Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota.

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1ß, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

In this study, metabolomics technology and intestinal microbiota 16S rRNA gene sequencing were used to search for biomarkers with significant differences in each stage of pulmonary fibrosis. Finally, the variation characteristics of each stage of the disease were discussed. The hope is to provide new insights into the development of diagnostic biomarkers and potential therapeutic targets at all stages.

[Heavy Metal Pollution and Health Risk Assessment in Karst Basin Around a Lead-Zinc Mine].

Water quality is one of the most important environmental issues in the sustainable development of karst areas. To investigate heavy metal pollution and assess health risk in karst water basins around mines, 18 groups of water samples were collected from the river and groundwater in the Sidi River karst basin, and the concentrations of nine types of heavy metals(Cu, Pb, Zn, Cd, Mn, Fe, As, Cr, and Sr) were determined. Sample data were analyzed using principal component analysis, correlation analysis, water quality index, the Nemerow comprehensive pollution index, hazard quotient, and hazard index. The results showed that the Sidi River was slightly alkaline. The farther the river water samples were from the tailings reservoir, the lower were the concentrations of Cu, Pb, Zn, Cd, Mn, Fe, As, and Sr in the river water. Principal component and correlation analyses showed that heavy metals in the Sidi River karst basin mainly came from mine discharge(55.42%), carbonate weathering dissolution(21.41%), and human activities(14.72%). Eighty-two percent of the samples in the river and all the samples in the groundwater were excellent water. The Nemerow comprehensive pollution index in the river was 4.12 with strong pollution. All the hazard indices were below 1, and Pb, Zn, As, Cd, and Cr were potentially threatening metals in the Sidi River karst basin. The concentration of heavy metals changed significantly after entering the karst conduit, indicating that the unique properties of the karst aquifer affected the spatial variation of the heavy metal concentration. The results of this study can provide data reference for water resource prevention and human health protection in the Sidi River karst basin and similar karst basins.

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment.

BACKGROUND: The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta-analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment. METHODS: A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome. RESULTS: A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post-neoadjuvant treatment and post-surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly. CONCLUSION: Our comprehensive meta-analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

Direct analysis in real-time tandem mass spectrometry method for the rapid screening of 11 new psychoactive substances in blood and urine.

RATIONALE: With the continuous renewal of new psychoactive substances (NPS), the abuse of NPS has seriously harmed social security and public safety. The number of deaths from the abuse of NPS is increasing year by year. Therefore, there is an immediate need to develop an effective method for detecting NPS. METHODS: Direct analysis in real-time tandem mass spectrometry (DART-MS/MS) was used to detect 11 NPS in blood and urine. The temperature of the ion source was optimized and set to 400°C. The mixture solvent of acetonitrile/methanol (4:1, v/v) was used as the precipitant. SKF-525 (2-(diethylamino)ethyl 2,2-diphenylpentanoate) was selected as the internal standard for quantification. After the pretreatment of the analytes in blood or urine, the supernatant was prepared for instrumental analysis. RESULTS: The results indicated that the correlation coefficients (r2 ) of all analytes ranged from 0.99 to 1 in the linear range. The recoveries of 11 analytes at three spiked levels ranged between 83.4% and 110.4% in blood and between 81.7% and 108.5% in urine. The matrix effects of 11 analytes ranged between 79.5% and 109.5% in blood and between 85.0% and 109.4% in urine. The relative standard deviations of intra-day and inter-day precisions and repeatability were lower than 12.4%, 14.1%, and 14.3% in blood and lower than 11.4%, 13.9%, and 14.3% in urine, respectively. CONCLUSION: The method established for the detection of 11 NPS could meet the needs for the rapid screening of NPS samples. The DART-MS/MS method has the advantages of being efficient, fast, and green. Therefore, it may become a promising technology for the detection of NPS in the future.

Trends in Homicide Rates for US Children Aged 0 to 17 Years, 1999 to 2020.

