Prenatal exposure to PM2.5 components and the risk of different types of preterm birth and the mediating effect of pregnancy complications: a cohort study.

OBJECTIVES: This study aims to reveal the single and mixed associations of PM2.5 and its components with very, moderately, and late preterm births and to explore the potential mediating role of pregnancy complications in PM2.5-induced preterm birth. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 168,852 mothers and matched the concentrations of PM2.5 and its five components (OM, SO42-, BC, NO3-, and NH4+) based on their geographical location. Next, we used generalized linear models, quantile g-computation, and mediation analysis to evaluate the associations of PM2.5 and its components with very, moderately, and late preterm births and the mediating role of pregnancy complications. RESULTS: Prenatal exposure to PM2.5 and its components was associated with preterm birth, and the association was strongest in the third trimester. Preterm birth was associated with co-exposure to a mixture of PM2.5 components in the third trimester, and the contributions of NO3-, NH4+, and BC to the risk of preterm birth were positive. Meanwhile, pregnancy complications mediated PM2.5-induced preterm birth. Moreover, very and moderately preterm births were associated with PM2.5 and its components in the second and third trimesters, and very and late preterm births were associated with co-exposure to a mixture of PM2.5 components in the third trimester. CONCLUSIONS: Later exposure to PM2.5 during pregnancy will cause earlier preterm birth. Targeted and positive interventions for anthropogenic sources of specific PM2.5 components and pregnancy complications are helpful for preterm birth prevention.

Risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta in China: A cross-sectional study.

PURPOSE: To describe the level of risk perception for fractures among family caregivers of children diagnosed with osteogenesis imperfecta, and explore the related factors. DESIGN AND METHODS: This was a cross-sectional survey study. A self-administered questionnaire on family caregivers' perception of fracture risk of underage patients with osteogenesis imperfecta was used. The study was performed in mainland China from May to December 2022, with 127 family caregivers of patients aged 3-17. Stepwise backwards multivariable linear regression analysis was undertaken to examine risk factors for caregivers' risk perception of fractures. RESULTS: A total of 16.54% of caregivers had a higher level of risk perception for fractures of patients. The caregiver's educational level, the family members, the patient's self-care ability, fracture times in the past year, and whether or not they had received community services were associated with the caregiver's risk perception for fracture. CONCLUSIONS: Patients with osteogenesis imperfecta will eventually leave the medical system and receive more support from themselves or family caregivers instead of health personnel. These findings should be incorporated into the prevention and health education of fractures in caregivers of underage patients with osteogenesis imperfecta to help develop effective risk communication strategies and induce caregivers to implement appropriate protective behaviors. PRACTICE IMPLICATIONS: It is important to evaluate the risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta. Identifying these factors can help healthcare providers to screen caregivers with high perceived level of fracture risk in a quicker and earlier way. This study provides evidence for the establishment of interventions to balance caregivers' risk perception and patient socialization.

[Bayesian network prediction study on the impact of occupational health psychological factors on insomnia among thermal power generation workers].

Objective: To explore the risk factors of insomnia among employees in the thermal power generation industry and the network relationships between their interactions, and to provide scientific basis for personalized interventions for high-risk groups with insomnia. Methods: In November 2022, 860 employees of a typical thermal power generation enterprise were selected as the research subjects by cluster sampling. On-site occupational health field surveys and questionnaire surveys were used to collect basic information, occupational characteristics, anxiety, depression, stress, occupational stress, and insomnia. The interaction between insomnia and occupational health psychological factors was evaluated by using structural equation model analysis and Bayesian network construction. Results: The detection rates of anxiety, depression and stress were 34.0% (292/860), 32.1% (276/860) and 18.0% (155/860), respectively. The total score of occupational stress was (445.3±49.9) points, and 160 workers (18.6%) were suspected of insomnia, and 578 workers (67.2%) had insomnia. Structural equation model analysis showed that occupational stress had a significant effect on the occurrence of insomnia in thermal power generation workers (standardized load coefficient was 0.644), and occupational health psychology had a low effect on insomnia (standardized load coefficient was 0.065). However, the Bayesian network model further analysis found that anxiety and stress were the two parent nodes of insomnia, with direct causal relationships, the arc strength was-8.607 and -15.665, respectively. The model prediction results showed that the probability of insomnia occurring was predicted to be 0 in the cases of no stress and anxiety, low stress without anxiety, and no stress with low anxiety. When high stress with low anxiety and low stress with high anxiety occurred, the predicted probability of insomnia occurring were 0.38 and 0.47, respectively. When both high stress and high anxiety occurred simultaneously, the predicted probability of insomnia occurring was 0.51. Conclusion: Bayesian network risk assessment can intuitively reveal and predict the insomnia risk of thermal power generation workers and the network interaction relationship between the risks. Anxiety and stress are the direct causal risks of insomnia, and stress is the main risk of individual insomnia of thermal power generation workers. The occurrence of insomnia can be reduced based on scientific intervention of stress conditions.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[Clinical and endoscopic characteristics of adult celiac disease].

