[Constructing an early-warning model for mortality risk in heat stroke patients based on Fisher discriminant analysis].

Objective: To establish an early warning model to assess the mortality risk of patients with heat stroke disease. Methods: The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model. Results: The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%. Conclusion: The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

CREB inactivation by HDAC1/PP1γ contributes to dopaminergic neurodegeneration in Parkinson's disease.

Understanding the pathogenesis of nigral dopaminergic neurodegeneration is critical for developing mechanism-based treatments for Parkinson's disease (PD). In the nigral dopaminergic neurons of postmortem human PD brains, we found that CREB, a well-recognized pro-survival transcription factor in neurons, was inactivated by dephosphorylation at Ser133. CREB dephosphorylation correlated with decreased expression of NURR1, one of its target genes crucial for dopaminergic neuron survival, confirming that CREB function was impaired in nigral dopaminergic neurons in PD. An MPTP mouse model was used to further elucidate the mechanism underlying CREB dephosphorylation. Protein phosphatase 1γ (PP1γ), which dephosphorylates CREB, was constitutively associated with histone deacetylase 1 (HDAC1). HDAC1 promotes CREB Ser133 dephosphorylation via a stable interaction with PP1γ. We found that CREB interacted with the HDAC1/PP1γ complex during dopaminergic neurodegeneration. Importantly, increased CREB/HDAC1 interaction occurred in the nigral dopaminergic neurons of PD patients as demonstrated using a proximity ligation assay. Disrupting CREB/HDAC1 interaction via either overexpression of GAL4 M1, a CREB mutant, or administration of trichostatin A, a pan-HDAC inhibitor, restored the expression levels of phospho-CREB (Ser133) and NURR1, and protected nigral dopaminergic neurons in the MPTP-treated mice brain. Collectively, our results demonstrated that HDAC1/PP1γ-mediated CREB inactivation contributed to dopaminergic neuronal degeneration. Disruption of CREB/HDAC1 interaction has the potential as a new approach for PD therapy.Significance StatementPD is the most common movement disorder attributed to the progressive loss of dopaminergic neurons in the substantia nigra. Understanding the pathogenesis of nigral dopaminergic neurodegeneration is critical for developing mechanism-based treatments for PD. We found in nigral dopaminergic neurons of postmortem human PD brains that CREB, a well-recognized pro-survival transcription factor in neurons, was inactivated by dephosphorylation at Ser133. HDAC1, constitutively associated with PP1γ, interacted with CREB to mediate its dephosphorylation during dopaminergic degeneration. Disrupting CREB/HDAC1 interaction restored CREB activity and protected nigral dopaminergic neurons in the MPTP mouse brains. This work suggests that disruption of the CREB/HDAC1 interaction to restore CREB activity may be a potential therapeutic approach in PD.

Prevalence trends of metabolic syndrome in residents of postdisaster Fukushima: a longitudinal analysis of Fukushima Health Database 2012-2019.

OBJECTIVES: The study aimed to evaluate the long-term metabolic risk profiles of Fukushima residents after the Great East Japan Earthquake of March 2011. STUDY DESIGN: This was a cross-sectional and a longitudinal design. METHODS: The Fukushima Health Database (FDB) contains 2,331,319 annual health checkup records of participants aged 40-74 years between 2012 and 2019. We checked the validity of the FDB by comparing the prevalence of metabolic factors with the National Database of Health Insurance Claims and Specific Health Checkups (NDB). We applied a regression analysis to determine the changes and project the trends of metabolic factors over the years. RESULTS: Compared to the NDB, the prevalence of metabolic factors in Fukushima was higher than the country average from 2013 to 2018, and they showed the same trends as those from the FDB. The prevalence of metabolic syndrome (MetS) increased from 18.9% in 2012 to 21.4% in 2019 (an annual increase of 2.74%) in men and from 6.8 to 7.4% (an annual increase of 1.80%) in women in Fukushima. The standardized prevalence of MetS, being overweight, and diabetes is projected to continue increasing, with disparities among subareas being higher in evacuees than in non-evacuees. An annual decrease of 0.38-1.97% in hypertension was mainly observed in women. CONCLUSIONS: The prevalence of metabolic risk is higher in Fukushima as compared to the country average. The increasing metabolic risk in subareas, including the evacuation zone, highlights the need to control MetS in Fukushima residents.