Importance: Homicide is a leading cause of death among children in the US. Objective: To examine trends in child homicide rates and characteristics most commonly associated with these deaths. Design, Setting, and Participants: In this cross-sectional study, the study team used National Vital Statistics System WONDER mortality data for 38 362 homicide victims aged 0 to 17 years for 1999 to 2020 and National Violent Death Reporting System data for child homicide victims for 2003 to 2019 in 45 states, Washington, DC, and Puerto Rico. WONDER data are based on death certificates for US residents. National Violent Death Reporting System data include characteristics of violent deaths, linking information from death certificates, and law enforcement, coroner, and medical examiner reports. Exposures: Child homicide was defined using underlying cause-of-death codes U01 to U02, X85 to Y09, and Y87.1 from the International Classification of Diseases, Tenth Revision, Clinical Modification. Main Outcomes and Measures: Trends in homicide rates per 100 000 children were tested using joinpoint regression analysis; differences in rates from 2019 to 2020 were evaluated using z tests. Circumstances of child homicides were described. Results: This study included 38 362 homicide victims (69.4% male). The overall child homicide rate (per 100 000 children) has increased annually, on average 4.3% since 2013, with a precipitous rise from 2019 to 2020 (2019 rate, 2.2; 2020 rate, 2.8; overall increase of 27.7%). Homicide rates recently increased significantly for boys (2018 rate, 2.9; 2020 rate, 4.1; overall increase of 16.1%), 6- to 10-year-olds (2014 rate, 0.5; 2020 rate, 0.8; overall increase of 5.6%), 11- to 15-year-olds (2018 rate, 1.3; 2020 rate, 2.2; overall increase of 26.9%), 16- to 17-year-olds (2018 rate, 6.6; 2020 rate, 10.0; overall increase of 19.0%), Black children (2012 rate, 5.9; 2018 rate, 6.8; 2020 rate, 9.9; overall increase of 16.6% from 2018 to 2020), Hispanic children (2014 rate, 1.6; 2020 rate, 2.2; overall increase of 4.7%), children in the South (2013 rate, 2.1; 2020 rate, 3.5; overall increase of 6.4%), and in rural (2011 rate, 1.8; 2020 rate, 2.4; overall increase of 3.2%) and urban areas (2013 rate, 1.9; 2020 rate, 2.9; overall increase of 4.4%). Since 1999, homicide rates have decreased for girls (1999 rate, 1.9; 2020 rate, 1.5; overall decrease of 1.4%), infants (1999 rate, 8.7; 2020 rate, 6.6; overall decrease of 1.3%), 1- to 5-year-olds (1999 rate, 2.1; 2020 rate, 1.8; overall decrease of 1.0%), Asian or Pacific Islander children (1999 rate, 2.0; 2020 rate, 0.5; overall decrease of 4.4%), White children (1999 rate, 1.5; 2020 rate, 1.3; overall decrease of 0.7%), and children in the Northeast (1999 rate, 2.0; 2020 rate, 1.7; overall decrease of 1.4%). Homicides of children 10 years or younger were most commonly precipitated by abuse/neglect, perpetrated by parents/caregivers. Homicides of 11- to 17-year-olds were most commonly precipitated by crime and arguments and perpetrated by someone known to them, especially friends and acquaintances. Conclusions and Relevance: The decline in homicide rates for some geographic and child demographic groups is encouraging; however, rates recently increased across several subpopulations, with some racial and ethnic disparities persisting for more than 20 years. More targeted strategies are needed to (1) protect 6- to 10-year-olds, 11- to 17-year-olds, and children in certain geographic areas and (2) urgently address firearm violence, racism, and inequities at the root of youth violence.

Dissolved Heavy Metal Pollution and Assessment of a Karst Basin around a Mine, Southwest China.

Karst water quality is one of the most important environmental issues in karst areas. The study's purpose was to investigate dissolved heavy metal pollution and health risk assessment in karst water basins around mines. River water and groundwater samples were analyzed by principal component analysis, correlation analysis, water quality index, hazard quotient, and hazard index. Median concentrations of dissolved heavy metals in the Sidi River were similar to the world average with a slightly alkaline characteristic. The concentrations of most dissolved heavy metals in river water were higher than those in groundwater. The concentrations of Zn, Pb, and Cd around the mine exceeded the limits of drinking water indicators. The poor water quality samples with high water quality index values were distributed around the mine. Lead (Pb), Zn, As, Cd, and Cr were potentially threatening metals in the study area. The pollution level of dissolved heavy metals in the Sidi River was at a medium level compared with other rivers worldwide. Principal component analysis and correlation analysis showed that Cu, Pb, Zn, Cd, Mn, Fe, As, and Sr mainly came from mine drainage; Ca2+, Mg2+, and Cr mainly came from the contribution of carbonate rocks; Na+ and K+ were related to local human agricultural activities. The concentrations of dissolved heavy metals in groundwater were affected by karst aquifers. The results of this study can provide a data reference for water resources prevention and human health protection in the Sidi River's karst basin and similar karst basins.