Objective: The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment. Methods: In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed. Results: A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant (P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD (P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions: Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

[Study of immunophenotypic characteristics, clinicopathological parameters and prognosis in gastric cancer microenvironment].

Objective: To explore the immunophenotypic characteristics of gastric cancer microenvironment and analyze its correlation with clinicopathological parameters and prognosis of patients. Methods: The expression levels of leukocyte differentiation antigen (CD) 8, CD4, T lymphocyte immunoglobulin mucoprotein 3 (TIM3), human forkhead box protein P3 (Foxp3) and co-localized tumor infiltrating lymphocytes (TILs) were detected in 92 cases of gastric cancer tissue [58 males and 34 females; aged M(Q1, Q3), 70(59, 77) years ] and 84 cases of paracancer tissue [57 males and 27 females, aged 70(59, 77) years] purchased from Shanghai Xinchao Biotechnology Co., Ltd., and the samples were from 28 hospitals in the sample bank. Gastric cancer and adjacent tissues were divided into high expression group and low expression group according to the optimal cut-off value of positive lymphocytepercentage. The expression of immunophenotypes in gastric cancer and adjacent tissues was analyzed. Kaplan-Meier method was used for survival analysis. Cox proportional hazard model was used to explore the prognostic factors of gastric cancer patients. Results: The optimal cut-off values of CD8, CD4, TIM3 and Foxp3 positive cells in gastric cancer were 12.73%, 1.39%, 10.77% and 2.44%, respectively. The expression of Foxp3 in gastric cancer tissues was higher than that in paracancer tissues [M (Q1, Q3), 0.93 (0.45, 2.16) vs 0.31 (0.09, 0.86), P<0.001], and the expression of CD8 [4.92 (2.34, 8.80) vs 8.81 (6.61, 12.17), P<0.001], CD4 [4.79 (1.77, 11.36) vs 8.40 (4.84, 12.77), P=0.022] and TIM3 [5.68 (2.05, 11.58) vs 7.07 (3.13, 11.43), P=0.338] were lower than that in paracancer tissues. There were significant differences in TIM3 expression in gastric cancer patients with different lymph node metastasis and clinical stage (all P<0.05). The 5-year survival rate of patients with high CD4 expression, low TIM3 expression and low Foxp3 expression in gastric cancer tissues was poor, among which the high CD4 expression and low CD4 expression groups were 29.3% and 64.7%, respectively; The high and low TIM3 expression groups were 60.9% and 30.4%, respectively; The high and low Foxp3 expression groups were 64.3% and 33.3%, respectively (all P<0.05). The optimal cut-off values of CD8+TIM3+TILs, CD4+TIM3+TILs, CD8+Foxp3+TILs and CD4+Foxp3+TILs were 3.86%, 0.23%, 0.08% and 0.76%, respectively. Colocalization analysis showed that the expression of CD8+Foxp3+TILs in gastric cancer tissues was higher than that in adjacent tissues(all P<0.05). Multivariate Cox regression analysis showed that high expression of CD4 (HR=3.079, 95%CI: 1.350-7.024,P=0.008), low expression of TIM3 (HR=0.428, 95%CI: 0.208-0.879, P=0.021) and low expression of Foxp3 (HR=0.288, 95%CI: 0.121-0.687, P=0.005) were the influencing factor for the 5-year survival rate of patients with gastric cancer after operation. Conclusions: Gastric cancer tissues have complex immune microenvironment characteristics. The expression of CD4, TIM3 and Foxp3 is closely related to the prognosis of patients.