Lifestyle behaviour patterns in the prevention of type 2 diabetes mellitus: the Fukushima Health Database 2015-2020.

OBJECTIVES: Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. STUDY DESIGN: This is a cohort study. METHODS: In 2015, 193,246 participants aged 40-74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet-smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity-sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. RESULTS: The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet-smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity-sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity-sleep" pattern showed a significant inverse association in non-overweight men. CONCLUSIONS: Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults.

Knockout of the NONO Gene Inhibits Neointima Formation in a Mouse Model of Vascular Injury.

[Figure: see text].

Rapid antigen test during a COVID-19 outbreak in a private hospital in Hong Kong.

INTRODUCTION: In response to two nosocomial clusters of coronavirus disease 2019 (COVID-19) in our hospital, we adopted a series of strict infection control measures, including regular rapid antigen test (RAT) screening for high-risk patients, visitors, and healthcare workers. We evaluated the diagnostic performance of a locally developed RAT, the INDICAID COVID-19 Rapid Antigen Test (Phase Scientific, Hong Kong), using respiratory samples from both symptomatic and asymptomatic individuals. METHODS: Real-time reverse-transcription polymerase chain reaction (rRT-PCR)-confirmed deep throat saliva (DTS) and pooled nasopharyngeal swab and throat swab (NPS/TS) samples collected from 1 November to 30 November 2020 were tested by INDICAID. Screening RATs were performed on asymptomatic healthcare workers during a 16-week period (1 December 2020 to 22 March 2021). RESULTS: In total, 20 rRT-PCR-confirmed samples (16 DTS, four pooled NPS/TS) were available for RAT. Using the original sample, RAT results were positive in 17/20 samples, indicating 85% sensitivity (95% confidence interval [CI]=62.11%-96.79%). Negative RAT results were associated with higher cycle threshold (Ct) values. For samples with Ct values <25, the sensitivity was 100%. Of the 49 801 RATs collected from healthcare workers, 33 false positives and one rRT-PCR-confirmed case were detected. The overall specificity was 99.93% (95% CI=99.91%-99.95%). The positive and negative predictive values were 2.94% (95% CI=2.11%-4.09%) and 100%, respectively. CONCLUSION: The INDICAID COVID-19 RAT demonstrated good sensitivity for specimens with high viral loads and satisfactory specificity for low-risk, asymptomatic healthcare workers.

Nuclear receptor hormone receptor 39 is required for locust moulting by regulating the chitinase and carboxypeptidase genes.

The nuclear receptor-mediated 20-hydroxyecdysone (20E) signalling pathway plays crucial roles in insects by initiating and regulating moulting and metamorphosis. In the present study, we identified and characterized a cDNA encoding a putative nuclear receptor protein (Locusta migratoria hormone receptor 39, LmHR39) based on L. migratoria transcriptomics data. Reverse-transcription quantitative PCR (RT-qPCR) revealed that LmHR39 shows low-level expression in the early days of fifth-instar nymphs, and peak expression occurs on day 5, which is followed by a decrease before ecdysis. LmHR39 transcription could be induced by 20E in vivo and was significantly suppressed by knocking down the expression of the L. migratoria ecdysone receptor gene and early-late gene LmHR3. After RNA interference of LmHR39 with double-stranded RNA (dsRNA), 85% of the insects showed abnormal morphology, with curly wings after moulting and delayed eclosion time. Haematoxylin and eosin staining indicated that apolysis of the integument and wing pad cuticle in the dsLmHR39-treated insects was delayed compared to that in the dsRNA for green fluorescent protein-injected control. Furthermore, RNA-sequencing and RT-qPCR analysis showed the expression level of carboxypeptidase genes (Carboxypeptidase A (CPA) and Carboxypeptidase M (CPM)) and chitin degrading genes (LmChitinase5 (LmCHT5) and LmChitinase10 (LmCHT10)) dramatically declined in the dsLmHR39-treated insects, implying that the LmHR39-mediated 20E signalling pathway is involved in the regulation of carboxypeptidase genes (CPA and CPM) and chitinase genes (LmCHT5 and LmCHT10), and participated in apolysis of the integument and wing pads during locust moulting.

