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Abstract Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.

IgE antibodies elicit powerful immune responses, recruiting effector cells to tumors more efficiently and with greater cytotoxicity than IgG antibodies. Consequently, IgE antibodies are a promising alternative to conventional IgG-based therapies in oncology (AllergoOncology). As the pharmacokinetics of IgE antibodies are less well understood, we used molecular imaging in mice to compare the distribution and elimination of IgE and IgG antibodies targeting the human tumor-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4). Anti-CSPG4 IgE and IgG1 antibodies with human Fc domains were radiolabeled with 111In. CSPG4-expressing A375 human melanoma xenografts implanted in NOD-scid IL2rg-/- mice were also engrafted with human immune cells by intravenous administration. 111In-anti-CSPG4 antibodies were administered intravenously. Their distribution was determined by single-photon emission computed tomography (SPECT) and ex vivo gamma-counting over 120 h. SPECT imaging was conducted from 0 to 60 min after antibody administration to precisely measure the early phase of IgE distribution. 111In-labeled anti-CSPG4 IgG and IgE showed serum stability in vitro of >92% after 5 days. In A375 xenograft-bearing mice, anti-CSPG4 IgE showed much faster blood clearance and higher accumulation in the liver compared to anti-CSPG4 IgG. However, tumor-to-blood and tumor-to-muscle ratios were similar between the antibody isotypes and higher compared with a non-tumor-targeting isotype control IgE. IgE excretion was much faster than IgG. In non-tumor-bearing animals, early SPECT imaging revealed a blood clearance half-life of 10 min for IgE. Using image-based quantification, we demonstrated that the blood clearance of IgE is much faster than that of IgG while the two isotypes showed comparable tumor-to-blood ratios.

Abstract Background The effects of temperature and relative humidity on different types of children’s allergic diseases have not been comprehensively evaluated so far. This study aims to assess the impact of temperature and relative humidity variability on children’s allergic diseases and to identify the critical time window. Methods We collected outpatient data on allergen testing in children between July 2020 and January 2022 from the Affiliated Children’s Hospital of Nanjing Medical University. We defined the 1st, 10th, 90th, and 99th percentiles as extreme cold, moderate cold, moderate hot, and extreme hot for temperature, and as low, moderate high, and extreme high for relative humidity, respectively. A distributed lag nonlinear model (DLNM) combined with a binomial regression model was used to assess the possible nonlinear relationship at different periods. Subgroup analysis by gender and age was conducted. Results We found that extreme and moderate cold temperatures were positively associated with skin allergies and total allergies (28 days: OR = 4.69, 95% CI: 2.88, 7.63; OR = 3.36, 95% CI: 2.39, 4.73) and (28 days: OR = 3.76, CI: 2.43, 5.81; OR = 2.71, 95% CI: 2.00, 3.68), respectively. Moderate and extreme hot temperatures were negatively associated with food allergies (28 days: OR = 0.13, 95% CI: 0.04, 0.41 and OR = 0.04; 95% CI: 0.01, 0.27). Low relative humidity was negatively associated with respiratory allergies, skin allergies, and total allergic diseases (28 days: OR = 0.26, 95% CI: 0.10, 0.71; OR = 0.29, 95% CI: 0.15, 0.55; and OR = 0.42, 95% CI: 0.26, 0.68). Meanwhile, extreme high relative humidity was negatively associated with respiratory allergies, and positively associated with skin allergies, food allergies, and total allergies (28 days: OR = 0.16, 95%CI: 0.07, 0.37; OR = 3.60, 95% CI: 2.52, 5.14; OR = 15.61, 95% CI: 3.23, 75.56; and OR = 2.33, 95% CI: 1.73, 3.15). A stronger relationship between temperature, relative humidity, and allergic diseases was observed in children under 5 years, specifically girls. Conclusions Our study provides evidence that temperature and relative humidity variability may be associated with allergic diseases, however, the directionality of the relationship differs by allergic type.

BackgroundThyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy.MethodsOur study employed a combination of meta-analysis and case-control design. For the meta-analysis, we conducted a systematic search of online databases for studies that compared thyroid function tests in children with neurological disorders to controls. In our case-control study, we recruited a total of 11836 children, comprising 7035 cases and 4801 healthy controls. Wilcoxon Rank Sum Test was used to determine characteristics of thyroid function between the cases and healthy controls. In order to exclude the false discovery rate (FDR), the Benjamini-Hochberg (BH) procedure is applied.ResultsA total of 12 relevant literature sources were included in the meta-analysis. Compared with controls, free thyroxine (FT4) levels were significantly decreased in neurological disorders in meta-analysis (MD = -0.29, 95% CI: -0.50 to -0.09), whereas thyroid-stimulating hormone (TSH) levels showed no significant difference (MD = -0.07, 95% CI: -0.36 to 0.21). In our case-control study, levels of free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and anti-thyroglobulin antibodies (TG-Ab) were notably reduced among individuals with neurological disorders, compared with healthy controls (P

Abstract Introduction Over the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls. Methods We enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset. Results A total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p

BackgroundWhile vitamin deficiencies can pose serious health consequences for the body, excessive intake of vitamins can also lead to health risks. However, there is limited data about the impact of multivitamins on neurological and growth disorders. This study aimed to investigate the relationship between multivitamins and neurological and growth disorders.MethodsA cross-sectional study was conducted with 16,921 subjects who visited the Children’s Hospital of Nanjing Medical University from 2019 to 2021. The subjects were categorized into two groups based on their health status including 9,368 cases (4,484 with neurological disorders and 4,884 with growth disorders) and 7,553 healthy controls. Statistical tests including the T-test, Wilcoxon Rank Sum test, and Chi-Square test were employed to compare the groups, and logistic regression and Weighted Quantile Sum (WQS) regression were used to identify associations.ResultsIn the adjusted logistic regression, serum 25 hydroxyvitamin D [25(OH)D], vitamin B2, and vitamin B9 were associated with decreasing risks of neurological disorders, whereas vitamin A, vitamin B1, and vitamin B12 were associated with increasing risks of neurological disorders. Nevertheless, vitamin A and vitamin B2 were associated with increasing risks of growth disorders. In the WQS model, nine multivitamins were positively associated with risks of neurological disorders, and Vitamins D and C were weighted the most. In addition, the inverse association but not statistically significant was observed between multivitamins and growth disorders, particularly growth retardation revealed a negative association, and some individual growth disorders revealed positive associations including obesity and malnutrition.ConclusionIn general, the study observed that multivitamins may be associated with neurological and growth disorders either positive or negative depending on the type of disorder.

BackgroundEvidence from animal experiments and epidemiological studies has reported controversial results about the effects of prenatal bisphenols (BPs) exposure on childhood thyroid function. This study aims to explore the associations of prenatal exposure to BPs with thyroid-related hormones (THs) in newborns and early childhood, with a particular focus on the sex-dependent and exposure level effects.MethodsCorrelated studies were systematically searched from PubMed, Web of Science, Medline, Cochrane, and Embase until February 21, 2024. The exposures assessed include bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and tetrachlorobisphenol A (TCBPA). THs measured were thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), free tri-iothyronine (FT3), and free thyroxine (FT4). Effect estimates were quantified using coefficients from multivariable regression models. Statistical analyses were completed using Stata 16.0. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS).ResultsEleven cohort studies comprising 5,363 children were included in our meta-analysis. Prenatal bisphenol concentrations were statistically significant related to alterations in thyroid hormones in children, exclusively in female offspring, including reduced TSH (β = -0.020, 95% CI: -0.036, -0.005) and increased TT3 levels (β = 0.011, 95% CI: 0.001, 0.021), and exposure to high concentration of bisphenols (>1.5 ug/g creatinine) significantly reduced FT3 levels in children (β = -0.011, 95% CI: -0.020, -0.003).ConclusionPrenatal bisphenol exposure is linked to alterations in thyroid hormone levels in girls, necessitating enhanced measures to control bisphenol exposure levels during pregnancy for child health protection.Systematic Review Registrationhttps://inplasy.com, identifier INPLASY202450129.

Abstract Background Clonidine stimulation test has been widely used in the diagnosis of growth hormone deficiency in children with short stature with a high level of reliability. However, it may cause hypotension, which usually appears as headache, dizziness, bradycardia, and even syncope. It is well known that elevating the beds to make patients’ feet above their cardiac level might relieve this discomfort. However, the real efficiency of this method remains to be proved while the best angle for the elevated bed is still unclear. Methods A total of 1200 children with short stature were enrolled in this retrospective cross-sectional study. Age, gender, weight, and basic systolic and diastolic blood pressure were collected. Blood pressure at 1, 2, 3, and 4 h after stimulation tests were recorded. The participants were divided into 3 groups based on the angles of the elevated foot of their beds named 0°, 20°, and 40° groups. Results At one hour after the commencement of the tests, participants lying on the elevated beds showed a higher mean increase on the change of pulse pressure. The difference in the angles of the elevated beds did not show statistical significance compared with those who did not elevate their beds (0.13 vs. 2.83, P = 0.001; 0.13 vs. 2.18, P = 0.005; 2.83 vs. 2.18, P = 0.369). When it came to 4 h after the tests began, participants whose beds were elevated at an angle around 20° had a significantly higher mean increase in the change of pulse pressure values compared with those whose beds were elevated at an angle around 40° (1.46 vs. -0.05, P = 0.042). Conclusion Elevating the foot of the beds of the patients who are undergoing clonidine stimulation tests at an angle of 20°might be a good choice to alleviate the hypotension caused by the tests.

