathways.

Growing evidence indicates that nickle and its compounds have adverse effects on the cardiovascular system. In this study, the cytotoxic insults caused by nickel sulfate (NiSO4 ) in human umbilical vein endothelial cells (HUVECs) were explored by examining cell viability, oxidative stress, inflammation, apoptosis, and MAPK signaling pathway activity. Cultured HUVECs were treated with varying concentrations of NiSO4 (0, 62.5, 250, and 1000 µM) for 24 h. Subsequently, markers of oxidative stress, inflammation, apoptosis, and MAPK signaling pathways were analyzed using biochemical assays, real-time quantitative polymerase chain reaction, and western blot. Rates of apoptosis were evaluated using flow cytometry. The results showed that NiSO4 exerted dose- and time-dependent inhibitory effects on cell growth. It induced oxidative stress and lipid peroxidation by increasing the generation of reactive oxygen species, the oxidized glutathione to reduced glutathione ratio (GSSG/GSH ratio), and malondialdehyde levels. Further, it inhibited superoxide dismutase activity in HUVECs. Flow cytometry analysis results revealed that NiSO4 (62.5-1000 µM) could induce apoptosis in HUVECs. The protein and gene expressions of cleaved Caspase 3 and Bax were elevated, and those of Bcl-2 and Bcl-XL were reduced after NiSO4 treatment. Additionally, NiSO4 triggered inflammation in HUVECs, increasing the protein and mRNA levels of IL-6 and TNF-α and reducing those of TGF-ß. Furthermore, western blot findings revealed that NiSO4 could activate MAPK signaling pathways, upregulating p38, JNK, and ERK1/2 in HUVECs by increasing the levels of p-P38，p-JNK, and p-ERK1/2 in a dose-dependent manner. MAPK pathway inhibitors (10 µM SB203580 and 10 µM SP600125) could attenuate the NiSO4 -induced increase in apoptosis and inflammation in HUVECs. They could also attenuate the dysregulation of inflammatory factors and related proteins caused by high-dose NiSO4 exposure. Interestingly, while the MEK inhibitor U0126 (10 µM) enhanced NiSO4 -induced apoptosis in HUVECs, it reduced cell inflammation. Taken together, these experimental results suggest that NiSO4 can inhibit cell growth, induce oxidative stress, and trigger subsequent inflammatory responses and apoptosis in HUVECs. These effects may be mediated by the P38 and JNK MAPK stress response pathways.

Association Between Air Pollutants and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Time Stratified Case-Crossover Design With a Distributed Lag Nonlinear Model.

Acute exacerbation of chronic obstruction pulmonary disease (AECOPD) as a respiratory disease, is considered to be related to air pollution by more and more studies. However, the evidence on how air pollution affect the incidence of AECOPD and whether there are population differences is still insufficient. Therefore, we select PM10, PM2.5, SO2, NO2, CO, and O3 as representatives combined with daily AECOPD admission data from 1 January 2015 to 26 June 2016 in the rural areas of Qingyang, northwestern China to explore the associations of air pollution with AECOPD. Based on a time-stratified case-crossover design, we constructed a distributed lag nonlinear model to qualify the single and cumulative lagged effects of air pollution on AECOPD. Stratified related risks by sex and age were also reported. The cumulative exposure-response curves were approximately linear for PM2.5, "V"-shaped for PM10, "U"-shaped for NO2 and inverted-"V" for SO2, CO and O3. Exposure to high-PM2.5 (42 µg/m3), high-PM10 (91 µg/m3), high-SO2 (58 µg/m3), low-NO2 (12 µg/m3), and high-CO (1.55 mg/m3) increased the risk of AECOPD. Females aged 15-64 were more susceptible under extreme concentrations of PM2.5, SO2, CO, and low-PM10 than other subgroups. In addition, adults aged 15-64 were more sensitive to extreme concentrations of NO2 compared with the elderly ≥65 years old, while the latter were more sensitive to high-PM10. High-SO2, high-NO2, and extreme concentrations of PM2.5 had the greatest effects on the day of exposure, while low-SO2 and low-CO had lagged effects on AECOPD. Precautionary measures should be taken with a focus on vulnerable subgroups, to control hospitalization for AECOPD associated with air pollutants.

