[Spatial and Temporal Distribution Characteristics of Ozone Concentration and Health Benefit Assessment in the Beijing-Tianjin-Hebei Region from 2015 to 2020].

To evaluate the spatial and temporal distribution characteristics of ambient ozone (O3) in the Beijing-Tianjin-Hebei (BTH) Region, the land use regression (LUR) model and random forest (RF) model were used to simulate the ambient O3 concentration from 2015 to 2020. Meanwhile, all-cause, cardiovascular, and respiratory mortalities as well as economic losses attributed to O3 were also estimated. The results showed that upward trends with fluctuation were observed for ambient O3 concentration, mortalities, and economic losses attributable to O3 exposure in the BTH Region from 2015 to 2020. The areas with high O3 concentration and great changes were concentrated in the central and southwestern regions, whereas the concentration in the northern region was low, and the change degree was small. The spatial distribution of the mortalities was also consistent with the spatial distribution of O3 concentration. From 2015 to 2020, the economic losses regarding all-cause mortality and cardiovascular mortality increased in 13 cities of the BTH Region, whereas the economic losses of respiratory mortality decreased in 4 cities in the BTH Region. The results indicated that the priority areas for O3 control were not uniform. Specifically, Beijing, Tianjin, Hengshui, and Xingtai were vital areas for O3 pollution control in the BTH Region. Differentiated control measures should be adopted based on the characteristics of these target areas to decline O3 concentration and reduce health impacts and economic losses associated with O3 exposure.

Assessment of Upper Extremity Function in Multiple Sclerosis: Feasibility of a Digital Pinching Test.

BACKGROUND: The development of touchscreen-based assessments of upper extremity function could benefit people with multiple sclerosis (MS) by allowing convenient, quantitative assessment of their condition. The Pinching Test forms a part of the Floodlight smartphone app (F. Hoffmann-La Roche Ltd, Basel, Switzerland) for people with MS and was designed to capture upper extremity function. OBJECTIVE: This study aimed to evaluate the Pinching Test as a tool for remotely assessing upper extremity function in people with MS. METHODS: Using data from the 24-week, prospective feasibility study investigating the Floodlight Proof-of-Concept app for remotely assessing MS, we examined 13 pinching, 11 inertial measurement unit (IMU)-based, and 13 fatigability features of the Pinching Test. We assessed the test-retest reliability using intraclass correlation coefficients [second model, first type; ICC(2,1)], age- and sex-adjusted cross-sectional Spearman rank correlation, and known-groups validity (data aggregation: median [all features], SD [fatigability features]). RESULTS: We evaluated data from 67 people with MS (mean Expanded Disability Status Scale [EDSS]: 2.4 [SD 1.4]) and 18 healthy controls. In this cohort of early MS, pinching features were reliable [ICC(2,1)=0.54-0.81]; correlated with standard clinical assessments, including the Nine-Hole Peg Test (9HPT) (|r|=0.26-0.54; 10/13 features), EDSS (|r|=0.25-0.36; 7/13 features), and the arm items of the 29-item Multiple Sclerosis Impact Scale (MSIS-29) (|r|=0.31-0.52; 7/13 features); and differentiated people with MS-Normal from people with MS-Abnormal (area under the curve: 0.68-0.78; 8/13 features). IMU-based features showed similar test-retest reliability [ICC(2,1)=0.47-0.84] but showed little correlations with standard clinical assessments. In contrast, fatigability features (SD aggregation) correlated with 9HPT time (|r|=0.26-0.61; 10/13 features), EDSS (|r|=0.26-0.41; 8/13 features), and MSIS-29 arm items (|r|=0.32-0.46; 7/13 features). CONCLUSIONS: The Pinching Test provides a remote, objective, and granular assessment of upper extremity function in people with MS that can potentially complement standard clinical evaluation. Future studies will validate it in more advanced MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02952911; https://clinicaltrials.gov/study/NCT02952911.

Digital measures of respiratory and upper limb function in spinal muscular atrophy: design, feasibility, reliability, and preliminary validity of a smartphone sensor-based assessment suite.