There is limited evidence about the gender- and obesity-specific effects of personal care product and plasticizing chemicals (PCPPCs) on short sleep duration in adults. We evaluated the gender- and obesity-specific association of co-exposure to PCPPCs and short sleep duration among adults aged 20–60 years using the National Health and Nutrition Examination Survey (NHANES) 2011–2016, a secondary data source from the United States. Seventeen PCPPCs, including five phenols, two parabens, and ten phthalates, were detected, and sleep duration was assessed among 3012 adults. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed. We found that bisphenol A (BPA), mono (caboxy-isooctyl) phthalate (MCOP), and mono (3-carboxypropyl) phthalate (MCPP) were consistently positively associated with short sleep duration in both females and males regardless of obesity status, except for BPA with general obesity. In particular, mono benzyl phthalate (MBzP) revealed a positive association in females, mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) revealed a positive association in males, and MiBP revealed a positive association in abdominal obesity. Similar associations were observed in the mixture. Our study highlights that PCPPCs are independently associated with an increasing risk of short sleep duration in adults both individually and as a mixture; however, gender- and obesity-specific differences may have little effect on certain individual PCPPCs on short sleep duration.

ABSTRACT: The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007‐2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (β = ‐0.209 (95% CI: ‐0.310, ‐0.114)), and caused an increased Tg concentration (β = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and β =‐0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and β =‐0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.

Abstract Background Recently the prevalence of precocious puberty development is increasing among Chinese children. Proper understanding of the risk factors for precocious puberty in children is pivotal as could help to improve children's health. This study aims to evaluate the effect of environmental factors on precocious puberty in children. Methods We matched the cases and controls by age at the ratio of 1:1 (201 cases and 201 controls) for girls and 1:4 (24 cases and 96 controls) for boys. We used conditional logistic regression to explore the effect of environmental factors on precocious puberty, and a random forest model to identify the most important risk factor. Results In the multivariate regression, cesarean section (OR = 1.99, 95% CI: 1.05, 3.76), child body mass index [BMI] (OR = 1.25, 95% CI: 1.10, 1.43), maternal BMI (OR = 1.13, 95%CI: 1.01, 1.26), and exposure to secondhand smoke several times a month but less than once a week (OR = 4.09, 95%CI: 1.79,9.35), and almost every day (OR = 6.48, 95% CI: 2.14, 19.56) were risk factors for precocious puberty in girls. While maternal height (OR = 0.82, 95% CI: 0.75, 0.88), paternal height (OR = 0.91, 95% CI: 0.85, 0.98), bedtime at night (OR = 0.30, 95% CI: 0.17, 0.51), and night sleep (OR = 0.43, 95% CI: 0.21, 0.86) were protective factors. In boys, only exposure to secondhand smoke several times a month but less than once a week (OR = 7.94, 95% CI: 1.25, 50.33) was a risk factor for precocious puberty. In the random forest model, Child BMI was the most important risk factor for precocious puberty in girls. Conclusions Our findings suggest that environmental factors were associated with precocious puberty in children, particularly in girls.

Background: Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors. Methods: A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyze d. Results: All 204 cases were treated with methimazole at presentation wi th GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR) = 2.510, 95% CI: 1.561–4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR = 0.452, 95% CI: 0.232–0.879). Conclusion: GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affe ct the prognosis.

