Publications by authors named "Lin Shao"

320 Publications

The Efficacy of Combined Cisplatin and Nanoparticle Albumin-Bound Paclitaxel in a Stage IV Pancreatic Squamous Cell Carcinoma Patient With a Somatic Mutation: A Case Report.

Front Oncol 2021 29;11:585983. Epub 2021 Apr 29.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with -mutant pancreatic SCC.
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http://dx.doi.org/10.3389/fonc.2021.585983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116796PMC
April 2021

Significant Benefits of Afatinib and Apatinib in a Refractory Advanced NSCLC Patient Resistant to Osimertinib: A Case Report.

Onco Targets Ther 2021 7;14:3063-3067. Epub 2021 May 7.

Department of Respiratory Disease, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, People's Republic of China.

EGFR-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for NSCLC. However, acquired drug resistance often occurs after treatment with EGFR-TKIs. T790M and C797S mutations are the most common resistance mechanism in patients who failed from first- and third- generation EGFR TKI treatments, respectively. However, there is no standard of care for NSCLC harboring T790M and C797S in-cis. The present case reports a 69-year-old Chinese man with advanced NSCLC harboring exon 19-deletion, T790M, cis-C797S, and amplification who was heavily pre-treated. The patient was then given a combination of afatinib and apatinib and achieved a PFS of more than 10 months. This case showed that afatinib plus apatinib may be a promising therapy for patients with 19Del-T790M-cis-C797S mutant and amplified NSCLC.
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http://dx.doi.org/10.2147/OTT.S300556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114361PMC
May 2021

Combination of Osimertinib and Anlotinib May Overcome the Resistance Mediated by in cis T790M-C797S in NSCLC: A Case Report.

Onco Targets Ther 2021 28;14:2847-2851. Epub 2021 Apr 28.

Department of Hematology and Oncology, The 904 Hospital of the PLA (Chinese People's Liberation Army), Wuxi, People's Republic of China.

The emergence of epidermal growth factor receptor () exon 20 p.C797S is one of the major resistance mechanisms for osimertinib. However, there are no standard of care for non-small cell lung cancer (NSCLC) patients after acquiring C797S currently, which brings significant challenges to post-osimertinib clinical management. In the present study, we described a 52-year-old female patient with -mutated stage IV lung adenocarcinoma, who achieved a partial response (PR) to the treatment of gefitinib and osimertinib after acquiring exon 20 p.T790M-trans-C797S at osimertinib failure. After progression on the combinatorial treatment, allelic configuration shifted to T790M-cis-C797S. The patient subsequently received a regimen of osimertinib and anlotinib combined with chemotherapy, followed by osimertinib and anlotinib maintenance treatment, and achieved a PR lasting for 9 months. At disease progression, concomitant T790M-C797S mutations both in trans and cis were identified. A combination of chemo- and anti-angiogenic therapies was administrated for two cycles and then discontinued because of the poor physical condition of the patient. She passed away soon with an overall survival of 39 months and a post-osimertinib progression survival of 20 months. Our study provides the first clinical evidence that the osimertinib and anlotinib-based regimen may be an effective therapy in overcoming resistance mediated by T790M-cis-C797S. Our case also highlights the importance of dynamically monitoring the mutation status after osimertinib failure, which may provide patients with increased opportunities for targeted therapy and improve post-osimertinib progression survivals.
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http://dx.doi.org/10.2147/OTT.S298655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093742PMC
April 2021

Predicting environmental risk factors in relation to health outcomes among school children from Romania using random forest model - An analysis of data from the SINPHONIE project.

Sci Total Environ 2021 Aug 16;784:147145. Epub 2021 Apr 16.

Health Department, Environmental Health Center, 58 Busuiocului Street, Cluj-Napoca, Romania; Faculty of Environmental Science and Engineering, Babes-Bolyai University, 30 Fantanele Street, Cluj-Napoca, Romania; Cluj School of Public Health - College of Political, Administrative and Communication Sciences, Babes-Bolyai University, Cluj-Napoca, Romania.

Background: Few studies have simultaneously assessed the health impact of school and home environmental factors on children, since handling multiple highly correlated environmental variables is challenging. In this study, we examined indoor home and school environments in relation to health outcomes using machine learning methods and logistic regression.

Methods: We used the data collected by the SINPHONIE (Schools Indoor Pollution and Health: Observatory Network in Europe) project in Romania, a multicenter European research study that collected comprehensive information on school and home environments, health symptoms in children, smoking, and school policies. The health outcomes were categorized as: any health symptoms, asthma, allergy and flu-like symptoms. Both logistic regression and random forest (RF) methods were used to predict the four categories of health outcomes, and the methods prediction performance was compared.

Results: The RF method we employed for analysis showed that common risk factors for the investigated categories of health outcomes, included: environmental tobacco smoke (ETS), dampness in the indoor school environment, male gender, air freshener use, residence located in proximity of traffic (<200 m), stressful schoolwork, and classroom noise (contributions ranged from 7.91% to 23.12%). Specificity, accuracy and area under the curve (AUC) values for most outcomes were higher when using RF compared to logistic regression, while sensitivity was similar in both methods.