A cross-sectional study on factors associated with hypertension and genetic polymorphisms of renin-angiotensin-aldosterone system in Chinese hui pilgrims to hajj.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular disease (CVD), however, the studies on lifestyle and genetic risks in Chinese pilgrims to Hajj was limited. The aim of this study is to examine the prevalence and associated lifestyle and genetic risks for hypertension among Hui Hajj pilgrims in China. METHODS: We performed a cross-sectional analysis of data in 1,465 participants aged 30-70 years who participated in a medical examination for Hui Hajj pilgrims from Gansu province, China in 2017. Multiple logistic regression was used to evaluate the association of potential risk factors with hypertension. Deoxyribonucleic acid (DNA) polymorphism was examined at sites in the renin-angiotensin-aldosterone system (RAAS). RESULTS: The prevalence of hypertension was 47% among this population. Lifestyle factors such as fried food preference (like vs. dislike: odds ratio [OR]: =1.53, 95% confidence interval [CI]: 1.13-2.09) and barbecued food preference (like vs. dislike: OR = 1.45, 95% CI: 1.06-1.97) were associated with elevated risk of hypertension among Hui pilgrims. Comparing with Angiotensin converting enzyme (ACE) rs4425 AA genotype, TT genotype was associated with hypertension risk (OR = 2.16, 95% CI: 1.17-4.00). Similar results were also observed for ACE rs4437 CC genotype (OR = 1.95, 95% CI: 1.07-3.55), Angiotensin II receptor (ATR) rs129876 AA genotype (OR = 4.10, 95% CI: 2.30-7.32) and Aldosterone synthase (CYP11B2) rs1912 TT genotype (OR = 2.82, 95% CI: 1.57-5.06) genotypes. CONCLUSIONS: Unhealthy lifestyle and genetic factors were associated with the prevalence of hypertension in Chinese Hui pilgrims and their interactions were also observed.

DosR antigen Rv1737c induces activation of macrophages dependent on the TLR2 pathway.

Latent Mycobacterium tuberculosis (Mtb) infection (LTBI) is the main clinical manifestation after Mtb exposure. During the latent phase, Mtb retards the attempts of eradication by the host immune system. The dormancy survival regulator (DosR) is held as essential for Mtb persistence. Rv1737c is predominantly expressed by the Mtb in latent infection. However, the role of Rv1737c in the immune evasion is still largely unknown. In this study, we have characterized the Rv1737c functions in the recruitment and activation of macrophages, which play a cardinal role in the innate and adaptive immunity. For the first time, we have revealed that Rv1737c induced the tolerogenic phenotype of macrophages by upregulating the expression of indoleamine 2,3-dioxygenase 1 (IDO1). Rv1737c-activated macrophages upregulated interleukin (IL)-4, IL-10, and Foxp3 T cells proliferation in vitro. Furthermore, the interaction of Rv1737c with macrophages was found to depend on the Toll-like receptor 2 (TLR2) pathway. It augmented nuclear factor κB (NF-κB) phosphorylation and co-stimulatory molecule expression. Thus, this study provides a crucial insight into a strategy adopted by Mtb to survive in the host by inducing tolerogenic macrophage expansion.

The DosR antigen Rv1737c from Mycobacterium tuberculosis confers inflammation regulation in tuberculosis infection.

There is an urgent need to identify the potential risk factors for activating latent Mycobacterium tuberculosis infection. In this study, we evaluated the immune function of Rv1737c, which is a latency-associated antigen of dormancy survival regulator (DosR) of M. tuberculosis in a mouse model. Our data showed that mice pretreated with recombinant Rv1737c (rRv1737c) exhibited higher levels of antigen-specific antibodies (IgG, IgM and IgA) than sham-treated mice. Following Bacilli Calmette-Guerin (BCG) challenge, rRv1737c adjuvanted with cholera toxin subunit B (CTB) induced diffuse lung inflammation and fibrosis compared to the control mice. The inflammatory pathogenesis due to rRv1737c pre-exposure was associated with a switch in the macrophage phenotype from M1 to activated M2 and was characterized by IL-10 production. Intracellular cytokine analysis further showed that the rRv1737c-pretreated mice exhibited an increased frequency of Th2 cells in the lungs, lymph nodes and spleen after BCG challenge. Furthermore, IFN-γ expression increased in the lungs after rRv1737c pretreatment compared to that in the sham mice. Accordingly, lung cells from rRv1737c-immunized mice stimulated with killed BCG produced higher levels of multiple cytokines, such as IFN-γ, IL-10 and IL-6. The results confirmed that the pathological features of rRv1737c promoted inflammation. Overall, our findings provide direct evidence of the pro-inflammatory function of rRv1737c in a murine model of BCG infection, indicating that Rv1737c is a pathogenic antigen of M. tuberculosis and may be key to the recurrence of latent infection.