Abstract Background Ozone as an air pollutant is gradually becoming a threat to people's health. However, the effect of ozone exposure on risk of developing diabetes, a fast-growing global metabolic disease, remains controversial. Objective To evaluate the impact of ambient ozone exposure on the incidence rate of type 1, type 2 and gestational diabetes mellitus. Method We systematically searched PubMed, Web of Science, and Cochrane Library databases before July 9, 2022, to determine relevant literature. Data were extracted after quality evaluation according to the Newcastle Ottawa Scale (NOS) and the agency for healthcare research and quality (AHRQ) standards, and a meta-analysis was used to evaluate the correlation between ozone exposure and type 1 diabetes mellitus (T1D), type 2 diabetes mellitus (T2D), and gestational diabetes mellitus (GDM). The heterogeneity test, sensitivity analysis, and publication bias were performed using Stata 16.0. Results Our search identified 667 studies from three databases, 19 of which were included in our analysis after removing duplicate and ineligible studies. Among the remaining studies, three were on T1D, five were on T2D, and eleven were on GDM. The result showed that ozone exposure was positively correlated with T2D [effect size (ES) = 1.06, 95% CI: 1.02, 1.11] and GDM [pooled odds ratio (OR) = 1.01, 95% CI: 1.00, 1.03]. Subgroup analysis demonstrated that ozone exposure in the first trimester of pregnancy might raise the risk of GDM. However, no significant association was observed between ozone exposure and T1D. Conclusion Long-term exposure to ozone may increase the risk of T2D, and daily ozone exposure during pregnancy was a hazard factor for developing GDM. Decreasing ambient ozone pollution may reduce the burden of both diseases.

Gabon is one of 11 high-forest, low-deforestation (HFLD) countries in the world. It has the highest proportion of preserved forests in the Congo Basin and is the first country to create large forest carbon offset credits in the market. However, about 60% of forests in Gabon is allocated to logging concessions, causing concerns for forest degradation and the sustainability of carbon credits. Here, we use a combination of air- and space-borne remote sensing data and the-state-of-the-art gradient boosted regression trees to estimate forest structure and aboveground biomass carbon density (ACD) of trees at 100 m resolution for the year circa 2020. Mapping spatial variations of ACD across floristically diverse landscapes, we estimate average density and total living carbon storage of trees at the national and sub-national levels. The estimated ACD of trees in forestlands within the country was 142.12 ± 7.3 Mg C ha ^−1 with the highest values found in central Gabon (150.08 ± 5.8 Mg C ha ^−1 ) and on highlands (161.18 ± 6.7 Mg C ha ^−1 ). On average, in every region, ACD of forests found within logging concessions (149.89 ± 6.1 Mg C ha ^−1 ) was higher than unmanaged forests of unprotected areas (122.81 ± 4.4 Mg C ha ^−1 ), indicating the combined effects of logging in carbon-rich forests and increased productivity due to management. The country’s total estimated biomass carbon for trees (above and belowground) stored within the forests was 4.14 ± 0.3 Pg C with 68% found within logging concessions and 14% within protected areas. The map provides high precision and comprehensive assessment of carbon stocks of trees in Gabon’s forests, significantly improving the country’s prospects to implement climate mitigation policies and to participate in carbon markets.

Abstract Background Gynecological diseases have been taken attention and studied worldwide. Although, no recent studies have delineated the magnitude of gynecological diseases among Chinese women. This study aims to evaluate the current situation of menstruation and gynecological diseases prevalence among Chinese women. Methods A cross-sectional study was conducted at a hospital affiliated with Nanjing medical university in Nanjing, China between September 2021 and February 2022. A sample size of 977 women aged 18–52 years participated in a face-to-face interview questionnaire. Logistic regression was performed to determine whether pubertal timing and menstrual characteristics were associated with gynecological diseases. Results The most prevalent gynecological disease was dysmenorrhea (45.96%), followed by polycystic ovary syndrome, PCOS (19.04%), uterine fibroids (14.23%), spontaneous abortion (13.20%), trouble conceiving (12.59%), ovarian dysfunction (11.16%) and endometriosis (4.09%). In the adjusted model, heavy bleeding with large clots was associated with an increased risk of dysmenorrhea (odds ratio, OR = 5.01, 95% Confidence interval, CI 2.26, 11.10; p = 0.000), while history of precocious puberty diagnosis was associated with a reduced risk of dysmenorrhea (OR = 0.50, 95%CI: 0.26, 0.94; p = 0.031). Regular menstrual cycle in the past 12 months and regular menstrual periods were associated with decreased risk of PCOS (OR = 0.44, 95%CI 0.30, 0.65; p = 0.000) and (OR = 0.52, 95%CI 0.36, 0.74; p = 0.000), respectively. Histories of early thelarche, early menarche, and precocious puberty diagnosis were associated with increased risk of ovarian dysfunction (OR = 1.96, 95%CI 1.25, 3.08, p = 0.004), (OR = 2.26, 95%CI 1.24, 4.13; p = 0.008) and (OR = 2.79, 95%CI 1.36, 5.74; p = 0.005), respectively. Heavy bleeding and heavy bleeding with large clots were associated with endometriosis (OR = 4.92, 95%CI 1.50, 16.15, p = 0.009) and (OR = 5.67, 95%CI 1.42, 22.56; p = 0.014), respectively. Conclusions The prevalence of gynecological diseases is increasing among Chinese women and pubertal timing and menstrual characteristics may be associated with some gynecological diseases, specifically dysmenorrhea, PCOS, ovarian dysfunction, and endometriosis.