Spin-Holstein Models in Trapped-Ion Systems.

In this work, we highlight how trapped-ion quantum systems can be used to study generalized Holstein models, and benchmark expensive numerical calculations. We study a particular spin-Holstein model that can be implemented with arrays of ions confined by individual microtraps, and that is closely related to the Holstein model of condensed matter physics, used to describe electron-phonon interactions. In contrast to earlier proposals, we focus on simulating many-electron systems and inspect the competition between charge-density wave order, fermion pairing, and phase separation. In our numerical study, we employ a combination of complementary approaches, based on non-Gaussian variational ansatz states and matrix product states, respectively. We demonstrate that this hybrid approach outperforms standard density-matrix renormalization group calculations.

Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). STUDY DESIGN: We undertook an ecological study using routinely available national data. METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

[Clinical characteristics and related factors of human respiratory syncytial viruses infection in premature infants within 2 years after birth in Shenzhen Children's Hospital].

Objective: To analyze the clinical characteristics and factors associated with human respiratory syncytial virus (HRSV) infection in preterm infants within the first 2 years of life. Methods: Children with respiratory tract infections admitted to Shenzhen Children's Hospital during the 3-year period from January 2016 to December 2018 who were <2 years old and whose gestational age at birth was <37 weeks were selected, and those who met the diagnostic criteria for RSV infection were categorized as the positive case group, and those who had no detectable influenza virus, parainfluenza virus and adenovirus antigens were categorized as the negative group. The clinical characteristics of the case group were retrospectively analyzed. A multivariable logistic regression model was used to analyze the associated factors. Results: A total of 1, 483 children were included, of whom 149 (10.1%) were HRSV positive (case group) and 447 (30.1%) were in the negative group (control group). In the case group, there were 88 (59.1%) male and 61 (40.1%) female children; 127 children (85.2%) in the mild-to-moderate disease group and 22 children (14.8%) in the severe disease group. The number of cases in the severe disease group was greater than that in the mild-to-moderate disease group [(17 cases, 77.3%) than (59 cases, 46.5%)], with statistical significance (P=0.010). A total of 117 cases (78.5%) had onset from February to July. Multivariable analysis showed that males [OR (95%CI) of 0.105 (0.013-0.112)], age at month [0.045 (0.036-0.112)], congenital heart disease [0.388 (0.206-0.940)] and bronchopulmonary dysplasia [0.622 (0.484-0.927)] were positively associated with HRSV infection in preterm infants. Conclusion: The high prevalence of HRSV infection in preterm infants in Shenzhen is from February to July each year, and male children are more common. Young age, congenital heart disease and bronchopulmonary dysplasia are all independent risk factors for HRSV infection in preterm infants.

Headaches Associated With Personal Protective Equipment - A Cross-Sectional Study Among Frontline Healthcare Workers During COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective equipment (PPE) such as N95 face mask and protective eyewear while attending to patients. OBJECTIVES: We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated. METHODS: This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire. RESULTS: A total of 158 healthcare workers participated in the study. Majority [126/158 (77.8%)] were aged 21-35 years. Participants included nurses [102/158 (64.6%)], doctors [51/158 (32.3%)], and paramedical staff [5/158 (3.2%)]. Pre-existing primary headache diagnosis was present in about a third [46/158 (29.1%)] of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards [7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001] or medical ICU [7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001]. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance. CONCLUSION: Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.

Can elevated concentrations of ALT and AST predict the risk of 'recurrence' of COVID-19?

'Recurrence' of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of 'recurrence' of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.

Long noncoding RNA UCA1 regulates CCR7 expression to promote tongue squamous cell carcinoma progression by sponging miR-138-5p.