Spinal muscular atrophy (SMA) is characterized by progressive muscle weakness and paralysis. Motor function is monitored in the clinical setting using assessments including the 32-item Motor Function Measure (MFM-32), but changes in disease severity between clinical visits may be missed. Digital health technologies may assist evaluation of disease severity by bridging gaps between clinical visits. We developed a smartphone sensor-based assessment suite, comprising nine tasks, to assess motor and muscle function in people with SMA. We used data from the risdiplam phase 2 JEWELFISH trial to assess the test-retest reliability and convergent validity of each task. In the first 6 weeks, 116 eligible participants completed assessments on a median of 6.3 days per week. Eight of the nine tasks demonstrated good or excellent test-retest reliability (intraclass correlation coefficients >0.75 and >0.9, respectively). Seven tasks showed a significant association (P < 0.05) with related clinical measures of motor function (individual items from the MFM-32 or Revised Upper Limb Module scales) and seven showed significant association (P < 0.05) with disease severity measured using the MFM-32 total score. This cross-sectional study supports the feasibility, reliability, and validity of using smartphone-based digital assessments to measure function in people living with SMA.

Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost.

Twenty-nine years following the breakthrough discovery that a single-gene mutation of daf-2 doubles Caenorhabditis elegans lifespan, it remains unclear where this insulin/IGF-1 receptor gene is expressed and where it acts to regulate ageing. Using knock-in fluorescent reporters, we determined that daf-2 and its downstream transcription factor daf-16 are expressed ubiquitously. Using tissue-specific targeted protein degradation, we determined that intracellular DAF-2-to-DAF-16 signaling in the intestine plays a major role in lifespan regulation, while that in the hypodermis, neurons, and germline plays a minor role. Notably, intestine-specific loss of DAF-2 activates DAF-16 in and outside the intestine, causes almost no adverse effects on development and reproduction, and extends lifespan by 94% in a way that partly requires non-intestinal DAF-16. Consistent with intestine supplying nutrients to the entire body, evidence from this and other studies suggests that altered metabolism, particularly down-regulation of protein and RNA synthesis, mediates longevity by reduction of insulin/IGF-1 signaling.

Transmission and mortality risk assessment of severe fever with thrombocytopenia syndrome in China: results from 11-years' study.

BACKGROUND: The transmission and fatal risk of severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease first discovered in China in 2009, still needed further quantification. This research aimed to analyze the SFTS clusters and assess the transmission and mortality risk for SFTS. METHODS: Both epidemiological investigation and case reports regarding SFTS clusters in China during 2011-2021 were obtained from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention Information System. The transmission risk was evaluated by using the secondary attack rate (SAR) and relative risk (RR). Mortality risk factors were analyzed using a logistic regression model. RESULTS: There were 35 SFTS clusters during 2011-2021 involving 118 patients with a fatality rate of 22.0%. The number of clusters annually increased seasonally from April to September. The clusters mainly occurred in Anhui (16 clusters) and Shandong provinces (8 clusters). The SAR through contact with blood or bloody fluids was much higher than that through contact with non-bloody fluids (50.6% vs 3.0%; χ2 = 210.97, P < 0.05), with an RR of 16.61 [95% confidence interval (CI): 10.23-26.97]. There was a statistically significant difference in the SAR between exposure to the blood of a deceased person during burial preparation and exposure to the living patients' blood (66.7% vs 34.5%; χ2 = 6.40, P < 0.05), with an RR of 1.93 (95% CI: 1.11-3.37). The mortality risk factors were a long interval from onset to diagnosis [odds ratio (OR) = 1.385), 95% CI: 1.083-1.772, P = 0.009) and advanced age (OR: 1.095, 95% CI: 1.031-1.163, P = 0.01). CONCLUSIONS: The SFTS clusters showed a high mortality rate and resulted in a high SAR. Contact with a bleeding corpse was associated with a higher infection risk, compared with contacting the blood from living patients. It is important to promote early detection and appropriate case management of patients with SFTS, as well as improved handling of their corpses, to prevent further transmission and mortality.

Research on the Establishment and Application of the Environmental Health Indicator System of Atmospheric Pollution in China.

To understand the health impact represented by exposure to current atmospheric pollution in China, an environmental health indicators (EHIs) system of atmospheric pollution was established. The EHIs were based on comprehensive consideration of environment, population, economy and diseases associated with atmospheric pollution. An EHIs evaluation system of atmospheric pollution, based on corresponding EHIs data collection and weighting coefficients determined using principal component analysis, was applied to major provinces and regions in China to evaluate the environmental health status. Results showed that the EHIs of atmospheric pollution in Central and East China were low, indicating a serious environmental health condition. Prevention and management of atmospheric pollution in these regions should be strengthened and protective measures taken to improve human health. Compared with other methods, the EHIs evaluation system was more intuitive, which facilitated users to identify the environmental health status and provided support for health management and pollution prevention.

A nationwide survey on neonatal medical resources in mainland China: current status and future challenges.