Abstract Zeolite can impart antibacterial properties to dental materials in the long-term when incorporated with inorganic cations. However, due to its porosity, it may jeopardize the mechanical integrity of the dental material. The aim of this project was to determine the effect on physical properties when zeolite is added to commercially available Ag-reinforced Glass Ionomer Cement (GIC). Sample groups were prepared according to the percentage of zeolite-clinoptilolite (0% - control, 0.5%, 1%, 2%, and 4% wt) added to Ag-GIC. Water sorption, solubility, Vickers hardness, and flexural strength were determined. Specifically, 10 × 2 mm circular disks were fabricated for the Vickers hardness, water sorption, and water solubility tests and 25 × 5 × 2 mm bars were created for the flexural strength test. The results from the surface hardness, water sorption, and flexural strength tests suggested that adding 0.5–4% wt of zeolite to Ag-reinforced GIC did not diminish its physical properties. However, the water solubility results showed that higher concentrations (2–4% wt) of zeolite had a statistically significant increase in water solubility compared to the control. Up to 4% wt zeolite can be incorporated into Ag-reinforced GIC without compromising mechanical properties. Incorporation of 0.5–1% wt zeolite to Ag-reinforced GIC will maintain an adequate surface hardness, water sorption, and flexural strength without compromising water solubility. Further research is needed to determine the effects of higher water solubility on clinical efficacy of zeolite modified Ag-GIC. Graphical abstract

There is an argument that BPA substitutes may have the same or more deleterious health effects as BPA due to their structural similarity. This study explored the association between urinary BPA substitutes and precocious puberty among girls by including 120 girls with precocious puberty (cases) aged 2–10 years enrolled at Nanjing Children’s Hospital Department of Endocrinology in China between April 2021 to September 2021 and 145 healthy girls (controls) recruited from a primary school. Logistic regression was used to evaluate the effect of single exposures, and Bayesian kernel machine regression (BKMR) and quantile-based g-computation were used for the mixed effect. In the multivariate logistic regression, BPS (bisphenol S), TBBPA (tetrabromobisphenol A), and BPFL (bisphenol-FL) were significantly associated with increased risk of precocious puberty (odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.13, 2.76, p = 0.014), (OR = 1.46, CI: 1.06, 2.05; p = 0.023), and (OR = 1.47, CI: 1.01, 2.18; p = 0.047), respectively. The BMKR and quantile-based g-computation models revealed consistent associations for single exposures and there was insufficient evidence for the associations of the mixed exposure of bisphenols with precocious puberty. In conclusion, BPA substitutes such as BPS, TBBPA, and BPFL may be associated with an increased risk of precocious puberty in girls.

The study is aimed at assessing the impacts of postharvest handling practices on the quality and safety of tuna sold at the Honiara Fish Market (HFM), Solomon Islands. Two major approaches were adopted: (1) face-to-face interviews of 60 participants using questionnaires and physical observations of the supply chains and postharvest handling practices and (2) determination of time-temperature, quality index, histamine, and microbial load of tuna and contact surfaces. Sampling was conducted on both the wet season (WS) and dry season (DS), of which 36 samples from both batches of fresh tuna (FT) and brined tuna (BT) were analyzed. Three critical control points (CCPs) were identified in the supply chains of both FT and BT, where samples were obtained for scientific analyses. The average body temperature for WS tuna exposed for 9-10 h with low or no ice after catch was 3°C for FT and 15°C for BT, while DS samples were 26°C and 31°C for FT and BT, respectively. The quality index (QI) for WS showed a significant difference (P

