Anesthesia for cesarean delivery and subsequent depression: A nationwide retrospective cohort study.

BACKGROUND: Postpartum depression is a major psychiatric disorder associated with maternal suicide and child developmental disturbances. In this study, we aimed to investigate whether general anesthesia for cesarean delivery is associated with a higher rate of new-onset depression after delivery than neuraxial anesthesia. METHODS: This is a nationwide retrospective cohort study using data retrieved from the National Health Insurance Research Database between 2014 and 2018. Women who had cesarean delivery under general or neuraxial anesthesia were enrolled. After 1:4 propensity score matching, there were 4544 and 18,176 women under the general and neuraxial anesthesia groups, respectively. The primary outcome was new-onset depression diagnosed after delivery in a time-to-event analysis setting. RESULTS: After propensity-score matching, the rate of new-onset depression diagnosed within 1 year was 1.10 % (50/4488) and 0.86 % (157/18176) after cesarean delivery under general and neuraxial anesthesia, respectively. For depression diagnosed within 90 days of delivery, significant difference between the two groups was noted (0.51 % vs. 0.30 %, P = 0.031). In the time-to-event analysis with Cox regression model, women who delivered under general anesthesia were associated with significantly higher risk of postpartum depression within 90 days (Hazard ratio [HR], 1.71; 95 % CI, 1.05-2.79) compared with those under neuraxial anesthesia. LIMITATIONS: The observational design only allows asserting association, rather than establishing causality between exposure and outcomes. CONCLUSIONS: Women who underwent cesarean delivery under general anesthesia had a higher risk of subsequent depression within 90 days than those under neuraxial anesthesia. Early screening for depressive disorders might facilitate timely management.

[A highly sensitive approach for the analysis of tyrosine phosphoproteome in primary T cells].

Tyrosine phosphorylation, a common post-translational modification process for proteins, is involved in a variety of biological processes. However, the abundance of tyrosine-phosphorylated proteins is very low, making their identification by mass spectrometry (MS) is difficult; thus, milligrams of the starting material are often required for their enrichment. For example, tyrosine phosphorylation plays an important role in T cell signal transduction. However, the number of primary T cells derived from biological tissue samples is very small, and these cells are difficult to culture and expand; thus, the study of T cell signal transduction is usually carried out on immortalized cell lines, which can be greatly expanded. However, the data from immortalized cell lines cannot fully mimic the signal transduction processes observed in the real physiological state, and they usually lead to conclusions that are quite different from those of primary T cells. Therefore, a highly sensitive proteomic method was developed for studying tyrosine phosphorylation modification signals in primary T cells. To address the issue of the limited T cells numbers, a comprehensive protocol was first optimized for the isolation, activation, and expansion of primary T cells from mouse spleen. CD3+ primary T cells were successfully sorted; more than 91% of the T cells collected were well activated on day 2, and the number of T cells expanded to over 7-fold on day 4. Next, to address the low abundance of tyrosine-phosphorylated proteins, we used SH2-superbinder affinity enrichment and immobilized Ti4+affinity chromatography (Ti4+-IMAC) to enrich the tyrosine-phosphorylated polypeptides of primary T cells that were co-stimulated with anti-CD3 and anti-CD28. These polypeptides were resolved using nanoscale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Finally, 282 tyrosine phosphorylation sites were successfully identified in 1 mg of protein, including many tyrosine phosphorylation sites on the immunoreceptor tyrosine-based activation motif (ITAM) in the intracellular region of the T cell receptor membrane protein CD3, as well as the phosphotyrosine sites of ZAP70, LAT, VAV1, and other proteins related to signal transduction under costimulatory conditions. In summary, to solve the technical problems of the limited number of primary cells, low abundance of tyrosine-phosphorylated proteins, and difficulty of detection by MS, we developed a comprehensive proteomic method for the in-depth analysis of tyrosine phosphorylation modification signals in primary T cells. This protocol may be applied to map signal transduction networks that are closely related to physiological states.

Long range regulation of transcription scales with genomic distance in a gene specific manner.

While critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here we bypass the need for sequence-specific transcription factors and recruit activators directly using CARGO-VPR, an approach for targeting dCas9-VPR using a multiplexed array of RNA guides. We show that this approach achieves effective activator recruitment to arbitrary genomic sites, even those inaccessible by single dCas9. We utilize CARGO-VPR across the Prdm8-Fgf5 locus in mESCs, where neither gene is expressed. We demonstrate that while activator recruitment to any tested region results in transcriptional induction of at least one gene, the expression level strongly depends on the genomic distance between the promoter and activator recruitment site. However, the expression-distance relationship for each gene scales distinctly in a manner not attributable to differences in 3D contact frequency, promoter DNA sequence or presence of the repressive chromatin marks at the locus.