Conclusion: This study suggests that ETS, dampness in the indoor school environment, use of air fresheners, living in proximity to traffic (<200 m) and noise are common environmental risk factors for the investigated health outcomes. RF pointed out better predictive values, sensitivity and accuracy compared to logistic regression.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147145DOI Listing
August 2021

Concomitant mutation status of -rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib.

Transl Lung Cancer Res 2021 Mar;10(3):1525-1535

Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin, China.

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase () rearrangement characterizes a subgroup of patients who show sensitivity to tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients.

Methods: We retrospectively analyzed 96 patients with NSCLC with detected by immunohistochemical staining (VENTANA anti-(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed.

Results: Among the 96 patients with immunohistochemically identified fusions, 80 (83%) were confirmed by next-generation sequencing. mutation was the most commonly co-occurring mutation with rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog () G12, 1 epidermal growth factor receptor () 19del, and 1 exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 ()- fusions were identified in 95% of -rearranged patients, with 16.2% of them also harboring additional non-- fusions. Nineteen non- translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring alterations showed a trend toward shorter progression-free survival (6 13 months, P=0.064) and significantly shorter overall survival (11 32 months, P=0.004) than did -wild-type patients. Patients with concomitant alterations in the signaling pathway also had a shorter median overall survival than those without such alterations (23 32 months, P=0.014), whereas progression-free survival did not differ significantly.

Conclusions: The spectrum of -fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of -rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy.
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http://dx.doi.org/10.21037/tlcr-21-160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044492PMC
March 2021

Gestational exposure to perfluoroalkyl substances and congenital heart defects: A nested case-control pilot study.

Environ Int 2021 Apr 23;154:106567. Epub 2021 Apr 23.

Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, #96 Dongchuan Road, Guangzhou 510080, China. Electronic address:

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs.

Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables.

Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood.

Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.
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http://dx.doi.org/10.1016/j.envint.2021.106567DOI Listing
April 2021

Rapid Disease Progression in a Patient with Advanced NSCLC Harboring a Germline Exon 14 Skipping Mutation: A Case Report.

Onco Targets Ther 2021 7;14:2417-2421. Epub 2021 Apr 7.

Pulmonary and Critical Care Medicine, Changhai Hospital, The Naval Medical University, Guangzhou, People's Republic of China.

exon 14 skipping variants have been identified as a novel type of oncogenic driver mutations in non-small-cell lung cancer (NSCLC), while the germline mutation, especially germline exon 14 skipping mutation rarely occurred in NSCLC. Herein, we present the first case of a 33-year-old NSCLC patient with a germline exon 14 skipping mutation, who also harbored a somatic exon 20 insertion. The patient was initially diagnosed with a stage IIB adenosquamous carcinoma. He underwent a thoracoscopic radical resection followed by four cycles of adjuvant chemotherapy but relapsed 2 months after completing the chemotherapy. Afatinib was then prescribed but disease progressed immediately. Subsequently, he received anlotinib but did not respond and died a month later with an overall survival of 9 months. Our case may provide an evidence for the pathogenicity of germline exon 14 skipping mutation in NSCLC and suggest it as an adverse prognostic factor.
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http://dx.doi.org/10.2147/OTT.S295542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039198PMC
April 2021

Case Report: Coinheritance of Germline Mutations in and in Colorectal Cancer.

Front Oncol 2021 25;11:658389. Epub 2021 Mar 25.

Department of Oncology, Nanjing Tongren Hospital, Nanjing, China.

Deleterious mutations in gene cause the autosomal dominant familial adenomatous polyposis (FAP) which is typically characterized by the occurrence of hundreds to thousands of colorectal adenomas that eventually lead to colorectal cancers (CRCs). are the two major susceptibility genes for breast and ovarian cancers. Here, we reported a coinheritance of mutations in and genes in a 20-year-old CRC patient with typical clinical features for FAP. Multiple relatives in the family of the patient were affected by colorectal and other cancers. Next-generation sequencing analysis using a panel consisting of 53 hereditary cancer related genes revealed a maternally inherited (exon15cn_del) mutation and a paternally inherited (p.lle1824AspfsX3) mutation. This is the first coexistence of and mutations in a CRC patient with the mutation inheritance pattern comprehensively characterized in the family. The patient underwent a colonoscopy and a subtotal colectomy and was subsequently diagnosed with colonic adenocarcinomas accompanied with hundreds of tubulovillous adenomas. The case reveals the scenario where two disease-causing mutations of different hereditary tumor syndromes coexist, and illustrates the importance of evaluating detailed family history and performing a multiple-gene panel test in patients with hereditary cancer.
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http://dx.doi.org/10.3389/fonc.2021.658389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030582PMC
March 2021

Maternal exposure to ambient air pollution and congenital heart defects in China.

Environ Int 2021 Aug 7;153:106548. Epub 2021 Apr 7.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China.

Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes.

Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m] increase in PM was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed.

Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.
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http://dx.doi.org/10.1016/j.envint.2021.106548DOI Listing
August 2021

Increased risk of multiple pregnancy complications following large-scale power outages during Hurricane Sandy in New York State.

Sci Total Environ 2021 May 24;770:145359. Epub 2021 Jan 24.

Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Albany, NY 12144, USA. Electronic address:

Background: Large-scale power outages (PO) are increasing in the context of climate change. Although some research has been conducted into the adverse health impacts of POs, significant gaps remain regarding whether POs would affect the health of pregnant women. We investigated the association between ED visits due to pregnancy complications and the occurence, intensity, and duration of large-scale POs in eight Sandy-affected counties in New York State (NYS).

Methods: In this cross-sectional study, daily ED visits for pregnancy complications and large-scale PO data in eight counties in NYS from October to December in 2005-2014 were collected. Using time-series analysis, we estimated the relative increase in ED visits for pregnancy complications during POs compared with non-PO periods at lag 0-7 days. Short-term health impacts of PO intensity and PO duration were investigated. Estimations were also stratified by sociodemographic characteristics and disease subtypes including threatened or spontaneous abortion, threatened or early labor, hypertension complications, infections of genitourinary tract, renal diseases, gestational diabetes mellitus, mental illnesses, and cardiovascular diseases during pregnancy.

Results: From October to December in 2005-2014, there were 307,739 ED visits for pregnancy complications in the eight counties. We found significant increases in ED visits for overall pregnancy complications (16.6%, 95% confidence interval [CI]: 10.3%, 23.2%) during the Hurricane-PO period at lag 0-7 days. The ED visits increased by 8.8% per level increase in PO intensity and 1.4% per day increase in PO duration. Specifically, threatened/early delivery and gestational diabetes mellitus during the PO period increased by 26.7% (95% CI: 8.2%, 48.4%) and 111.8% (95% CI: 16.7%, 284.4%), respectively. Young adult, Black, Hispanic, and uninsured individuals were at higher risk of complications.

Conclusions: POs may adversely impact pregnancy, especially for certain pregnancy complications and among low sociodemographic women.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145359DOI Listing
May 2021

Application of data science methods to identify school and home risk factors for asthma and allergy-related symptoms among children in New York.

Sci Total Environ 2021 May 23;770:144746. Epub 2021 Jan 23.

Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY 12144, USA. Electronic address:

Objectives: Few studies have comprehensively assessed multiple environmental exposures affecting children's health. This study applied machine-learning methods to evaluate how indoor environmental conditions at home and school contribute to asthma and allergy-related symptoms.

Methods: We randomly selected 10 public schools representing different socioeconomic statuses in New York State (2017-2019) and distributed questionnaires to students to collect health status and home-and school-environmental exposures. Indoor air quality was measured at school, and ambient particle exposures (PM and components) were measured using real-time personal monitors for 48 h. We used random forest model to identify the most important risk factors for asthma and allergy-related symptoms, and decision tree for visualizing the inter-relationships among the multiple risk factors with the health outcomes.

Results: The top contributing factors identified for asthma were family rhinitis history (relative importance: 10.40%), plant pollen trigger (5.48%); bedroom carpet (3.58%); environmental tobacco smoke (ETS) trigger symptom (2.98%); and ETS exposure (2.56%). For allergy-related symptoms, plant pollen trigger (10.88%), higher paternal education (7.33%), bedroom carpet (5.28%), family rhinitis history (4.78%), and higher maternal education (4.25%) were the strongest contributing factors. Conversely, primary heating with hot water radiator was negatively (-6.86%) associated with asthma symptoms. Younger children (<9 years old) with family history of rhinitis and carpeting in the bedroom were the prominent combined risk factors for asthma. Children jointly exposed to pollen, solvents, and carpeting in their home tended to have greater risks of allergy-related symptoms, even without family history of rhinitis.

Conclusion: Family rhinitis history, bedroom carpet, and pollen triggers were the most important risk factors for both asthma and allergy-related symptoms. Our new findings included that hot-water radiator was related to reduced asthma symptoms, and the combination of young age, rhinitis history, and bedroom carpeting was related to increased asthma symptoms. Further studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144746DOI Listing
May 2021

Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series.

Diagn Pathol 2021 Mar 11;16(1):21. Epub 2021 Mar 11.

Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

Background: In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.

Case Presentation: Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.

Conclusion: Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.
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http://dx.doi.org/10.1186/s13000-021-01083-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953741PMC
March 2021

Ambient extreme heat exposure in summer and transitional months and emergency department visits and hospital admissions due to pregnancy complications.

Sci Total Environ 2021 Jul 1;777:146134. Epub 2021 Mar 1.

Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, One University Place, Rensselaer, Albany, NY 12144, USA. Electronic address:

Although extreme heat exposure (EHE) was reported to be associated with increased risks of multiple diseases, little is known about the effects of EHE on pregnancy complications. We examined the EHE-pregnancy complications associations by lag days, subtypes, sociodemographic characteristics, and areas in New York State (NYS). We conducted a case-crossover analysis to assess the EHE-pregnancy complications associations in summer (June-August) and transitional months (May and September). All emergency department (ED) visits and hospital admissions due to pregnancy complications (ICD 9 codes: 630-649) from 2005 to 2013 in NYS were included. Daily mean temperature > 90th percentile of the monthly mean temperature in each county was defined as an EHE. We used conditional logistic regression while controlling for other weather factors, air pollutants and holidays to assess the EHE-pregnancy complications associations. EHE was significantly associated with increased ED visits for pregnancy complications in summer (ORs ranged: 1.01-1.04 from lag days 0-5). There was also a significant and stronger association in transitional months (ORs ranged: 1.02-1.06, Lag 0). Furthermore, we found EHE affected multiple subtypes of pregnancy complications, including threatened/spontaneous abortion, renal diseases, infectious diseases, diabetes, and hypertension (ORs range: 1.13-1.90) during transitional months. A significant concentration response effect between the number of consecutive days of EHE and ED visits in summer (P for trend <0.001), ED visits in September (P for trend =0.03), and hospital admission in May (P for trend<0.001) due to pregnancy complications was observed, respectively. African Americans and residents in lower socioeconomic position (SEP) counties were more susceptible to the effects of EHE. In conclusion, we found an immediate and prolonged effect of EHE on pregnancy complications in summer and a stronger, immediate effect in transitional months. These effects were stronger in African Americans and counties with lower SEP. Earlier warnings regarding extreme heat are recommended to decrease pregnancy complications.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146134DOI Listing
July 2021

The immediate effects of winter storms and power outages on multiple health outcomes and the time windows of vulnerability.

Environ Res 2021 05 6;196:110924. Epub 2021 Mar 6.

Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY, USA.

Background: While most prior research has focused on extreme heat, few assessed the immediate health effects of winter storms and associated power outages (PO), although severe storms have become more frequent. This study evaluates the joint and independent health effects of winter storms and PO, snow versus ice-storm, effects by time window (peak timing, winter/transitional months) and the impacts on critical care indicators including numbers of comorbidity, procedure, length of stay and cost.

Methods: We use distributed lag nonlinear models to assess the impacts of winter storm/PO on hospitalizations due to cardiovascular, lower respiratory diseases (LRD), respiratory infections, food/water-borne diseases (FWBD) and injuries in New York State on 0-6 lag days following storm/PO compared with non-storm/non-PO periods (references), while controlling for time-varying factors and PM. The storm-related hospitalizations are described by time window. We also calculate changes in critical care indicators between the storm/PO and control periods.

Results: We found the joint effects of storm/PO are the strongest (risk ratios (RR) range: 1.01-1.90), followed by that of storm alone (1.02-1.39), but not during PO alone. Ice storms have stronger impacts (RRs: 1.04-3.15) than snowstorms (RRs: 1.03-2.21). The storm/PO-health associations, which occur immediately, and some last a whole week, are stronger in FWBD, October/November, and peak between 3:00-8:00 p.m. Comorbidity and medical costs significantly increase after storm/PO.

Conclusion: Winter storms increase multiple diseases, comorbidity and medical costs, especially when accompanied by PO or ice storms. Early warnings and prevention may be critical in the transitional months and afternoon rush hours.
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http://dx.doi.org/10.1016/j.envres.2021.110924DOI Listing
May 2021

High-Intensity Focused Ultrasound Combined With Gonadotropin-Releasing Hormone Agonist or Levonorgestrel-Releasing Intrauterine System in Treating Dysmenorrhea of Severe Adenomyosis.

J Comput Assist Tomogr 2021 Mar-Apr 01;45(2):224-231

From the Department of Gynaecology, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin.

Objective: The objective of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist or levonorgestrel-releasing intrauterine system (LNG-IUS) in treating dysmenorrhea in patients with severe adenomyosis.

Methods: A retrospective analysis was performed on 243 patients diagnosed with severe adenomyosis. Patients were divided into H (received HIFU alone), H-G (received HIFU combined with gonadotropin-releasing hormone agonist), and H-L (received HIFU combined with LNG-IUS) groups. Their clinical results were compared at 3 months, 6 months, and 12 months after treatment.

Results: The effective rates of dysmenorrhea relief in the 3 groups after 3 months were 95.24% in the H group, 98.8% in the H-G group, and 94.74% in the H-L group; those after 6 months were 88.10% in the H group, 95.18% in the H-G group, and 84.21% in the H-L group; those after 12 months were 77.38% in the H group, 79.52% in the H-G group, and 96.05% in the H-L group. There was significant difference in effective rates of dysmenorrhea relief among 3 groups after 12 months of treatment, but not 3 or 6 months. In addition, at 12 months after treatment, there were significant differences in the efficacy of dysmenorrhea between patients of different ages or different ablation rates in group H. However, there was no significant difference in the H-G group and the H-L group.