Cassava (Manihot esculenta Crantz) is a staple crop for ~800 million people in sub-Saharan Africa. Its production and productivity are being heavily affected by the two viral diseases: cassava brown streak disease (CBSD) and cassava mosaic disease (CMD), impacting greatly on edible root yield. CBSD is currently endemic to central, eastern and southern Africa, if not contained could spread to West Africa the largest cassava producer and consumer in the continent. Genomic selection (GS) has been implemented in Ugandan cassava breeding for accelerated development of virus resistant and high yielding clones. This study leveraged available GS training data in Uganda for pre-emptive CBSD breeding in W. Africa alongside CMD and fresh root yield (FRW). First, we tracked genetic gain through the current three cycles of GS in Uganda. The mean genomic estimated breeding values (GEBVs), indicated general progress from initial cycle zero (C0) to cycle one (C1) and cycle two (C2) for CBSD traits and yield except for CMD. Secondly, we used foliar data of both CBSD and CMD, as well as harvest root necrosis and yield data to perform cross-validation predictions. Cross-validation prediction accuracies of five GS models were tested for each of the three GS cycles and West African (WA) germplasm as a test set. In all cases, cross-validation prediction accuracies were low to moderate, ranging from -0.16 to 0.68 for CBSD traits, -0.27 to 0.57 for CMD and -0.22 to 0.41 for fresh root weight (FRW). Overall, the highest prediction accuracies were recorded in C0 for all traits tested across models and the best performing model in cross-validation was G-BLUP. Lastly, we tested the predictive ability of the Ugandan training sets to predict CBSD in W. African clones. In general, the Ugandan training sets had low prediction accuracies for all traits across models in West African germplasm, varying from -0.18 to 0.1. Based on the findings of this study, the cassava breeding program in Uganda has made progress through application of GS for most target traits, but the utility of the training population for pre-emptive breeding in WA is limiting. In this case, efforts should be devoted to sharing Ugandan germplasm that possess resistance with the W. African breeding programs for hybridization to fully enable deployment of genomic selection as a pre-emptive CBSD breeding strategy in W. Africa.

Abstract Background Due to the rapid spread of coronavirus disease 2019 (COVID-19) worldwide, it is necessary to ascertain essential immune inflammatory parameters that describe the severity of the disease and provide guidance for treatment. We performed network meta-analyses to determine differences in blood cells, lymphocyte subsets, and cytokines in COVID-19 patients with different clinical stages. Methods Databases were systematically searched to May 2, 2020, and updated on June 1, 2020. Network meta-analyses were conducted via Stata 15.0, and the mean difference (MD) and its 95% CI were used as the effect values of the pooled analysis. Results Seventy-one studies were included involving 8647 COVID-19 patients, White blood cell (WBC), neutrophil (NEUT), IL-6, and IL-10 counts increased significantly with worsening of the COVID-19, while lymphocyte (LYM) counts decreased. The levels of platelet (PLT), CD3+, CD4+, CD8+, and CD19+ cells in severe and critical patients were significantly lower than those in mild patients. IL-1β count was significantly elevated in critical patients. Conclusions Immune suppression and inflammatory injury play crucial roles in the progression of COVID-19, and the identification of susceptible cells and cytokines provide guidance for the early and accurate treatment of COVID-19 patients.

Objective: Ion-incorporated zeolite is a widely used antimicrobial material studied for various dental applications. At present, there is no other systematic review that evaluates the effectiveness of zeolite in all dental materials. The purpose of this study was to review all available literature that analyzed the antimicrobial effects and/or mechanical properties of zeolite as a restorative material in dentistry. Material and methods: Following PRISMA guidelines, an exhaustive search of PubMed, Ovid Medline, Scopus, Embase, and the Dentistry & Oral Sciences Source was conducted. No language or time restrictions were used and the study was conducted from June 1, 2020 to August 17, 2020. Only full text articles were selected that pertained to the usage of zeolite in dental materials including composite resin, bonding agents, cements, restorative root material, cavity base material, prosthesis, implants, and endodontics. Results: At the beginning of the study, 1534 studies were identified, of which 687 duplicate records were excluded. After screening for the title, abstract, and full texts, 35 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for each of the 35 articles chosen. Conclusion: Although ion-incorporated zeolite may enhance the antimicrobial properties of dental materials, the mechanical properties of some materials, such as MTA and acrylic resin, may be compromised. Therefore, since the decrease in mechanical properties depends on zeolite concentration in the restorative material, it is generally recommended to add 0.2-2% zeolite by weight.