Association Between Osteoporosis and Adiposity Index Reveals Nonlinearity Among Postmenopausal Women and Linearity Among Men Aged over 50 Years.

PURPOSE: Previous research shows conflicting views on the relationship between obesity and osteoporosis, partly due to variations in obesity classification and the nonlinear nature of these relationships. This study investigated the association between adiposity indices and osteoporosis, diagnosed using dual-energy X-ray absorptiometry (DXA), employing nonlinear models and offering optimal thresholds to prevent further bone mineral density decline. METHODS: In 2019, a prospective study enrolled males over 50 years and postmenopausal women. Anthropometric measurements, blood biochemistry, and osteoporosis measured by DXA were collected. Associations between adiposity indices and osteoporosis were analyzed using a generalized additive model and segmented regression model. RESULTS: The study included 872 women and 1321 men. Indices such as abdominal volume index (AVI), visceral adiposity index (VAI), waist circumference (WC), hip circumference, body mass index (BMI), waist-to-hip ratio, and waist-to-height ratio (WHtR) were inversely associated with osteoporosis. In women, the relationship between the risk of osteoporosis and the adiposity indices was U-shaped, with thresholds of WC = 94 cm, AVI = 17.67 cm2, BMI = 25.74 kg/m2, VAI = 4.29, and WHtR = 0.61, considering changes in bone mineral density. Conversely, men exhibited a linear patterns for the inverse association. CONCLUSION: The impact of obesity and adiposity on osteoporosis varies significantly between women and men. In postmenopausal women, the relationship is nonlinear (U-shaped), with both very low and very high adiposity linked to higher osteoporosis risk. In men over 50, the relationship is linear, with higher adiposity associated with lower osteoporosis risk. The study suggests that maintaining specific levels of adiposity could help prevent osteoporosis in postmenopausal women.

Induced proximity labeling and editing for epigenetic research.

Epigenetic regulation plays a pivotal role in various biological and disease processes. Two key lines of investigation have been pursued that aim to unravel endogenous epigenetic events at particular genes (probing) and artificially manipulate the epigenetic landscape (editing). The concept of induced proximity has inspired the development of powerful tools for epigenetic research. Induced proximity strategies involve bringing molecular effectors into spatial proximity with specific genomic regions to achieve the probing or manipulation of local epigenetic environments with increased proximity. In this review, we detail the development of induced proximity methods and applications in shedding light on the intricacies of epigenetic regulation.

Ambient-Light-Promoted Stereospecific Synthesis of (Z)-Vinyl Thioesters under Solvent- and Catalyst-Free Conditions.

An ambient-light-promoted stereospecific olefinic C(sp2)-S bond construction of thioacids and 1,1-diarylethenes has been demonstrated, affording various (Z)-vinyl thioesters in 51-85% yields under solvent- and catalyst-free conditions. Mechanistic studies indicated that the formation of thioacid-olefin complexes is responsible for generating a carbonyl thiyl radical and dioxygen in the air participates in the reaction and functions as a traceless reagent. Moreover, synthetic applications have been demonstrated by the gram scale synthesis and aggregation-induced emission property of representative compound 3i.

Risk of Atrial Fibrillation in Patients with Different Cancer Types in Taiwan.

Atrial fibrillation (AF) commonly occurs in approximately 2% of cancer patients, and the incidence of AF among cancer patients is greater than in the general population. This observational study presented the incidence risk of AF among cancer patients, including specific cancer types, using a population database. The Taiwan Cancer Registry was used to identify cancer patients between 2008 and 2017. The diagnosis of AF was based on the International Classification of Diseases codes (ICD-9-CM: 427.31 or ICD-10-CM: I48.0, I48.1, I48.2, and I48.91) in Taiwan national health insurance research datasets. The incidence of developing AF in the cancer population was calculated as the number of new-onset AF cases per person-year of follow-up during the study period. The overall incidence of AF among cancer patients was 50.99 per 100,000 person-years. Patients aged older than 65 years and males had higher AF incidence rates. Lung cancer males and esophageal cancer females showed the highest AF incidence risk (185.02 and 150.30 per 100,000 person-years, respectively). Our findings identified esophageal, lung, and gallbladder cancers as the top three cancers associated with a higher incidence of AF. Careful monitoring and management of patients with these cancers are crucial for early detection and intervention of AF.

Inequalities in women's health insurance coverage before and after the implementation of universal health insurance in Indonesia.