Tongue squamous cell carcinoma (TSCC) is a malignant tumor. Long noncoding RNAs (lncRNAs) have been proved to be involved in the regulation of the progression of various cancers. However, the mechanism of lncRNA urothelial cancer-associated 1 (UCA1) in the progression of TSCC remains unclear. The expression levels of UCA1, microRNA-138-5p (miR-138-5p), and CC chemokine receptor 7 (CCR7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion were detected using colony formation assay and transwell assay, respectively. Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related proteins and CCR7 protein. Moreover, the extracellular acidification rate (ECAR) of cells was measured by the Seahorse XF Extracellular Flux Analyzer, and the adenosine triphosphate (ATP) level, glucose uptake, and lactate produce of cells were tested by their corresponding assay kits. Further, the dual-luciferase reporter assay was used to confirm the interaction between miR-138-5p and UCA1 or CCR7. In addition, the effect of UCA1 on TSCC tumor growth in vivo was evaluated by animal experiments. We found that UCA1 and CCR7 were upregulated, while miR-138-5p was downregulated in TSCC tissues. Silenced UCA1 restrained the proliferation, migration, invasion, and glycolysis metabolism of TSCC cells. Similarly, knockdown of CCR7 also could suppress the progression of TSCC. Besides, UCA1 overexpression promoted TSCC progression, while this promotion effect could be reversed by CCR7 silencing. miR-138-5p could be sponged by UCA1 and could target CCR7. Additionally, miR-138-5p overexpression could reverse the promotion effect of overexpressed UCA1 on TSCC progression. Furthermore, the UCA1 knockdown reduced TSCC tumor growth in vivo. In conclusion, lncRNA UCA1 might function as an oncogene in TSCC through regulating the miR-138-5p/CCR7 axis, providing a new biomarker for TSCC treatment.

Topological phenomena in classical optical networks.

We propose a scheme to realize a topological insulator with optical-passive elements and analyze the effects of Kerr nonlinearities in its topological behavior. In the linear regime, our design gives rise to an optical spectrum with topological features and where the bandwidths and bandgaps are dramatically broadened. The resulting edge modes cover a very wide frequency range. We relate this behavior to the fact that the effective Hamiltonian describing the system's amplitudes is long range. We also develop a method to analyze the scheme in the presence of a Kerr medium. We assess robustness and stability of the topological features and predict the presence of chiral squeezed fluctuations at the edges in some parameter regimes.

Methionine Limitation Impairs Pathogen Expansion and Biofilm Formation Capacity.

Multidrug-resistant bacterial pathogens are becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. Bacterial central metabolism is crucial for catabolic processes and provides precursors for anabolic pathways, such as the biosynthesis of essential biomolecules like amino acids or vitamins. However, most essential pathways are not regarded as good targets for antibiotic therapy since their products might be acquired from the environment. This issue raises doubts about the essentiality of such targets during infection. A putative target in bacterial anabolism is the methionine biosynthesis pathway. In contrast to humans, almost all bacteria carry methionine biosynthesis pathways which have often been suggested as putative targets for novel anti-infectives. While the growth of methionine auxotrophic strains can be stimulated by exogenous methionine, the extracellular concentrations required by most bacterial species are unknown. Furthermore, several phenotypic characteristics of methionine auxotrophs are only partly reversed by exogenous methionine. We investigated methionine auxotrophic mutants of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli (all differing in methionine biosynthesis enzymes) and found that each needed concentrations of exogenous methionine far exceeding that reported for human serum (∼30 µM). Accordingly, these methionine auxotrophs showed a reduced ability to proliferate in human serum. Additionally, S. aureus and P. aeruginosa methionine auxotrophs were significantly impaired in their ability to form and maintain biofilms. Altogether, our data show intrinsic defects of methionine auxotrophs. This result suggests that the pathway should be considered for further studies validating the therapeutic potential of inhibitors.IMPORTANCE New antibiotics that attack novel targets are needed to circumvent widespread resistance to conventional drugs. Bacterial anabolic pathways, such as the enzymes for biosynthesis of the essential amino acid methionine, have been proposed as potential targets. However, the eligibility of enzymes in these pathways as drug targets is unclear because metabolites might be acquired from the environment to overcome inhibition. We investigated the nutritional needs of methionine auxotrophs of the pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli We found that each auxotrophic strain retained a growth disadvantage at methionine concentrations mimicking those available in vivo and showed that biofilm biomass was strongly influenced by endogenous methionine biosynthesis. Our experiments suggest that inhibition of the methionine biosynthesis pathway has deleterious effects even in the presence of external methionine. Therefore, additional efforts to validate the effects of methionine biosynthesis inhibitors in vivo are warranted.

Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies.

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Alterations in the intestinal microbiota of patients with severe and active Graves' orbitopathy: a cross-sectional study.