LmCDA1 organizes the cuticle by chitin deacetylation in Locusta migratoria.

Cells produce an extracellular matrix (ECM) with a stereotypic organization that is important for tissue function. The insect cuticle is a layered ECM that mainly consists of the polysaccharide chitin and associated proteins adopting a quasi-crystalline structure. Our understanding of the molecular mechanisms deployed during construction of the highly ordered protein-chitin ECM so far is limited. In this study, we report on the role of the chitin deacetylase 1 (LmCDA1) in the organization of the protein-chitin ECM in the migratory locust Locusta migratoria, and LmCDA1 localizes predominantly to the apical tier of the protein-chitin ECM, but it is also found in lower regions. Reduction of LmCDA1 function correlates with lower amounts of chitin and impedes conversion of chitin to chitosan by deacetylation. Establishment of the quasi-crystalline architecture of the protein-chitin ECM is, however, independent of LmCDA1 activity, but it is dependent on another chitin deacetylase, LmCDA2, which has no detectable effects on chitin deacetylation and, as shown previously, no influence on chitin content. Our data reveal that LmCDA1 and LmCDA2 act in parallel and independently from each other in defining the dimensions of the cuticle. Both enzymes are non-uniformly distributed within the protein-chitin matrix, suggesting a site-autonomous function.

Structural Parameter of Orientational Order to Predict the Boson Vibrational Anomaly in Glasses.

It has so far remained a major challenge to quantitatively predict the boson peak, a THz vibrational anomaly universal for glasses, from features in the amorphous structure. Using molecular dynamics simulations of a model Cu_{50}Zr_{50} glass, we decompose the boson peak to contributions from atoms residing in different types of Voronoi polyhedra. We then introduce a microscopic structural parameter to depict the "orientational order," using the vector pointing from the center atom to the farthest vertex of its Voronoi coordination polyhedron. This order parameter represents the most probable direction of transverse vibration at low frequencies. Its magnitude scales linearly with the boson peak intensity, and its spatial distribution accounts for the quasilocalized modes. This correlation is shown to be universal for different types of glasses.

Seatbelt use by pregnant women: a survey of knowledge and practice in Hong Kong.

INTRODUCTION: The use of motor vehicles is common during pregnancy. Correct seatbelt use during pregnancy has been shown to protect both the pregnant woman and her fetus. This survey aimed to evaluate the practices, beliefs, and knowledge of Hong Kong pregnant women of correct seatbelt use, and identify factors leading to reduced compliance and inadequate knowledge. METHODS: A self-administered survey was completed by postpartum women in the postnatal ward at the United Christian Hospital, Hong Kong, from January to April 2015. Eligible surveys were available from 495 women. The primary outcome was the proportion of pregnant women who maintained or reduced seatbelt use during pregnancy. Secondary outcomes were analysed and included knowledge of correct seatbelt use, as well as contributing factors to non-compliance and inadequate knowledge. RESULTS: There was decreased compliance with seatbelt use during pregnancy and the decrease was in line with increasing gestation. Pregnant women's knowledge about seatbelt use was inadequate and only a minority had received relevant information. Women who held a driving licence and had a higher education level were more likely to wear a seatbelt before and during pregnancy. Women with tertiary education or above knew more about seatbelt use. CONCLUSIONS: Public health education for pregnant women in Hong Kong about road safety is advisable, and targeting the lower-compliant groups may be more effective and successful.

Interaction of dietary fat intake with APOA2, APOA5 and LEPR polymorphisms and its relationship with obesity and dyslipidemia in young subjects.