BACKGROUND: With the rapid development of economy in recent two decades, neonatology has been progressing quickly in China. However, there is little knowledge about the exact developmental status of neonatal departments in China. The aim of this study was to assess resources available for care of sick newborns in mainland China. METHODS: Questionnaires were sent to the membership of the Chinese Neonatologist Association (CNA) and used to survey the scale, facilities, staff, technologies, transport systems and preterm infants' outcomes of neonatal departments (NDs) in different areas of China from June 2012 to December 2012. RESULTS: The result of this survey including a total of 117 questionnaires showed that investigated ND had a mean of 65 (median 47; range 5-450) beds, including 19.59 (median 15, range 0-100) NICU beds. The overall doctor/bed and nurse/bed ratio was 1:3.84 and 1:1.43, respectively. Lack of medical equipment was one of the main problems in most NDs surveyed, and only 26 NDs (22.2%) had more than one neonatal incubator per bed. Only 70.1, 30.6, 30.8 and 4.3% NDs carried out high-frequency ventilation, hypothermia, nitric oxide inhalation, and ECMO respectively. The capacity to provide advanced therapies increased with the size of the NDs (P < .01). A total of 81 NDs (69.2%) carried out neonatal transport, but only 70 NDs (86.4%) were equipped with transport incubators, 36 NDs (44.4%) had the ability of performing intrauterine transport of the preterm infants, and 3 NDs (3.7%) had the ability of performing air transport. The survival rate of extremely preterm infants (Gestational age less than 28w) to discharge home was 47.8% in 2011. CONCLUSION: NDs in mainland China are not well distributed and still face many problems, such as staff shortage, inadequate facilities, and imperfect transport. It is urgent to set up a classification of neonatal care to enhance the utilization rate of medical resources and improve the prognosis of critically ill infants.

Assessment of Acute Motor Effects and Tolerance Following Self-Administration of Alcohol and Edible ∆9 -Tetrahydrocannabinol in Adolescent Male Mice.

BACKGROUND: Cannabinoids and their principle psychoactive target, the cannabinoid type 1 receptor (CB1R), impact a number of alcohol-related properties, and although alcohol and cannabis are often co-used, particularly in adolescence, few animal models of this phenomenon exist. We modeled the co-use of alcohol and ∆9 -tetrahydrocannabinol (THC) in adolescent mice using ingestive methods popular during this developmental period in humans, namely binge-drinking and edible THC. With this model, we assessed levels of use, acute effects, and tolerance to each substance. METHODS: Adolescent male C57BL/6J mice had daily, limited access to 1 of 2 edible doughs (THC or control), to 1 of 2 fluids (ethanol (EtOH) or water), and in 1 of 2 orders (dough-fluid or fluid-dough). Home cage locomotor activity was recorded both during access and after access. On the day following the final access session, a subset of mice were assessed for functional and metabolic tolerance to alcohol using accelerating rotarod and blood EtOH concentrations, respectively. The remaining mice were assessed for tolerance to THC-induced hypothermia, and whole-brain CB1R expression was assessed in all mice. RESULTS: EtOH intake was on par with levels previously reported in adolescent mice. Edible THC was well-consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following EtOH intake and decreased following edible THC consumption, and edible THC increased fluid intake in general. The use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, the use of edible THC impaired subsequent drug-free rotarod performance and was associated with a reduction in THC's hypothermic effect. CONCLUSIONS: Adolescent mice self-administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short-term abstinence. Thus, this adolescent co-use model could be used to explore sex differences in self-administration and the impact substance co-use might have on other domains such as mood and cognition.

Production of fuels and chemicals from renewable resources using engineered Escherichia coli.

Biotechnological production of fuels and chemicals from renewable resources is an appealing way to move from the current petroleum-based economy to a biomass-based green economy. Recently, the feedstocks that can be used for bioconversion or fermentation have been expanded to plant biomass, microbial biomass, and industrial waste. Several microbes have been engineered to produce chemicals from renewable resources, among which Escherichia coli is one of the best studied. Much effort has been made to engineer E. coli to produce fuels and chemicals from different renewable resources. In this paper, we focused on E. coli and systematically reviewed a range of fuels and chemicals that can be produced from renewable resources by engineered E. coli. Moreover, we proposed how can we further improve the efficiency for utilizing renewable resources by engineered E. coli, and how can we engineer E. coli for utilizing alternative renewable feedstocks. e.g. C1 gases and methanol. This review will help the readers better understand the current progress in this field and provide insights for further metabolic engineering efforts in E. coli.

p32 heterozygosity protects against age- and diet-induced obesity by increasing energy expenditure.