Indonesia implemented a National Social Security System (Jaminan Kesehatan Nasional, JKN) in 2014. To examine the changes in the magnitude of socioeconomic inequity in women's health insurance coverage among those of reproductive age, we conducted a repeated cross-sectional study design using data from the Indonesia Demographic and Health Surveys conducted in 2012 and 2017, before and after the implementation of JKN. Results showed that while the JKN program helped to increase health insurance coverage among Indonesian women of childbearing age, low education level and household wealth status were associated with an increase in inequalities in health insurance coverage. The findings highlight the need to sustain coverage for citizens and to extend the JKN program to informal workers to reduce health coverage disparities. Further research is required to explore the mechanisms responsible for health coverage inequality based on socioeconomic indicators.

Aggregation induced emission dynamic chiral europium(III) complexes with excellent circularly polarized luminescence and smart sensors.

The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S-Eu-R-1, R = Et/Me; R/S-Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5D0 → 7F1) and 2429 M-1cm-1 of R-Eu-Et-1, achieving a rare double improvement. R-Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

Enhancing indicator condition-guided HIV testing in Taiwan: a nationwide case-control study from 2009 to 2015.

BACKGROUND: Although indicator condition (IC)-guided HIV testing (IC-HIVT) is effective at facilitating timely HIV diagnosis, research on IC categories and the related HIV risk in Taiwan is limited. To improve the adoption and spread of IC-HIVT in Taiwan, this study compared the IC categories of people living with HIV (PLWH) and non-HIV controls and investigated delays in the diagnosis of HIV infection. METHODS: This nationwide, retrospective, 1:10-matched case-control study analyzed data from the Notifiable Diseases Surveillance System and National Health Insurance Research Database to evaluate 42 ICs for the 5-year period preceding a matched HIV diagnostic date from 2009 to 2015. The ICs were divided into category 1 ICs (AIDS-defining opportunistic illnesses [AOIs]), category 2 ICs (diseases associated with impaired immunity or malignancy but not AOIs), category 3 ICs (ICs associated with sexual behaviors), and category 4 ICs (mononucleosis or mononucleosis-like syndrome). Logistic regression was used to evaluate the HIV risk associated with each IC category (at the overall and annual levels) before the index date. Wilcoxon rank-sum test was performed to assess changes in diagnostic delays following an incident IC category by HIV transmission routes. RESULTS: Fourteen thousand three hundred forty-seven PLWH were matched with 143,470 non-HIV controls. The prevalence results for all ICs and category 1-4 ICs were, respectively, 42.59%, 11.16%, 15.68%, 26.48%, and 0.97% among PLWH and 8.73%, 1.05%, 4.53%, 3.69%, and 0.02% among non-HIV controls (all P < 0.001). Each IC category posed a significantly higher risk of HIV infection overall and annually. The median (interquartile range) potential delay in HIV diagnosis was 15 (7-44), 324.5 (36-947), 234 (13-976), and 74 (33-476) days for category 1-4 ICs, respectively. Except for category 1 for men who have sex with men, these values remained stable across 2009-2015, regardless of the HIV transmission route. CONCLUSIONS: Given the ongoing HIV diagnostic delay, IC-HIVT should be upgraded and adapted to each IC category to enhance early HIV diagnosis.

Decomposing and simplifying the Fracture Risk Assessment Tool-a module from the Taiwan-specific calculator.

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8 years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1 g/cm2, the T-score was -1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.

Different anion (NO3- and OAc-)-controlled construction of dysprosium clusters with different shapes.