BACKGROUND: Diet is an important environmental factor that interacts with genes to modulate the likelihood of developing disorders in lipid metabolism and the relationship between diet and genes in the presence of other chronic diseases such as obesity. The objective of this study was to analyze the interaction of a high fat diet with the APOA2 (rs3813627 and rs5082), APOA5 (rs662799 and rs3135506) and LEPR (rs8179183 and rs1137101) polymorphisms and its relationship with obesity and dyslipidemia in young subjects. METHODS: The study included 200 young subjects aged 18 to 25 years (100 normal-weight and 100 obese subjects). Dietary fat intake was measured using the frequency food consumption questionnaire. Genotyping of polymorphisms was performed by PCR-RFLP. RESULTS: Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption (OR = 2.7, p = 0.006) and/or total fat (OR = 2.4, p = 0.018), associated with an increased risk of obesity. We also found that A/G + G/G genotypes of the 668 A/G polymorphism in the LEPR gene with an intake ≥ 12 g/d of saturated fatty acids, have 2.9 times higher risk of obesity (p = 0.002), 3.8 times higher risk of hypercholesterolemia (p = 0.002) and 2.4 times higher risk of hypertriglyceridemia (p = 0.02), than those with an intake <12 g/d of saturated fatty acids. Similarly, LEPR 668 A/G + G/G carriers with a high fat total intake had 3.0 times higher risk of obesity (p = 0.002) and 4.1 times higher risk of hypercholesterolemia (p = 0.001). CONCLUSION: Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects.

Pressure tunes electrical resistivity by four orders of magnitude in amorphous Ge2Sb2Te5 phase-change memory alloy.

Ge-Sb-Te-based phase-change memory is one of the most promising candidates to succeed the current flash memories. The application of phase-change materials for data storage and memory devices takes advantage of the fast phase transition (on the order of nanoseconds) and the large property contrasts (e.g., several orders of magnitude difference in electrical resistivity) between the amorphous and the crystalline states. Despite the importance of Ge-Sb-Te alloys and the intense research they have received, the possible phases in the temperature-pressure diagram, as well as the corresponding structure-property correlations, remain to be systematically explored. In this study, by subjecting the amorphous Ge(2)Sb(2)Te(5) (a-GST) to hydrostatic-like pressure (P), the thermodynamic variable alternative to temperature, we are able to tune its electrical resistivity by several orders of magnitude, similar to the resistivity contrast corresponding to the usually investigated amorphous-to-crystalline (a-GST to rock-salt GST) transition used in current phase-change memories. In particular, the electrical resistivity drops precipitously in the P = 0 to 8 GPa regime. A prominent structural signature representing the underlying evolution in atomic arrangements and bonding in this pressure regime, as revealed by the ab initio molecular dynamics simulations, is the reduction of low-electron-density regions, which contributes to the narrowing of band gap and delocalization of trapped electrons. At P > 8 GPa, we have observed major changes of the average local structures (bond angle and coordination numbers), gradually transforming the a-GST into a high-density, metallic-like state. This high-pressure glass is characterized by local motifs that bear similarities to the body-centered-cubic GST (bcc-GST) it eventually crystallizes into at 28 GPa, and hence represents a bcc-type polyamorph of a-GST.

Synergistic effect of BMP9 and TGF-ß in the proliferation and differentiation of osteoblasts.

We investigated the synergistic effect of bone morphogenetic protein 9 (BMP9) and transforming growth factor (TGF)-b in the transformation of mesenchymal stem cells into osteoblasts. We evaluated the effect of BMP9 and TGF-b on the induction of osteoblast formation. Mitogen-activated protein kinase (MAPK) pathway-related proteins such as p38, extracellular receptor kinase 1/2, and c-Jun N-terminal kinase (JNK) were analyzed. The interactions between TGF-Smad and BMP-MAPK were also studied. BMP9 alone induced the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and enhanced phosphorylation of p38, extracellular receptor kinase 1/2, and JNK. TGF-b alone failed to induce transformation, but could increase the effect of BMP9. In this process the activation of Smad resulted in activation of the JNK pathway in the MAPK pathway. BMP9 induced osteogenesis of MSC differentiation through the MAKP pathway, while TGF-b contributed to BMP9 enhancement through the Smad-JNK pathway.