Global, regional, national burden and gender disparity of cataract: findings from the global burden of disease study 2019.

BACKGROUND: To evaluate the global burden of cataracts by year, age, region, gender, and socioeconomic status using disability-adjusted life years (DALYs) and prevalence from the Global Burden of Disease (GBD) study 2019. METHODS: Global, regional, or national DALY numbers, crude DALY rates, and age-standardized DALY rates caused by cataracts, by year, age, and gender, were obtained from the Global Burden of Disease Study 2019. Socio-demographic Index (SDI) as a comprehensive indicator of the national or regional development status of GBD countries in 2019 was obtained from the GBD official website. Kruskal-Wallis test, linear regression, and Pearson correlation analysis were performed to explore the associations between the health burden with socioeconomic levels, Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: From 1990 to 2019, global DALY numbers caused by cataracts rose by 91.2%, crude rates increased by 32.2%, while age-standardized rates fell by 11.0%. Globally, age-standardized prevalence and DALYs rates of cataracts peaked in 2017 and 2000, with the prevalence rate of 1283.53 [95% uncertainty interval (UI) 1134.46-1442.93] and DALYs rate of 94.52 (95% UI 67.09-127.24) per 100,000 population, respectively. The burden was expected to decrease to 1232.33 (95% UI 942.33-1522.33) and 91.52 (95% UI 87.11-95.94) by 2050. Southeast Asia had the highest blindness rate caused by cataracts in terms of age-standardized DALY rates (99.87, 95% UI: 67.18-144.25) in 2019. Gender disparity has existed since 1990, with the female being more heavily impacted. This pattern remained with aging among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age-standardized DALYs (equation: Y = -53.2*X + 50.0, P < 0.001) and prevalence rates (equation: Y = - 492.8*X + 521.6, P < 0.001) was negatively correlated with SDI in linear regression. CONCLUSION: The global health of cataracts is improving but the steady growth in crude DALY rates suggested that health progress does not mean fewer demands for cataracts. Globally, older age, females, and lower socioeconomic status are associated with higher cataract burden. The findings of this study highlight the importance to make gender-sensitive health policies to manage global vision loss caused by cataracts, especially in low SDI regions.

Risk factor analysis and clinical decision tree model construction for diabetic retinopathy in Western China.

BACKGROUND: Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. AIM: To build a clinical prediction model that will enable early prevention and treatment of DR. METHODS: In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. RESULTS: Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. CONCLUSION: Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

Identification and assessment of TCR-T cells targeting an epitope conserved in SARS-CoV-2 variants for the treatment of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global public health challenge, with the emergence of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current vaccines or monoclonal antibodies may not well be protect against infection with new SARS-CoV-2 variants. Unlike antibody-based treatment, T cell-based therapies such as TCR-T cells can target epitopes that are highly conserved across different SARS-CoV-2 variants. Reportedly, T cell-based immunity alone can restrict SARS-CoV-2 replication. METHODS: In this study, we identified two TCRs targeting the RNA-dependent RNA polymerase (RdRp) protein in CD8 + T cells. Functional evaluation by transducing these TCRs into CD8 + or CD4 + T cells confirmed their specificity. RESULTS: Combinations of inflammatory and anti-inflammatory cytokines secreted by CD8 + and CD4 + T cells can help control COVID-19 in patients. Moreover, the targeted epitope is highly conserved in all emerged SARS-CoV-2 variants, including the Omicron. It is also conserved in the seven coronaviruses that infect humans and more broadly in the subfamily Coronavirinae. CONCLUSIONS: The pan-genera coverage of mutant epitopes from the Coronavirinae subfamily by the two TCRs highlights the unique strengths of TCR-T cell therapies in controlling the ongoing pandemic and in preparing for the next coronavirus outbreak.