La cartographie de l’occupation du sol du Gabon en 2010 et 2015 et celle des changements entre ces deux dates a été réalisée dans le cadre du programme OSFACO [1] par l'Agence Gabonaise d'Etudes et d'Observations Spatiales (AGEOS). Il s’agit de la première carte d’occupation du sol de référence à l’échelle nationale dont la légende est issue d’une concertation des acteurs majeurs du secteur forestier gabonais. Cette carte a été obtenue en affinant celle du couvert forestier du Gabon (forêt/non forêt) obtenue dans le cadre des projets OSFT [2] et GEOFORAFRI [3]. La cartographie s’est basée sur l’utilisation des images satellitaires SPOT 5/7, Sentinel 2 pour l’année 2015 et les images SPOT 4, ASTER et ALOS 1 pour l’année 2010. Les méthodes de classification semi-automatisée et d'amélioration manuelle ont été combinées pour une meilleure précision des classes d’occupation du sol. Les résultats obtenus mettent en évidence 10 classes d’occupation du sol représentant les grands ensembles paysagers du pays, dominés par les forêts qui occupent 89% de la superficie totale du Gabon en 2015. Les classes d’occupation du sol qui ont le plus évolué entre 2010 et 2015 sont les forêts, les savanes, les terres agricoles et les surfaces artificialisées. Les principales pertes en forêt sont liées à la conversion des forêts vers les surfaces artificialisées, les terres cultivées et les sols nus. Les gains en forêt les plus importants quant à eux sont observés au niveau de la fermeture des pistes forestières. La validation du produit, réalisée par une équipe indépendante de celle qui a produit la carte, s’est basée sur une donnée de référence issue d’un plan d’échantillonnage combinant une composante systématique et aléatoire suivant la méthodologie de Sannier et al. (2016). L’analyse de la correspondance entre la donnée d’occupation du sol produite et la donnée de référence a permis d’estimer la précision globale à 95%. [1] Observation Spatiale des Forêts d’Afrique Centrale et de l’Ouest, projet financé par l’Agence Française de Développement (AFD), de 2016 à 2020. [2] Observation Spatiale des Forêts tropicales, projet financé par l’AFD, de 2011 à 2015. [3] Renforcement des capacités et accès aux données satellitaires pour le suivi des forêts en Afrique Centrale et de l’Ouest, projet financé par le Fonds Français pour l'Environnement Mondial (FFEM), de 2012 à 2017.

Polymethyl methacrylate (PMMA), an acrylic resin used in orthodontic appliances and removable dentures for its biocompatibility and esthetics, may harbor bacteria on its surface. The present study investigated a new PMMA formula with Gantrez: an antibacterial copolymer of methyl vinyl ether and maleic acid (PVM/MA). Samples were tested for mechanical properties (surface hardness, flexural strength, water sorption, and water solubility) and effects against Streptococcus mutans. Six groups (0%-control, 5%, 10%, 15%, 20%, and 25% Gantrez) of n = 12 were fabricated for physical property tests and analyzed with one-way ANOVA and Prism 6. From these results, three groups (0%, 5%, and 10% Gantrez) were selected for antibacterial tests, and data were analyzed with one-way ANOVA and Tukey’s multiple comparison test. Adding 5% and 10% Gantrez into PMMA significantly decreased S. mutans adhesion. There was no significant difference between the control vs. 5%, 10%, 15%, and 20% Gantrez (p > 0.05) for surface hardness, the control vs. 5% Gantrez (p > 0.05) for flexural strength, and the control vs. 5 and 10% Gantrez for water sorption and water solubility. Overall, incorporating 5% Gantrez into PMMA may be a promising solution to reduce bacterial adhesion without changing the acrylic resin’s physical properties.

Background: Triclosan (TCS) is an environmental chemical with endocrine disrupting effects and can enter the body through the skin or oral mucosa. Human data about the effect of TCS exposure during pregnancy on neonatal birth weight and TCS exposure during childhood on children's growth are scarce.Objectives: To investigate the association between maternal urinary TCS level and neonatal birth weight, as well as children's urinary TCS level and children's body mass index (BMI).Methods: A systematic literature search was conducted using PubMed, Cochrane Library, and Web of Science. Finally, seven epidemiological articles with 5,006 participants from September 25, 2014 to August 10, 2018 were included in the meta-analysis to identify the relationship between maternal exposure to TCS and neonatal birth weight. On the other hand, three epidemiological articles with 5,213 participants from July 22, 2014 to September 1, 2017 were included in another meta-analysis to identify the relationship between children's exposure to TCS and children's BMI. We used Stata 16.0 to test the heterogeneity among the studies and calculating the combined effect value 95% confidence interval (CI) of the selected corresponding models.Results: TCS exposure during pregnancy was not significant associated with neonatal birth weight. The results of forest plots were as follows: ES (Estimate) = 0.41 (95% CI: −11.97–12.78). Children's urinary TCS level was also irrelevant associated with children's BMI: ES = 0.03 (95% CI: −0.54–0.60).Conclusions: This meta-analysis demonstrated that there was no significant association between maternal TCS level and neonatal birth weight, also there has no relationship between children's urinary TCS level and children's BMI.