Tet1-mediated DNA demethylation involves in neuron damage induced by bilirubin in vitro.

The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 µmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level. Our results showed that UCB can cause time-dependent and dose-dependent reduction of cell viability of neuronal cells, induce oxidative stress through increasing the production of ROS and increase caspase-3 activity. Quantitative real-time PCR and western blot analysis showed that UCB can inhibit Tet1 and Klotho expression in cultured neuronal cells at both the mRNA and protein level, respectively. These results are first to suggest UCB may, in part, exert its neurotoxicity through alteration of the neuronal antioxidant status and inhibition of Klotho and Tet1 gene expression. The elevation of DNA methylation in global genome through inhibition of Tet1 gene expression may, in part, play an important role in the neurotoxicity caused by UCB in vitro.

Improving Knowledge about Children's Environmental Health in Northwest China.

The main purpose of this study was to identify policy maker opinions and attitudes towards children's environmental health (CEH), potential barriers to child-specific protective legislation and implementation in northwest China, and evaluate knowledge and attitudes about CEH before and after an educational conference. We conducted seventy-two interviews with regional officials, researchers and non-governmental organization representatives from five provinces, and surveyed participants (forty-seven) before and after an educational conference in northwest China about CEH. Interviews identified general consensus among participants of the adverse effects of air pollution on children, yet few participants knew of policies to protect them. Barriers identified included limited funding and enforcement, weak regional governments and absence of child-specific policy-making. After the conference, substantially greater self-efficacy was identified for lead, mercury, air pollution and polychlorinated biphenyls (+0.57-0.72 on a 1-5 Likert scale, p = 0.002-0.013), and the scientific knowledge for the role of environment in children's health (+0.58, p = 0.015), and health care provider control (+0.52, p = 0.025) were rated more strongly. We conclude that policy makers in Northwest China appreciate that children are uniquely vulnerable, though additional regulations are needed to account for that vulnerability. Further research should examine effectiveness of the intervention on a larger scale and scope, and evaluate the usefulness of such interventions in translating research into improved care/reduced exposure to environmental hazards.

The Environment and Children's Health Care in Northwest China.

BACKGROUND: Industrialization in the northwest provinces of the People's Republic of China is accelerating rapid increases in early life environmental exposures, yet no publications have assessed health care provider capacity to manage common hazards. METHODS: To assess provider attitudes and beliefs regarding the environment in children's health, determine self-efficacy in managing concerns, and identify common approaches to managing patients with significant exposures or environmentally-mediated conditions, a two-page survey was administered to pediatricians, child care specialists, and nurses in five provinces (Gansu, Shaanxi, Xinjiang, Qinghai, and Ningxia). Descriptive and multivariable analyses assessed predictors of strong self-efficacy, beliefs or attitudes. RESULTS: 960 surveys were completed with <5% refusal; 695 (72.3%) were valid for statistical analyses. The role of environment in health was rated highly (mean 4.35 on a 1-5 scale). Self-efficacy reported with managing lead, pesticide, air pollution, mercury, mold and polychlorinated biphenyl exposures were generally modest (2.22-2.52 mean). 95.4% reported patients affected with 11.9% reporting seeing >20 affected patients. Only 12.0% reported specific training in environmental history taking, and 12.0% reported owning a text on children's environmental health. Geographic disparities were most prominent in multivariable analyses, with stronger beliefs in environmental causation yet lower self-efficacy in managing exposures in the northwestern-most province. CONCLUSIONS: Health care providers in Northwest China have strong beliefs regarding the role of environment in children's health, and frequently identify affected children. Few are trained in environmental history taking or rate self-efficacy highly in managing common hazards. Enhancing provider capacity has promise for improving children's health in the region.

[Studies of genetic polymorphism of CYP450 2E1 among the Tibetan populations in Qinghai Province and its effect on drinking behavior].