Quantitative assessment of oculomotor function by videonystagmography in multiple system atrophy.

OBJECTIVE: To quantitatively assess oculomotor impairments in multiple system atrophy (MSA) and to explore their correlation with clinical characteristics. METHODS: We recruited 45 patients with MSA, including 21 with dominant ataxia (MSA-C), 24 with dominant parkinsonism (MSA-P), and 40 age-matched healthy controls. Detailed oculomotor performance in the horizontal direction was measured using videonystagmography (VNG). RESULTS: We found that the proportion of abnormal eye movements in patients with MSA was 93.3% (37.7%, 51.1%, 73.3%, 71.1%, and 37.8% on fixation and gaze-holding, without fixation, saccade, smooth pursuit, and optokinetic nystagmus tests, respectively). Patients with MSA-C showed significantly lower gains in smooth pursuit test and optokinetic nystagmus test, and a higher incidence of hypermetria in the saccade test than patients with MSA-P (all P < 0.05). No oculomotor deficits were correlated with age, age of onset, sex, disease duration, or Unified Multiple System Atrophy Rating Scale (USMARS) (all r < 0.25, P > 0.1). CONCLUSIONS: An extremely high incidence of oculomotor impairments could be observed using VNG in both the MSA-C and MSA-P subtypes, although there were some differences between them. SIGNIFICANCE: A comprehensive oculomotor examination could serve as a valuable tool in the diagnostic workup of patients with MSA.

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19.

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public's awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research.

Differences in State Traumatic Brain Injury-Related Deaths, by Principal Mechanism of Injury, Intent, and Percentage of Population Living in Rural Areas - United States, 2016-2018.

Traumatic brain injuries (TBIs) have contributed to approximately one million deaths in the United States over the last 2 decades (1). CDC analyzed National Vital Statistics System (NVSS) mortality data for a 3-year period (2016-2018) to examine numbers and rates of TBI-related deaths, the percentage difference between each state's rate and the overall U.S. TBI-related death rate, leading causes of TBI, and the association between TBI and a state's level of rurality. During 2016-2018, a total of 181,227 TBI-related deaths (17.3 per 100,000 population per year) occurred in the United States. The percentage difference between state TBI-related death rates and the overall U.S. rate during this period ranged from 46.2% below to 101.2% above the overall rate. By state, the lowest rate was in New Jersey (9.3 per 100,000 population per year); the states with the highest rates were Alaska (34.8), Wyoming (32.6), and Montana (29.5). States in the South and those with a higher proportion of residents living in rural areas had higher rates, whereas states in the Northeast and those with a lower proportion of residents living in rural areas had lower TBI-related death rates. In 43 states, suicide was the leading cause of TBI-related deaths; in other states, unintentional falls or unintentional motor vehicle crashes were responsible for the highest numbers and rates of TBI-related deaths. Consistent with previous studies (2), differences in TBI incidence and outcomes were observed across U.S. states; therefore, states can use these findings to develop and implement evidence-based prevention strategies, based on their leading causes of TBI-related deaths. Expanding evidence-based prevention strategies that address TBI-related deaths is warranted, especially among states with high rates due to suicide, unintentional falls, and motor vehicle crashes.

Voxel-Wise Analysis of Structural and Functional MRI for Lateralization of Handedness in College Students.

The brain structural and functional basis of lateralization in handedness is largely unclear. This study aimed to explore this issue by using voxel-mirrored homotopic connectivity (VMHC) measured by resting-state functional MRI (R-fMRI) and gray matter asymmetry index (AI) by high-resolution anatomical images. A total of 50 healthy subjects were included, among them were 13 left-handers, 24 right-handers, and 13 mixed-handers. Structural and R-fMRI data of all subjects were collected. There were significant differences in VMHC among the three groups in lateral temporal-occipital, orbitofrontal, and primary hand motor regions. Meanwhile, there were significant differences in AI that existed in medial prefrontal, superior frontal, and superior temporal regions. Besides, the correlation analysis showed that the closer the handedness score to the extreme of the left-handedness (LH), the stronger the interhemispheric functional connectivity, as well as more leftward gray matter. In general, left/mixed-handedness (MH) showed stronger functional homotopy in the transmodal association regions that depend on the integrity of the corpus callosum, but more variable in primary sensorimotor cortices. Furthermore, the group differences in VMHC largely align with that in AI. We located the specific regions for LH/MH from the perspective of structural specification and functional integration, suggesting the plasticity of hand movement and different patterns of emotional processing.

Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica.

CONTEXT: The petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF). OBJECTIVE: To evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety. RESULTS: The PET LD50 was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect. CONCLUSIONS: These findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application.

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis.

BACKGROUND: The influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child's health and a parent's ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA). METHODS AND FINDINGS: From 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social-emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children's mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children's cognitive and social-emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child's gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social-emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes. CONCLUSIONS: In this study, we observed that improved housing was associated with on-track cognitive development and with on-track social-emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children's physical health but also with broader aspects of healthy child development.

Seven decades towards malaria elimination in Yunnan, China.

BACKGROUND: Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People's Democratic Republic, Myanmar, and Viet Nam. METHODS: Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). RESULTS: A malaria elimination campaign in the 1950-1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the '1-3-7' surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. CONCLUSIONS: Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.

Clinical practice guidelines for the nutritional risk screening and assessment of cancer patients: a systematic quality appraisal using the AGREE II instrument.

PURPOSE: To evaluate the quality of published clinical practice guidelines (CPGs) regarding the nutritional risk screening and assessment of cancer patients and to identify high-quality CPGs for clinical healthcare professionals. METHODS: Guidelines for the nutritional risk screening and assessment of cancer patients were comprehensively searched in eight electronic databases, including The Lancet, PubMed, Cochrane Library, Excerpta Medica dataBASE (EMBASE), Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), and Wan Fang Data, through August 2020. Six relevant guideline databases, including the National Comprehensive Cancer Network (NCCN), the National Guideline Clearinghouse (NGC), the Guideline International Network (GIN), the New Zealand Guidelines Group (NZGG), the China Guideline Clearinghouse (CGC), and Medlive, and relevant nutrition society websites, were also searched through August 2020. The methodological quality of the included CPGs was appraised independently by three assessors using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II) tool. RESULTS: Seven CPGs were located, and the domain with the highest percentage was "clarity of presentation" (85.44%), while the domain with the lowest percentage was "applicability" (40.26%). From the AGREE II results, two guidelines were rated as "strongly recommended," three were assessed as "recommended with modifications," and two were deemed as "not recommended." CONCLUSION: Considering that the two "strongly recommended" guidelines were developed within the American and European contexts, translation, validation, and cultural adaptation are recommended prior to implementing these guidelines in other countries or healthcare contexts to improve their effectiveness and sensitivity for local cancer patients. TRIAL REGISTRATION: PROSPERO registration of the study protocol: CRD42020177390 (July 5, 2020).

[Seasonal Distribution Characteristics and Health Risk Assessment of Heavy Metals in Surface Water of Qingjiang River].

In order to assess the health risks of heavy metals in surface water of Qingjiang River, surface water samples were taken at designed cross-sections of the river and analyzed for Cr, Cu, Zn, Pb, Cd, As, and Mn. Health risks from these heavy metals for adults and children in wet and dry seasons were compared by water environmental health risk assessment model of the USEPA. It found that the main excessive element is Mn, concentrating in the Danshui, Yantouxi, and Pingluoxi, the slightly excessive element is As, the concentration of Mn was above national standard, and it mainly distributed in Danshui, Yantouxi, and Pingluoxi, As was slightiy over the standard, and it concentrated in Wujiahe, The content of heavy metals during wet season were all higher than those during dry season. Cr, Cu, Zn, and Cd are mainly originated from the nature, Pb and As are separately mainly originated from traffic and agriculture, Mn originated from mining mainly in the downstream, while it has natural source from upper to middle. The health risks of heavy metals in surface water to adults and children in wet season are higher than those in dry season. The main health risk area was the midstream. As was the highest health risk element and children were the most preventive group. Specially, people in towns who drink the water from midstream should pay more attention.