The complex hydrolysis process and strong uncertainty of self-assembly rules have led to the precise synthesis of lanthanide clusters still being in the "blind-box" stage and simplifying the self-assembly process and developing reliable regulation strategies have attracted widespread attention. Herein, different anions are used to induce the construction of a series of dysprosium clusters with different shapes and connections. When the selected anion is NO3-, it blocks the coordination of metal sites around the cluster through the terminal group coordination mode, thereby controlling the growth of the cluster. When NO3- was changed to OAc-, OAc- adopted a bridging mode to induce modular units to build dysprosium clusters through an annular growth mechanism. Specifically, we selected 2-amino-6-methoxybenzoic acid, 2-hydroxybenzaldehyde, and Dy(NO3)3·6H2O to react under solvothermal conditions to obtain a pentanuclear dysprosium cluster (1). The five Dy(III) ions in 1 are distributed in upper and lower planes and are formed by the tight connection of nitrogen and oxygen atoms, and µ3-OH- bridges on the ligand. Next, octa-nuclear dysprosium cluster (2) were obtained by only regulating ligand substituents. The eight Dy(III) ions in 2 are tightly connected through ligand oxygen atoms, µ2-OH-, and µ3-OH- bridges, forming an elliptical {Dy/O} cluster core. Furthermore, only by changing NO3- to OAc-, a wheel-shaped tetradeca-nuclear dysprosium cluster (3) was obtained. Cluster 3 is composed of OAc- bridged multiple template Dy3L3 units and pulling of these template units connected by an annular growth mechanism forms a wheel-shaped cluster. The angle of the coordination site on NO3- is ∠ONO = 115°, which leads to the further extension of the metal sites on the periphery of clusters 1 and 2 through the terminal group coordination mode, thereby regulating the structural connection of the clusters. However, the angle of the coordination site on OAc- is ∠OCO = 128°, and a slightly increased angle leads to the formation of a ring-shaped cluster 3 by connecting the template units through bridging. This is a rare example of the controllable construction of lanthanide clusters with different shapes induced by the regulation of different anions, which provides a new method for the precise construction of lanthanide clusters with special shapes.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Membrane protein chaperone and sodium chloride modulate the kinetics and morphology of amyloid beta aggregation.

Protein aggregation is a biological phenomenon caused by the accumulation of misfolded proteins. Amyloid beta (Aß) peptides are derived from the cleavage of a larger membrane protein molecule and accumulate to form plaques extracellularly. According to the amyloid hypothesis, accumulation of Aß aggregates in the brain is primarily responsible for the pathogenesis of Alzheimer's disease (AD). Therefore, the disassembly of Aß aggregates may provide opportunities for alleviating or treating AD. Here, we show that the novel protein targeting machinery from chloroplast, chloroplast signal recognition particle 43 (cpSRP43), is an ATP-independent membrane protein chaperone that can both prevent and reverse Aß aggregation effectively. Using of thioflavin T dye, we obtained the aggregation kinetics of Aß aggregation and determined that the chaperone prevents Aß aggregation in a concentration-dependent manner. Size exclusion chromatography and sedimentation assays showed that 10-fold excess of cpSRP43 can keep Aß in the soluble monomeric form. Electron microscopy showed that the fibril structure was disrupted in the presence of this chaperone. Importantly, cpSRP43 utilizes the binding energy to actively remodel the preformed Aß aggregates without assistance by a co-chaperone and ATP, emphasizing its unique function among protein chaperones. Moreover, when sodium chloride concentration is higher than 25 mm, the Aß aggregation rate increases drastically to form tightly associated aggregates and generate more oligomers. Our results demonstrate that the presence of cpSRP43 and low NaCl levels inhibit or retard Aß peptide aggregation, potentially opening new avenues to strategically develop an effective treatment for AD.

Expressions of cytokines and procalcitonin in infective endocarditis / 局解手术学杂志

Objective To investigate the expressions of 12 cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-α,IFN-γ,TNF-α)and procalcitonin in patients with infective endocarditis(IE).Methods Ten IE patients admitted to our hospital from December 2021 to December 2022 were included into the IE group,10 patients with non-infectious and non-rheumatic valvular diseases who were admitted to our hospital at the same period were randomly selected as the control group,and blood sampling of all patients were conducted at admission.The expressions of 12 cytokines and blood routine indexes were detected by flow cytometry,and the level of procalcitonin was detected by ELISA.The correlations among the expression levels of cytokines in IE patients were analyzed by Pearson method and the correlations of IL-8 level and white blood cell count with procalcitonin in IE patients were analyzed by Spearman method.Results Compared with the control group,the levels of cytokines of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ and IL-12p70 in the IE group were significantly increased(P<0.05),the white blood cell count,neutrophil percentage and procalcitonin were significantly increased(P<0.05).There was no significant difference in the percentage of monocytes between the two groups(P>0.05).IFN-α of IE patients was positively correlated with IL-2,TNF-α,IL-1β and IL-12p70,IL-2 was positively correlated with TNF-α and IL-1β,IL-12p70 was positively correlated with IFN-γ,and procalcitonin was significantly positively correlated with IL-8 and white blood cell count,with statistically significant differences(P<0.05).Conclusion The levels of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ,IL-12p70 and procalcitonin in IE patients are significantly higher than those in the normal population,and the detections of these indicators are of guiding significance for the early diagnosis of IE and the evaluation of the severity of the disease.

Determinants of cancer incidence and mortality among people with vitamin D deficiency: an epidemiology study using a real-world population database.