Achieving food security for an ever-increasing human population requires faster development of improved varieties. To this end, assessment of genetic gain for key traits is important to inform breeding processes. Despite the improvements made to increase production and productivity of cassava in Uganda at research level, there has been limited effort to quantify associated genetic gains. Accordingly, a study was conducted in Uganda to assess whether or not genetic improvement was evident in selected cassava traits using cassava varieties that were released from 1940 to 2019. Thirty-two varieties developed during this period, were evaluated simultaneously in three major cassava production zones; central (Namulonge), eastern (Serere), and northern (Loro). Best linear unbiased predictors (BLUPs) of the genotypic value for each clone were obtained across environments and regressed on order of release year to estimate annual genetic gains. We observed that genetic trends were mostly quadratic. On average, cassava mosaic disease (CMD) resistance increased by 1.9% per year, while annual genetic improvements in harvest index (0.0%) and fresh root yield (−5 kg per ha or −0.03% per ha) were non-substantial. For cassava brown streak disease (CBSD) resistance breeding which was only initiated in 2003, average annual genetic gains for CBSD foliar and CBSD root necrosis resistances were 2.3% and 1.5%, respectively. It’s evident that cassava breeding has largely focused on protecting yield against diseases. This underpins the need for simultaneous improvement of cassava for disease resistance and high yield for the crop to meet its current and futuristic demands for food and industry.

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5–21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group.Our data showed that prenatal PM exposure caused the offspring mice’s anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.

Many jurisdictions have put forward guidelines to identify sites at risks of soil degradation with the extraction of logging residues. Most guidelines are based on expert opinion and use the precautionary principle because of the lack of strong understanding of what makes a site sensitive to intensive biomass removal. Two main approaches are used: 1-identifying thresholds for specific site properties 2- developing nutrient budget indicators to rate the potential for nutrient deficit. Thanks to the development of digital soil mapping, it is becoming easier to develop maps for such indicators. A crucial question is the reliability of the different indicators. One way of evaluating their reliability is to test the coherence between the geographic locations of sites rated as sensitive by different indicators. In this study, we developed maps of key soil properties and of biogeochemical fluxes for the managed forest land of Canada at a resolution of 250 m. We used three site properties (slope, pH and sand content), as well as three nutrient budget indicators (N Budget, Base cation (BC) Budget and N Stability ratio) that were mapped and compared. The results indicated very little overlap between the areas identified as sensitive by the three site property indicators and very little concordance between sites rated as sensitive by site property indicators and those identified as sensitive by nutrient budget indicators while nutrient budget indicators showed coherence among themselves. Because nutrient budget indicators were found to be more dependent on the amount of nutrient extracted in the harvested biomass, than on the rates of nutrient inputs from the soil or the atmosphere, they tended to rate productive sites as sensitive, to the opposite of site property indicators. These results suggest that different indicators are assessing different processes and different aspects of site sensitivity. Because of the lack of coherence amongst the indicators, it is advisable 1) to use indicators based on the results of long-term monitoring plots, 2) to maintain such long-term observations and 3) to leave on the ground a substantial proportion of harvest residues, especially on sites evaluated as sensitive.

Objectives:. To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. Design:. A multicenter, prospective, observational study was performed between August 2018 and January 2019. Setting:. Community and academic hospitals in the United States. Participants:. Emergency medicine clinical pharmacists. Interventions:. Recommendations classified into one of 38 intervention categories associated with cost avoidance. Measurements and Main Results:. Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1. Conclusions:. Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.

INTRODUCTION: Studies on urinary tract infections (UTIs) in West Africa from 1990 to 2012 have showed moderate to high antimicrobial resistance to commonly prescribed antibiotics. Fluoroquinolones have been the main stay in the management of UTIs, but recent reports show emergence of resistance. Levofloxacin and ciprofloxacin still remain the commonest fluoroquinolones prescribed for UTIs in many settings. objective: this study sought to compare activity of ciprofloxacin and levofloxacin against clinical isolates obtained from patients with suspected UTI at the Ghana Police Hospital.

The real Brittany would be the one where Breton language is spoken, the false one where Gallo language is spoken, the real Normandy the one of the camp, the false one the one of the field. As a general rule, there is a correlation between « parcels » of identity and linguistic practices. However, on the border, this intellectual order is disrupted since there is a disjunction between criteria that are usually combined. At least between criteria that dialectology and ethnolinguistics have accustomed us to consider as integral: language and culture. The paradox can thus be formulated. On the one hand, people of different languages (Breton language speakers and Gallo language speakers) recognise a common cultural and historical identity. But, on the other hand, people with the same language claim a different identity (Bretons of the border and Normands).