A National Comparison of Operative Outcomes of New and Experienced Surgeons.

OBJECTIVE: To determine whether outcomes achieved by new surgeons are attributable to inexperience or to differences in the context in which care is delivered and patient complexity. BACKGROUND: Although prior studies suggest that new surgeon outcomes are worse than those of experienced surgeons, factors that underlie these phenomena are poorly understood. METHODS: A nationwide observational tapered matching study of outcomes of Medicare patients treated by new and experienced surgeons in 1221 US hospitals (2009-2013). The primary outcome studied is 30-day mortality. Secondary outcomes were examined. RESULTS: In total, 694,165 patients treated by 8503 experienced surgeons were matched to 68,036 patients treated by 2119 new surgeons working in the same hospitals. New surgeons' patients were older (25.8% aged ≥85 vs 16.3%,P<0.0001) with more emergency admissions (53.9% vs 25.8%,P<0.0001) than experienced surgeons' patients. Patients of new surgeons had a significantly higher baseline 30-day mortality rate compared with patients of experienced surgeons (6.2% vs 4.5%,P<0.0001;OR 1.42 (1.33, 1.52)). The difference remained significant after matching the types of operations performed (6.2% vs 5.1%, P<0.0001; OR 1.24 (1.16, 1.32)) and after further matching on a combination of operation type and emergency admission status (6.2% vs 5.6%, P=0.0007; OR 1.12 (1.05, 1.19)). After matching on operation type, emergency admission status, and patient complexity, the difference between new and experienced surgeons' patients' 30-day mortality became indistinguishable (6.2% vs 5.9%,P=0.2391;OR 1.06 (0.97, 1.16)). CONCLUSIONS: Among Medicare beneficiaries, the majority of the differences in outcomes between new and experienced surgeons are related to the context in which care is delivered and patient complexity rather than new surgeon inexperience.

Assessment of whether the rabbit subscapularis tendon model is suitable for studying the human chronic rotator cuff pathology: Discovery of a new ligament connecting the glenoid and subscapularis tendon.

OBJECTIVE: This study aimed to investigate the anatomical relationship between the subscapularis tendon and glenosubscapularal ligament (GSL) that we accidentally identified from our previous study on a rabbit shoulder model and to determine whether this anatomical relationship has an impact on the rabbit shoulder model for studying the human chronic rotator cuff pathology. METHODS: In this study, 15 male New Zealand rabbits aged 12 weeks and weighing 2.5 kg were used. Moreover, 3 rabbits were sacrificed for the anatomical and histological investigation of the relationship between the subscapularis tendon and GSL at baseline. The remaining 12 rabbits underwent the subscapularis tendon tenotomy from the lesser tuberosity using a standardized procedure. The GSL was cut on the left side and preserved on the right side. For histomorphometric analysis, 6 rabbits were first sacrificed at 6 weeks and then the remaining 6 rabbits at 12 weeks. RESULTS: In all the rabbits, GSL was identified, connecting the upper portion of glenoid and subscapularis muscle-tendon junction. The mean thickness of the middle portion of GSL was 1.1±0.2 mm; the mean length of GSL was 8.4±2.3 mm. The mean widths of the proximal and distal attachments were 2.4±0.3 and 4.2±0.5 mm, respectively. The mean size of the native subscapularis muscle fibers was 122.6±4.3 µm2. The mean size of the muscle fibers in shoulders with tenotomy alone was 112.6±6.2 and 102.6±4.8 µm2 at 6 and 12 weeks, respectively. The mean size of the muscle fibers in shoulders with tenotomy plus GSL cut severing was 88.3±9.7 and 56.4±5.2 µm2 at 6 and 12 weeks, respectively. The significant muscle atrophy was observed both at 6 and 12 weeks in the shoulders with tenotomy plus GSL cut compared with those with tenotomy alone as well as those with the native subscapularis. However, the muscle atrophy was not significantly different in the shoulders with tenotomy alone at different time points. CONCLUSION: Because GSL may prevent the subscapularis retraction, the rabbit subscapularis tendon model may not be suitable for studying the human chronic rotator cuff pathology if GSL is neglected or preserved.