Obesity is increasing in prevalence and has become a global public health problem. The main cause of obesity is a perturbation in energy homeostasis, whereby energy intake exceeds energy expenditure. Although mitochondrial dysfunction has been linked to the deregulation of energy homeostasis, the precise mechanism is poorly understood. Here, we identify mitochondrial p32 (also known as C1QBP) as an important regulator of lipid homeostasis that regulates both aerobic and anaerobic energy metabolism. We show that while whole-body deletion of the p32 results in an embryonic lethal phenotype, mice heterozygous for p32 are resistant to age- and high-fat diet-induced ailments, including obesity, hyperglycemia, and hepatosteatosis. Notably, p32 +/- mice are apparently healthy, demonstrate an increased lean-to-fat ratio, and show dramatically improved insulin sensitivity despite prolonged high-fat diet feeding. The p32 +/- mice show increased oxygen consumption and heat production, indicating that they expend more energy. Our analysis revealed that haploinsufficiency for p32 impairs glucose oxidation, which results in a compensatory increase in fatty acid oxidation and glycolysis. These metabolic alterations increase both aerobic and anaerobic energy expenditure. Collectively, our data show that p32 plays a critical role in energy homeostasis and represents a potential novel target for the development of anti-obesity drugs.

In vivo assessment of dermal adhesion, penetration, and bioavailability of tetrabromobisphenol A.

Individuals are exposed to brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), on a daily basis because of their widespread usage. These compounds may have adverse effects on human health. In the present study, dermal absorption experiments were conducted in vivo to predict the adhesion, penetration, and bioavailability of TBBPA. TBBPA was administered to Wistar rats for 6 h by repeated dermal exposure at doses of 20, 60, 200, and 600 mg of TBBPA per kg of body weight (bw). The skin adhesion coefficient (AC) was calculated using a difference-value method and ranged from 0.12 to 3.25 mg/cm2 and 0.1 to 2.56 mg/cm2 for the male and female rats, respectively. The adhesion rate was 70.92%. According to Fick's first law of diffusion, the diffusion constant (D) was 1.4 × 10-4 cm2/h and the permeation coefficient (Kp) was 1.26 × 10-5 cm/h for TBBPA. TBBPA levels in the blood, urine, and feces of the male rats were significantly higher than those in the female rats. The dermal bioavailability of TBBPA was 24.71% for male rats and 20.05% for female rats 24 h after exposure.

Protection against High-Fat-Diet-Induced Obesity in MDM2C305F Mice Due to Reduced p53 Activity and Enhanced Energy Expenditure.

The RPL11-MDM2 interaction constitutes a p53 signaling pathway activated by deregulated ribosomal biosynthesis in response to stress. Mice bearing an MDM2C305F mutation that disrupts RPL11-MDM2 binding were analyzed on a high-fat diet (HFD). The Mdm2C305F/C305F mice, although phenotypically indistinguishable from wild-type (WT) mice when fed normal chow, demonstrated decreased fat accumulation along with improved insulin sensitivity and glucose tolerance after prolonged HFD feeding. We found that HFD increases expression of c-MYC and RPL11 in both WT and Mdm2C305F/C305F mice; however, p53 was induced in WT but not in Mdm2C305F/C305F mice. Reduced p53 activity in HFD-fed Mdm2C305F/C305F mice resulted in higher levels of p53 downregulated targets GLUT4 and SIRT1, leading to increased biosynthesis of NAD+, and increased energy expenditure. Our study reveals a role for the RPL11-MDM2-p53 pathway in fat storage during nutrient excess and suggests that targeting this pathway may be a potential treatment for obesity.

IHC4 score plus clinical treatment score predicts locoregional recurrence in early breast cancer.