Introduction: This study aimed to investigate the determinants of cancer incidence and mortality in patients with vitamin D deficiency using a real-world population database. Methods: We utilized the International Diagnostic Classification Code (ICD9:268 / ICD10: E55) to define patients with vitamin D deficiency. Additionally, the Cox regression model was used to estimate overall mortality and identify potential factors contributing to mortality in cancer patients. Results: In 5242 patients with vitamin D deficiency, the development of new-onset cancer was 229 (4.37%) patients. Colon cancer was the most prevalent cancer type. After considering confounding factors, patients aged 50-65 and more than 65 indicated a 3.10-fold (95% C.I.: 2.12-4.51) and 4.55-fold (95% C.I.: 3.03-6.82) cancer incidence, respectively compared with those aged <50. Moreover, patients with comorbidities of diabetes mellitus (DM) (HR: 1.56; 95% C.I.: 1.01-2.41) and liver disease (HR: 1.62; 95% C.I.: 1.03-2.54) presented a higher cancer incidence rate than those without DM/ liver disease. In addition, vitamin D deficiency patients with cancer and dementia histories indicated a significantly higher mortality risk (HR: 4.04; 95% C.I.: 1.05- 15.56) than those without dementia. Conclusion: In conclusion, our study revealed that vitamin D deficiency patients with liver disease had an increased incidence of cancer, while those with dementia had an increased mortality rate among cancer patients.

Trend Analysis of Palliative Care Utilization in Patients with Chronic Obstructive Pulmonary Disease During Hospitalization from 2007 to 2018 in Taiwan.

Purpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD. Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan's National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization. Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions-especially cancer-and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1-2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1-2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years. Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.

Sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation can significantly improve cerebral hemodynamic perfusion.

PURPOSE: To investigate the effect of sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation on cerebral hemodynamic perfusion. MATERIALS AND METHODS: Patients with severe vascular stenosis of the posterior circulation who had undergone three-dimensional cerebral angiography before and after stenting were retrospectively enrolled. Computational fluid dynamic (CFD) analysis of hemodynamic parameters at the stenosis, perforating branch, and normal arterial segments proximal and distal to the stenosis were performed. RESULTS: Sixty-two patients with basilar artery stenosis aged 60.9 ±â€¯9.6 years were enrolled, and stent angioplasty resulted in the reduction of stenosis degree from 85.3 ±â€¯7.2% before to 18.6 ±â€¯6.4% after stenting. After stenting, at the proximal normal artery, the total pressures had significantly (P < 0.05) decreased, whereas all the other parameters (WSS, cell Reynolds number, velocity, vorticity, turbulence intensity, turbulence kinetic energy and dissipation rate) had significantly (P < 0.05) increased. At the stenosis, all hemodynamic parameters had significantly decreased. At the stenosis perforating branch, the WSS, cell Reynolds number, velocity, and vorticity were all significantly decreased, and the total pressure, turbulence intensity, kinetic energy, and dissipation rate were all significantly increased. At the distal normal artery, the total flow pressure (perfusion pressure) and velocity were both significantly (P < 0.05) increased, and the total pressure, WSS, cell Reynolds number, vorticity, turbulence intensity, kinetic energy, and dissipation rate were all significantly (P < 0.05) decreased. The hemodynamic parameters after stenting were closer to those after virtual stenosis repair at all measurements. CONCLUSION: Sub-satisfactory recanalization has significantly restored the stenosis and improved the hemodynamic parameters near the stenosis and at the root of the perforating branch, thus significantly improving the cerebral perfusion, similar to the changes of hemodynamic status and cerebral perfusion after virtual removal of the vascular stenosis. This may indicate the good effect of sub-satisfactory stenting recanalization of the vascular stenosis at the posterior circulation.

Topology regulatory elements: From shaping genome architecture to gene regulation.

The importance of 3D genome topology in the control of gene expression is becoming increasingly apparent, while regulatory mechanisms remain incompletely understood. Several recent studies have identified architectural elements that influence developmental gene expression by shaping locus topology. We refer to these elements as topological regulatory elements (TopoREs) to reflect their dual roles in genome organisation and gene expression. Importantly, these elements do not harbour autonomous transcriptional activation capacity, and instead appear to facilitate enhancer-promoter interactions, contributing to robust and precise timing of transcription. We discuss examples of TopoREs from two classes that are either dependent or independent of CTCF binding. Importantly, identification and interpretation of TopoRE function may shed light on multiple aspects of gene regulation, including the relationship between enhancer-promoter proximity and transcription, and enhancer-promoter specificity. Ultimately, understanding TopoRE diversity and function will aid in the interpretation of how human sequence variation can impact transcription and contribute to disease phenotypes.