Conclusions: High-intensity focused ultrasound alone is effective in alleviating the symptoms of dysmenorrhea in short term. However, HIFU combined with LNG-IUS improves the therapeutic effect for a longer period.
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http://dx.doi.org/10.1097/RCT.0000000000001138DOI Listing
April 2021

Structural and developmental principles of neuropil assembly in C. elegans.

Nature 2021 03 24;591(7848):99-104. Epub 2021 Feb 24.

Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.

Neuropil is a fundamental form of tissue organization within the brain, in which densely packed neurons synaptically interconnect into precise circuit architecture. However, the structural and developmental principles that govern this nanoscale precision remain largely unknown. Here we use an iterative data coarse-graining algorithm termed 'diffusion condensation' to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy coupled with lineage-tracing and cell-tracking algorithms to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth-based on pioneer neurons-that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain.
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http://dx.doi.org/10.1038/s41586-020-03169-5DOI Listing
March 2021

Parental variation in CHG methylation is associated with allelic-specific expression in elite hybrid rice.

Plant Physiol 2021 Feb 23. Epub 2021 Feb 23.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, 430070 Wuhan, China.

Heterosis refers to the superior performance of hybrid lines over inbred parental lines. Besides genetic variation, epigenetic differences between parental lines are suggested to contribute to heterosis. However, the precise nature and extent of differences between the parental epigenomes and the reprograming in hybrids that governs heterotic gene expression remain unclear. In this work, we analyzed DNA methylomes and transcriptomes of the widely cultivated and genetically studied elite hybrid rice (Oryza sativa) SY63, the reciprocal hybrid, and the parental varieties ZS97 and MH63, for which high-quality reference genomic sequences are available. We showed that the parental varieties displayed substantial variation in genic methylation at CG and CHG (H = A, C, or T) sequences. Compared with their parents, the hybrids displayed dynamic methylation variation during development. However, many parental differentially methylated regions (DMR) at CG and CHG sites were maintained in the hybrid. Only a small fraction of the DMRs displayed non-additive DNA methylation variation which, however, showed no overall correlation relationship with gene expression variation. By contrast, most of the allelic-specific expression (ASE) genes in the hybrid were associated with DNA methylation, and the ASE negatively associated with allelic-specific methylation (ASM) at CHG. These results revealed a specific DNA methylation reprogramming pattern in the hybrid rice and pointed to a role for parental CHG methylation divergence in ASE, which is associated with phenotype variation and hybrid vigor in several plant species.
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http://dx.doi.org/10.1093/plphys/kiab088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195538PMC
February 2021

Distinctive genomic characteristics in -mutant cancers can potentially predict beneficial clinical outcomes in patients who receive immune checkpoint inhibitor.

Ann Transl Med 2021 Jan;9(2):129

Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Mutations in proofreading domain can cause deficiencies in DNA repair, conferring ultramutated cancer phenotypes. Preliminary clinical studies have revealed an association between mutations and beneficial clinical outcomes to immune checkpoint inhibitor (ICI) therapy This study aims to investigate the genomic characteristics of mutant tumors and the prognostic value of mutation for ICI treatment.

Methods: Genomic data of 21,074 patients with 23 cancer types were retrieved from Burning Rock variant database (BR VarDB). The prevalence and spectra of and mutations were assessed and compared with that in The Cancer Genome Atlas (TCGA) samples. The correlations of mutation with tumor mutational burden (TMB) and microsatellite instability (MSI) were investigated. The prognostic value of mutations was also explored in 2,487 ICI-treated patients from published studies.

Results: BR VarDB samples displayed a similar mutational prevalence of (3.2% 3.2%) and (1.4% 1.6%, P=0.248) versusTCGA samples, but a slightly lower frequency of and co-mutations (0.21% 0.43%, P<0.001). -mutant tumors harbored increased TCT→TAT and TCG→TTG transversions, and genomic signatures associated with DNA mismatch repair (MMR) deficiency and ultra-hypermuation. Furthermore, tumors with proofreading mutation showed a significantly higher TMB than tumors with non-proofreading mutations (P<0.01), although both possessed a higher TMB than wild-type (WT) tumors (P<0.0001 and P<0.0001, respectively). MSI was commonly observed in tumors harboring dominant clone of mutation (10.2%), but occurred rarely in WT tumors (0.5%) and tumors with accumulating sub-cloned mutation (0%). Survival analysis revealed that mutation was not independently correlated with longer survival after adjusting for TMB and other factors (HR =0.86, P=0.372). However, patients harboring mutation demonstrated a higher response rate than patients with WT tumors (35.2% 19.6%, P=0.0165).

Conclusions: We delineated distinctive genomic characteristics in -mutant tumors, suggesting the potential predictive role of mutations, especially those in the proofreading domain, for beneficial outcomes of immunotherapy. Our results also suggest that MSI caused by a loss-of-function mutation in the MMR pathway tends to result from proofreading deficiency in mutant tumors with MSI.
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http://dx.doi.org/10.21037/atm-20-7553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867935PMC
January 2021

Temperature variation and preterm birth among live singleton deliveries in Shenzhen, China: A time-to-event analysis.