OBJECTIVE: In order to explore the effect of genetic polymorphism of CYP450 2El among the Tibetan population in Qinghai and its relationship to drinking behavior. METHODS: By the self-reported questionnaires of 325 Tibetan male who contain 193 drinkers and 132 non-drinkers, we analyzed the relationship between drinking behavior and the genetic polymorphism of CYP450 2El by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. So does the 266 Han nationalism. RESULTS: Single variable analysis showed the drinking prevalence was related to occupation, educational status, economic income, marital status and smoking (P<0.05). There were no statistical significant differences of genotypes and alleles between male Tibetan and Han population (P>0.05). The three genotypes (cl/cl, cl/c2, c2/c2) and the two alleles (cl, c2) of CYP450 2El had statistical significant differences (P<0.05) between drinkers and non-drinkers in Tibetan population, and the drinkers had higher frequencies of cl/c2 genotype and c2 allele than that of the opposite group. Compared with safe drinkers, the frequency of c2 allele in the group of dangerous was higher. The related degree of drinking behavior and amount with c2 allele were 0.17 and 0.20. The multivariate statistical analysis showed that CYP450 2E1, incomes and smoking were independent. CONCLUSION: CYP450 2E1 is the mostly influence factor to drinking behavior in male Tibetan population.

Neuroprotection of taurine against bilirubin-induced elevation of apoptosis and intracellular free calcium ion in vivo.

Previous work has shown that taurine protected neurons against unconjugated bilirubin (UCB)-induced neurotoxicity by preventing cell apoptosis and maintaining intracellular Ca²âº homeostasis in primary neuron culture. This study investigates the neurotoxicity of hyperbilirubinemia and neuroprotection of taurine in a clinically relevant murine model in vivo. A hyperbilirubinemia baby mice model was established by intraperitoneal injection with UCB. After 24 h, the neural apoptotic level, transcriptional activity of caspase-3, and iCa²âº concentration were detected. It was found that UCB injection significantly increased both intracellular free Ca²âº concentrations and the activities of proapoptosis protease caspase-3, which is related to the elevation of neural apoptosis level. When baby mice were pretreated with 7.5 or 15 mg/kg body weight (bw) taurine for 4 h and then exposed to UCB, apoptotic death was significantly attenuated through down-regulation of activity of caspase-3 and i[Ca²âº] in the brain. From these observations, it was concluded that taurine limits bilirubin-induced neural damage by inhibiting iCa²âº overload as well as decreasing activation of proapoptotic proteases caspase-3. This study might contribute to the development of taurine as a broad-spectrum agent for preventing and/or treating neural damage in neonatal jaundice.

[Genetic polymorphism of ADH3 and ALDH2 among Tibetan population in Qinghai and its relationship with drinking behavior].

OBJECTIVE: To investigate the genetic polymorphism of ADH3 and ALDH2 among Tibetan population in Qinghai and its relationship with drinking behavior. METHODS: Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) technique was used to detect the genotype of ADH3 and ALDH2. Drinking behavior was obtained by questionnaire. RESULTS: The frequency of ADH3*2 and ALDH2*2 alleles in Tibetan population was 7.79% and 22.21% respectively, the frequency of ALDH2*2 and ADH3*1 alleles in non-drinkers was higher than that in drinkers, and the frequency of ALDH2*2 and ADH3*1 alleles in risk drinkers was lower than that in safe drinkers. CONCLUSION: ADH3 and ALDH2 are associated with drinking behavior in male Tibetan population.

Taurine protects against bilirubin-induced neurotoxicity in vitro.

Kernicterus is a bilirubin-induced encephalopathy in newborn. Its spectrum ranges from subtle extrapyramidal to acute encephalopathy and chronic posticteric sequelae. Current treatment of this serious problem is far from optimal. Taurine has been documented to have protective effects on neuronal cells against ischemia in vivo and in vitro. This study used primary neuronal culture to investigate the toxicological effects of unconjugated bilirubin (UCB) and the protection of taurine against UCB-mediated neuron damage. Dose-dependent reduction of cell viability was found. Changes in neurite outgrowth preceded the reduction of cell viability. The bilirubin-mediated neurotoxicity is mainly due to increased rate of cell apoptosis and higher levels of intracellular free calcium ion level. Taurine dramatically improved cell viability in cultured neurons exposed to 12.5microM UCB. Taurine pretreatment reduced UCB-mediated apoptotic cell death in primary cultured neurons in a concentration-dependent manner, which was associated with reversal of the increased intracellular free calcium ion levels caused by UCB. This study suggests the potential of taurine as a broad-spectrum agent for preventing and/or treating neuronal damage in neonatal jaundice.