PURPOSE: Immunohistochemical 4 (IHC4) score plus Clinical Treatment Score (CTS) is an inexpensive tool predicting risk of distant recurrence in women with early breast cancer (EBC). IHC4 score is based on ER, PR, HER2 and Ki67 index. This study explores the role of the combined score (IHC4 + CTS) in predicting risk of locoregional recurrence (LRR) in women with EBC who had breast conservation surgery (BCS) without adjuvant radiotherapy (study group). The secondary objective was to evaluate the clinicopathological differences between our study group and women who had adjuvant radiation following BCS (control group). METHODS AND MATERIALS: Patients were selected from the local database over a 13-year period. IHC testing was done where results were missing. Combined scores were calculated using the appropriate formulae. RESULTS: Patients in the study group (81 patients) had favorable clinicopathological features compared to the control group (1406 patients). The Cox regression indicated a statistically significant association between the combined score and the risk of LRR (p = 0.03). The incidence of LRR was zero, 20% and 33.3% in the low, intermediate and high risk groups respectively (p = 0.007). Margin status was the only variable not included in the combined score. The Cox regression analysis demonstrated that the combined score (p = 0.02) and the ordinal measure of margins (p = 0.03) were significant independent predictors of LRR. CONCLUSION: This is the first study of its kind. The IHC4 score + CTS can be used to identify low risk women who can potentially avoid adjuvant radiotherapy.

[The prevalence characteristic and prevention strategy of Japanese B Encephalitis in Henan province].

OBJECTIVE: To analyze the prevalence trend, prevalence characteristics and influence factors of Japanese B Encephalitis (JE) in Henan province. METHODS: The data that of 64 401 JE patients in Henan from 1980 to 2008 were statistically analyzed by SPSS12.0 and EXCEL2003 software. Luoshan, Xinan, Xihua, Deng county and Hua county were chosen as monitoring sites. The mosquito specimens were gathered with the artificial hour method and the mosquito curtain method, the mosquito density was calculated one time each ten day period from May to July. At the same time, 30-40 newborn pig blood samples were gathered each ten-day period and the pig serum JE IgG antibody was detected by ELISA method. RESULTS: The Cumulative incidence of JE was 64 401 cases in Henan province from 1998 to 2008, the range of incidence rate was from 0.34/100 000 (315/93 599 969) to 6.72/100 000 (5246/78 076 567); The average incidence of JE was 4.39/100 000 (3530/80 381 469) from 1980 to 1994; The average incidence of JE was 0.86/100 000 (811/94 217 549) from 1995 to 2008; In 2008, the incidence rate reached the lowest point for 0.34/100 000 (315/93 599 969); The incidence occurred mainly in July-September, accounting for 89.40% of the total cases (57 572/64 401); the patients were concentrated mainly in 5 cities, which were Xinyang, Nanyang, Zhumadian, Zhoukou, Luoyang, accounting for 81.02% (52 175/64 401). The 0 - 14 years old age group was the dominant group (79.01%, 50 884/64 401). In Luoyang city, incidence of >/= 15 years old group was significantly increased (57.83%, 2120/3666), the constitution of JE incidence were significantly different between 0 - 14 years old group and >/= 15 years old age group (chi(2) = 2705.32, P < 0.05) in Henan province and Luoyang city. The different density of the mosquitoes and the different positive-times for 50% of the antibodies of JE in piglets on the monitor sites showed the intensity of JE disease. CONCLUSION: The incidence of JE showed a decreasing trend, seasonal, regional characteristics and age distribution difference in Henan province. The monitoring of host animal pig JE antibody level and the medium mosquito density may forecast the JE prevalence tendency. To control the incidence in the younger groups in Henan province, older age group in Luoyang city and high-incidence areas, it is important to strengthen the monitoring and forecasting measures to prevent JE in Henan province.

Risk factors for suicide in China: a national case-control psychological autopsy study.

BACKGROUND: Suicide is the fifth most important cause of death in China, but the reasons for the high rate and unique pattern of characteristics of those who kill themselves are unknown. METHODS: We pretested, and then administered a comprehensive interview to family members and close associates of 519 people who committed suicide and of 536 people who died from other injuries (controls) randomly selected from 23 geographically representative sites in China. FINDINGS: After adjustment for sex, age, location of residence, and research site, eight significant predictors of suicide remained in the final unconditional logistic regression model. In order of importance they were: high depression symptom score, previous suicide attempt, acute stress at time of death, low quality of life, high chronic stress, severe interpersonal conflict in the 2 days before death, a blood relative with previous suicidal behaviour, and a friend or associate with previous suicidal behaviour. Suicide risk increased substantially with exposure to multiple risk factors: none of the 265 deceased people who were exposed to one or fewer of the eight risk factors died by suicide, but 30% (90/299) with two or three risk factors, 85% (320/377) with four or five risk factors, and 96% (109/114) with six or more risk factors died by suicide. INTERPRETATION: Despite substantial differences between characteristics of people who commit suicide in China and the west, risk factors for suicide do not differ greatly. Suicide prevention programmes that concentrate on a single risk factor are unlikely to reduce suicide rates substantially; preventive efforts should focus on individuals exposed to multiple risk factors.