Environ Res 2021 04 3;195:110834. Epub 2021 Feb 3.

Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, No.74 Zhongshan Road #2, Guangzhou, 510080, China; Shanghai Key Laboratory of Meteorology and Health, Shanghai Meteorological Service, Shanghai, 200030, China; School of Public Health, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

Objective: Ambient temperature extremes due to heat exposure was an established risk factor for preterm birth (<37 gestational weeks). However, there is insufficient epidemiological evidence on the effects of temperature variation(TV), although TV is also associated with heat exposure and can influence human health risk. This study aimed to investigate the relationship between inter- and intraday TV and preterm birth (PTB).

Method: A total of 1,388,994 live singleton births were collected from January 2003 to December 2012, from the Shenzhen Birth registry system. Daily temperature range (DTR) was defined as the difference between the highest and lowest recorded daily temperature. Intraday TV was defined as the maximum daily diurnal temperature range in a given week (Max-DTR). Inter-day TV was defined as the maximum increase or decrease in daily mean temperature between days t and t-1in a given week; either an increase (Temp-inc) or a decrease (Temp-dec). We used Cox proportional hazards models to estimate TV-related PTB risks during the first trimester, the second trimester, and in late pregnancy.

Results: The maximum values for DTR, Temp-inc, and Temp-dec were 17 °C, 8 °C and 11 °C, respectively. The greatest TV-related PTB risk occurred in the second trimester, with 5.8% (95%CI: 3.3%, 8.3%), 23.7% (95%CI: 19.6%, 27.9%), and 4.4% (95%CI: 1.8%, 7.1%) differences per 1 °C increase in Max-DTR, Temp-inc, and Temp-dec, respectively. Greater TV was associated with elevated PTB risk during the warm season. The association between TV and PTB was modified by seasons, maternal education and chronic conditions.

Conclusions: Sharp TV is a likely risk factor for PTB. Policy makers and clinicians should recognize the potential role of TV in the etiology of PTB so that interventions can be designed to protect pregnant women and their fetuses against extreme temperatures.
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http://dx.doi.org/10.1016/j.envres.2021.110834DOI Listing
April 2021

Analysis of Rice Transcriptome Reveals the LncRNA/CircRNA Regulation in Tissue Development.

Rice (N Y) 2021 Jan 28;14(1):14. Epub 2021 Jan 28.

National Key Laboratory of Crop Genetic Improvement, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Background: Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can play important roles in many biological processes. However, no study of the influence of epigenetics factors or the 3D structure of the genome in their regulation is available in plants.

Results: In the current analysis, we identified a total of 15,122 lncRNAs and 7902 circRNAs in three tissues (root, leaf and panicle) in the rice varieties Minghui 63, Zhenshan 97 and their hybrid Shanyou 63. More than 73% of these lncRNAs and parental genes of circRNAs (P-circRNAs) are shared among Oryza sativa with high expression specificity. We found that, compared with protein-coding genes, the loci of these lncRNAs have higher methylation levels and the loci of circRNAs tend to locate in the middle of genes with high CG and CHG methylation. Meanwhile, the activated lncRNAs and P-circRNAs are mainly transcribed from demethylated regions containing CHH methylation. In addition, ~ 53% lncRNAs and ~ 15% P-circRNAs are associated with transposable elements (TEs), especially miniature inverted-repeat transposable elements and RC/Helitron. We didn't find correlation between the expression of lncRNAs and histone modifications; however, we found that the binding strength and interaction of RNAPII significantly affects lncRNA expression. Interestingly, P-circRNAs tend to combine active histone modifications. Finally, we found that lncRNAs and circRNAs acting as competing-endogenous RNAs have the potential to regulate the expression of genes, such as osa-156 l-5p (related to yield) and osa-miR444a-3p (related to N/P metabolism) confirmed through dual-luciferase reporter assays, with important roles in the growth and development of rice, laying a foundation for future rice breeding analyses.

Conclusions: In conclusion, our study comprehensively analyzed the important regulatory roles of lncRNA/circRNA in the tissue development of Indica rice from multiple perspectives.
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http://dx.doi.org/10.1186/s12284-021-00455-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843763PMC
January 2021

Silencing of circIgf1r plays a protective role in neuronal injury via regulating astrocyte polarization during epilepsy.

FASEB J 2021 Feb;35(2):e21330

Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy.
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http://dx.doi.org/10.1096/fj.202001737RRDOI Listing
February 2021

Carbon Fiber Reinforced Epoxy Vitrimer: Robust Mechanical Performance and Facile Hydrothermal Decomposition in Pure Water.

Macromol Rapid Commun 2021 Feb 23;42(3):e2000458. Epub 2020 Nov 23.

School of Mechanical and Materials Engineering, Composite Materials and Engineering Center, Washington State University, Pullman, WA, 99164, USA.