BACKGROUND: The intestinal microbiota was linked to autoimmune diseases. Graves' orbitopathy (GO) is an autoimmune disease that is usually associated with Graves' disease. However, information on the microbiome of GO patients is yet lacking. OBJECTIVES: To investigate whether GO patients differ from healthy controls in the fecal microbiota. DESIGN: A cross-sectional study. SETTING: 33 patients with severe and active GO and 32 healthy controls of Han nationality were enrolled between March 2017 and March 2018. METHODS: The Gut microbial communities of the fecal samples of GO patients and healthy controls were analyzed and compared by 16S rRNA gene sequencing. RESULTS: Community diversity (Simpson and Shannon) was significantly reduced in fecal samples from patients with GO as compared to controls (p < 0.05). The similarity observed while assessing the community diversity (PCoA) proposed that the microbiota of patients with GO differ significantly from those of controls (p < 0.05). At the phyla levels, the proportion of Bacteroidetes increased significantly in patients with GO (p < 0.05), while at the genus and species levels, significant differences were observed in the bacterial profiles between the two groups (p < 0.05). LIMITATIONS: Single-centered study design and limited fecal samples. CONCLUSIONS: The present study indicated distinctive features of the gut microbiota in GO patients. The study provided evidence for further exploration in the field of intestinal microbiota with respect to the diagnosis and treatment of GO patients by modifying the microbiota profile.

A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy.

OBJECTIVE: Graves' orbitopathy (GO) is an inflammatory orbital disease of autoimmune origin with the potential to cause severe functional and psychosocial effects. The pathogenesis has not been fully elucidated. We investigated whether DNA methylation was associated with GO incidence in Chinese patients. MATERIALS AND METHODS: Six GO patients and six age-matched controls were recruited, and genome-wide DNA methylation patterns were analyzed in their peripheral blood. t tests were performed to determine differential methylated sites in genomic regions and the univariable logistic regression analyses was performed to evaluate their risk with GO incidence. Cluster analysis and principal component analysis (PCA) were performed to determine the effects of the extracted differentially methylated sites. RESULTS: One hundred and forty-eight differentially methylated sites were identified, including CD14 (fold change = 4.31, p = 0.005), IL17RE (fold change = 2.128, p = 0.005), and DRD4 (fold change = 0.25, p = 0.004), and were supported by cluster and PCA analyses. Univariable logistic regression analyses showed that the methylation patterns at 12 loci were associated with GO incidence. The relative risk per 1% decrease in methylation at ZCCHC6 and GLI3 was 0.15 (95% CI 0.03-0.91; p = 0.039) and 0.65 (95% CI 0.42-0.98; p = 0.042), respectively. Pearson correlation analyses demonstrated that methylation levels at IL17RE were positively associated with Clinical Activity Score (CAS) (r = 0.967, p < 0.05). CONCLUSIONS: Our results demonstrate that differential methylation levels at analyzed sites (genes) may be risk markers of GO. DNA methylation analysis could provide new insights into understanding the disease and provide new treatment strategies for GO in Chinese patients.

[Effects of Personality and Psychological Acceptance on Medical Workers' Occupational Stress].

Objective: To assess psychological acceptance and occupational stress of medical staff, analyze the relationship among personality, psychological acceptance and occupational stress and discuss the direct or indirect effects of personality to occupational stress. Methods: Eysenck Personality Questionnaire (EPQ-RSC) , Acceptance and Action Questionnaire-II (AAQ-Ⅱ) and Revised Occupational Stress Inventory (OSI-R) were administered to 749 medical staff. Results: The level of occupational stress of medical staff was high, the score of PSY was 26.8±7.13 and the score of PHS was 24.3±6.50. Personality and psychological acceptance can predict occupational stress. Psychological acceptance was a protective factor of occupational stress. Medical staff with personality of introversion, neuroticism and psychoticism suffered higher occupational stress. Personality have both direct and indirect effects on occupational stress. Neuroticism have the strongest effect on occupational stress with effect size of 0.496 (psychological stress) and 0.431 (physical strain) . Conclusion: Medical staff have heavier occupational stress. There is a significant correlation between personality and occupational stress. Measures depending on personality should be taken to deal with this situation.

[Clinical pathological characteristics of resectable papillary thyroid microcarcinoma].

Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm). Results: The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto's thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82). Conclusions: Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.