Conventional carbon fiber reinforced thermosetting polymers (CFRPs) are neither recyclable nor repairable due to their crosslinked network. The rapid growing CFRP market raises a serious concern of the waste management. In this work, a viable method to develop a readily recyclable CFRP based on epoxy vitrimer is introduced. First, a self-catalytic epoxy prepolymer with built-in hydroxy and tertiary amine groups is designed, which upon reaction with an anhydride formed a catalyst-free epoxy vitrimer. The epoxy prepolymer is synthesized from a diamine and an excess of bisphenol A epoxy resin. The hydroxyls and tertiary amines of the epoxy prepolymer efficiently catalyze both curing and the dynamic transesterification of the crosslinked polymer without the need of a catalyst. Then, the epoxy vitrimer is used as the matrix resin to prepare CFRP. The resulting CFRP exhibited a tensile strength as high as 356 MPa. More interestingly, the matrix of the CFRP is efficiently degraded in pure water at above 160 °C. This is because the built-in tertiary amines catalyze the hydrolysis of the ester bonds of the crosslinked network. The simple method developed in this work provides a framework for the development of recyclable CFRP.
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http://dx.doi.org/10.1002/marc.202000458DOI Listing
February 2021

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Prev Med 2021 02 7;143:106319. Epub 2020 Nov 7.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.
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http://dx.doi.org/10.1016/j.ypmed.2020.106319DOI Listing
February 2021

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

J Am Coll Nutr 2020 Oct 13:1-8. Epub 2020 Oct 13.

Department of Hepatobiliary Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Background: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important.

Objective: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics.

Methods: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People's Hospital, China, 2/16/2020-3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated.

Results: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19 nmol/L) to protect against COVID-19 was identified.

Conclusion: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID-19 disease.
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http://dx.doi.org/10.1080/07315724.2020.1826005DOI Listing
October 2020

Neurodegenerative hospital admissions and long-term exposure to ambient fine particle air pollution.

Ann Epidemiol 2021 02 30;54:79-86.e4. Epub 2020 Sep 30.

Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY; Center for Air Resources Engineering and Science, Clarkson University, Potsdam, NY.

Purpose: Long-term exposure to ambient fine particle (PM) concentrations has been associated with an increased rate or risk of neurodegenerative conditions, but individual PM sources have not been previously examined in relation to neurodegenerative diseases.

Methods: Using the Statewide Planning and Research Cooperative System database, we studied 63,287 hospital admissions with a primary diagnosis of either Alzheimer's disease, dementia, or Parkinson's disease for New York State residents living within 15 miles from six PM monitoring sites. In addition to PM concentrations, we studied seven specific PM sources: secondary sulfate, secondary nitrate, biomass burning, diesel, spark-ignition emissions, pyrolyzed organic rich, and road dust. We estimated the rate of neurodegenerative hospital admissions associated with increased concentration of PM and individual PM sources average concentrations in the previous 0-29, 0-179, and 0-364 days.

Results: Increases in ambient PM concentrations were not consistently associated with increased hospital admissions rates. Increased source-specific PM2.5 concentrations were associated with both increased (e.g., secondary sulfates and diesel emissions) and decreased rates (e.g., secondary nitrate and spark-ignition vehicular emissions) of neurodegenerative admissions.

Conclusions: We did not observe clear associations between overall ambient PM concentrations or source-apportioned ambient PM contributions and rates of neurologic disease hospitalizations.
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http://dx.doi.org/10.1016/j.annepidem.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796937PMC
February 2021

An alkali-tolerant phospholipase D from Sphingobacterium thalpophilum 2015: Gene cloning, overproduction and characterization.

J Gen Appl Microbiol 2021 Apr 28;67(1):1-8. Epub 2020 Sep 28.

College of Life Science and Technology, Southwest Minzu University.

The phospholipase pl-S.t gene of Sphingobacterium thalpophilum 2015 was cloned and the gene sequence was submitted to NCBI with Accession Number KX674735.1. The phylogenetic analysis showed that this PL-S.t was clustered to phospholipase D (PLD). As far as we know, the PL-S.t with a molecular mass of 22.5 kDa is the lowest of the currently purified bacterial PLDs, which belongs to a non-HKD PLD enzyme. This PL-S.t was resistant to a wide range of alkali pHs (7.5-9.0) after 1 h incubation, retaining more than 90% of its maximum activity. The PL-S.t activity can be enhanced by Ni, Co and Mn. This PL-S.t has only one cysteine residue and fewer negatively-charged amino acids (AAs). The hydrogen bonds network was found around the cystein108, which may be beneficial to the stability and activity of PL-S.t in Ni solution. This study has laid the foundation for further research on the molecular mechanism of the catalytic characteristics of low molecular weight alkalic PLD from S. thalpophilum 2015.
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http://dx.doi.org/10.2323/jgam.2020.01.012DOI Listing
April 2021

Association Between Residential Greenness, Cardiometabolic Disorders, and Cardiovascular Disease Among Adults in China.

JAMA Netw Open 2020 09 1;3(9):e2017507. Epub 2020 Sep 1.

Guangdong Provincial Engineering Technology Research Center of Environmental and Health Risk Assessment, Department of Occupational and Environmental Health, Sun Yat-sen University School of Public Health, Guangzhou, China.

Importance: Living in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD.

Objective: To evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China.

Design, Setting, And Participants: This analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km2) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020.

Main Outcomes And Measures: Lifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level.

Results: Among 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12 661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels.

Conclusions And Relevance: In this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.17507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506516PMC
September 2020

Is PM similar to PM? A new insight into the association of PM and PM with children's lung function.

Environ Int 2020 12 8;145:106092. Epub 2020 Sep 8.

Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Experimental data suggests that PM is more toxic than PM although the epidemiologic evidence suggests that the health associations are similar. However, few objective exposure data are available to compare the associations of PM and PM with children lung function. Our objectives are a) to evaluate associations between long-term exposure to PM, PM and children's lung function, and b) to compare the associations between PM and PM. From 2012 to 2013, we enrolled 6,740 children (7-14 years), randomly recruited from primary and middle schools located in seven cities in northeast China. We measured lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) utilizing two portable electronic spirometers. We dichotomized continuous lung function measures according the expected values for gender and age. The spatial resolution at which PM and PM estimated were estimated using a machine learning method and the temporal average concentrations were averaged from 2009 to 2012. A multilevel regression model was used to estimate the associations of PM, PM exposure and lung function measures, adjusted for confounding factors. Associations with lower lung function were consistently larger for PM than for PM. Adjusted odds ratios (OR) per interquartile range greater PM ranged from 1.53 for MMEF (95% confidence interval [CI]: 1.20-1.96) to 2.14 for FEV1 (95% CI: 1.66-2.76) and ORs for PM ranged from 1.36 for MMEF (95%CI: 1.12-1.66) to 1.82 for FEV1 (95%CI: 1.49-2.22), respectively. PM and PM had significant associations with FVC and FEV1 in primary school children, and on PEF and MMEF in middle school children. Long-term PM and PM exposure can lead to decreased lung function in children, and the associations of PM are stronger than PM. Therefore, PM may be more hazardous to children's respiratory health than PM exposure.
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http://dx.doi.org/10.1016/j.envint.2020.106092DOI Listing
December 2020

Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against .

Science 2020 07;369(6502):450-455

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.

The guanosine triphosphatase (GTPase) Rab32 coordinates a cell-intrinsic host defense mechanism that restricts the replication of intravacuolar pathogens such as Here, we show that this mechanism requires aconitate decarboxylase 1 (IRG1), which synthesizes itaconate, a metabolite with antimicrobial activity. We find that Rab32 interacts with IRG1 on infection and facilitates the delivery of itaconate to the -containing vacuole. Mice defective in IRG1 rescued the virulence defect of a serovar Typhimurium mutant specifically defective in its ability to counter the Rab32 defense mechanism. These studies provide a link between a metabolite produced in the mitochondria after stimulation of innate immune receptors and a cell-autonomous defense mechanism that restricts the replication of an intracellular bacterial pathogen.
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http://dx.doi.org/10.1126/science.aaz1333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020367PMC
July 2020

Evaluation of interactive effects between paternal alcohol consumption and paternal socioeconomic status and environmental exposures on congenital heart defects.

Birth Defects Res 2020 10 21;112(16):1273-1286. Epub 2020 Jul 21.

Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Background: While the maternal risk factors on congenital heart defects (CHDs) have often been assessed, paternal contribution to CHDs, especially the joint effects of paternal risk factors on CHDs remain unknown. This study examined the major impacts of paternal alcohol consumption and its interaction (on multiplicative and additive scales) with paternal socioeconomic status (SES) and environmental exposures on CHDs in China.

Methods: A population-based case-control study involving 4,726 singleton CHDs cases and 4,726 controls (without any malformation and matched on hospital, gender, and gestational age) was conducted in Guangdong, China, 2004-2014. Information on parental demographics, behavioral patterns, disease/medication, and environmental exposures (3 months before pregnancy) was collected through face-to-face interviews. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for all parental factors.

Results: Paternal alcohol consumption was associated with an increased OR of CHDs (adjusted OR = 2.87, 95% CI: 2.25-3.65). Additionally, paternal smoking, industry occupation, organic solvent contact, virus infection and antibiotic use, living in rural areas, low household income, and migrant status were significantly associated with CHDs (ORs ranged: 1.42-4.44). Significant additive or multiplicative interactions were observed between paternal alcohol consumption and paternal smoking, industrial occupation, and low income on any CHDs (interaction contrast ratio [ICR] = 4.72, 95% CI: 0.96-8.47] and septal defects (ICRs ranged from 2.04 to 2.79, p < .05).

Conclusions: Paternal alcohol consumption and multiple paternal factors were significantly associated with CHDs in China. Paternal smoking and low SES factors modified paternal alcohol consumption-CHDs relationships. Further studies are needed to confirm these findings.
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http://dx.doi.org/10.1002/bdr2.1759DOI Listing
October 2020