In the context of global aging, cardiovascular disease has become the number one cause of death among Chinese women. Lifestyle factors play an important role in the development of coronary heart ...disease, and as awareness of the pathophysiology of coronary atherosclerosis has increased, lifestyle interventions play an important role in reducing the risk of coronary heart disease. However, there is a lack of research on the factors affecting coronary heart disease in female populations. Strengthening health education for women with coronary heart disease, reducing the burden of disease, improving the quality of life, and developing reasonable prevention strategies are crucial. Based on the review of the literature, this study reviews the risk factors for coronary heart disease and provides a scientific basis for awareness and early prevention of coronary heart disease in women.
Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large ...selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Context. The origin and life-cycle of molecular clouds are still poorly constrained, despite their importance for understanding the evolution of the interstellar medium. Many large-scale surveys of ...the Galactic plane have been conducted recently, allowing for rapid progress in this field. Nevertheless, a sub-arcminute resolution global view of the large-scale distribution of molecular gas, from the diffuse medium to dense clouds and clumps, and of their relationshipto the spiral structure, is still missing. Aims. We have carried out a systematic, homogeneous, spectroscopic survey of the inner Galactic plane, in order to complement the many continuum Galactic surveys available with crucial distance and gas-kinematic information. Our aim is to combine this data set with recent infrared to sub-millimetre surveys at similar angular resolutions. Methods. The SEDIGISM survey covers 78 deg2 of the inner Galaxy (−60°≤ℓ≤ 18°, |b|≤ 0.5°) in the J = 2–1 rotational transition of 13CO. This isotopologue of CO is less abundant than 12CO by factors up to 100. Therefore, its emission has low to moderate optical depths, and higher critical density, making it an ideal tracer of the cold, dense interstellar medium. The data have been observed with the SHFI single-pixel instrument at APEX. The observational setup covers the 13CO(2−1) and C18O(2−1) lines, plus several transitions from other molecules. Results. The observations have been completed. Data reduction is in progress, and the final data products will be made available in the near future. Here we give a detailed description of the survey and the dedicated data reduction pipeline. To illustrate the scientific potential of this survey, preliminary results based on a science demonstration field covering −20°≤ℓ ≤ −18.5° are presented. Analysis of the 13CO(2−1) data in this field reveals compact clumps, diffuse clouds, and filamentary structures at a range of heliocentric distances. By combining our data with data in the (1–0) transition of CO isotopologues from the ThrUMMS survey, we are able to compute a 3D realization of the excitation temperature and optical depth in the interstellar medium. Ultimately, this survey will provide a detailed, global view of the inner Galactic interstellar medium at an unprecedented angular resolution of ~30′′.
Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the ...electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex
), electron-neutral (complex
), and electron-donating (complex
) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex
) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.
It is unclear whether, for the same amount of total physical activity, a higher proportion of vigorous physical activity (VPA) to total physical activity is associated with a greater reduction in ...mortality.
To examine the association of the proportion of VPA to total physical activity (defined as moderate to vigorous physical activity MVPA) with all-cause mortality, cardiovascular disease mortality, and cancer mortality.
This cohort study included 403 681 adults from the National Health Interview Survey 1997-2013 who provided data on self-reported physical activity and were linked to the National Death Index records through December 31, 2015. Statistical analysis was performed from May 15, 2018, to August 15, 2020.
Proportion of VPA to total physical activity among participants performing any MVPA.
All-cause mortality, cardiovascular disease mortality, and cancer mortality. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) and 95% CIs, adjusted for sociodemographic characteristics, lifestyle risk factors, and total physical activity.
Among the 403 681 individuals (225 569 women 51.7%; mean SD age, 42.8 16.3 years) in the study, during a median 10.1 years (interquartile range, 5.4-14.6 years) of follow-up (407.3 million person-years), 36 861 deaths occurred. Mutually adjusted models considering the recommendations of moderate physical activity (MPA; 150-299 vs 0 minutes per week) and VPA (≥75-149 vs 0 minutes per week) showed similar associations for all-cause mortality (MPA: HR, 0.83; 95% CI, 0.80-0.87; and VPA: HR, 0.80; 95% CI, 0.76-0.84) and cardiovascular disease mortality (MPA: HR, 0.75; 95% CI, 0.68-0.83; and VPA: HR, 0.79; 95% CI, 0.70-0.91). For the same contrasts, VPA (HR, 0.89; 95% CI, 0.80-0.99) showed a stronger inverse association with cancer mortality compared with MPA (HR, 0.94; 95% CI, 0.86-1.02). Among participants performing any MVPA, a higher proportion of VPA to total physical activity was associated with lower all-cause mortality but not with cardiovascular disease and cancer mortality. For instance, compared with participants with 0% of VPA (no vigorous activity), participants performing greater than 50% to 75% of VPA to total physical activity had a 17% lower all-cause mortality (hazard ratio, 0.83; 95% CI, 0.78-0.88), independent of total MVPA. The inverse association between proportion of VPA to total physical activity and all-cause mortality was consistent across sociodemographic characteristics, lifestyle risk factors, and chronic conditions at baseline.
This study suggests that, for the same volume of MVPA, a higher proportion of VPA to total physical activity was associated with lower all-cause mortality. Clinicians and public health interventions should recommend 150 minutes or more per week of MVPA but also advise on the potential benefits associated with VPA to maximize population health.
Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa ...subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear.
To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss.
We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair.
Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.
Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability ...may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death.
To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes.
Fifty-two organ procurement organizations provided US hospital policies pertaining to the criteria for determining brain death. Organizations were instructed to procure protocols specific to brain death (ie, not cardiac death or organ donation procedures). Data analysis was conducted from June 26, 2012, to July 1, 2015.
Policies were evaluated for summary statistics across the following 5 categories of data: who is qualified to perform the determination of brain death, what are the necessary prerequisites for testing, details of the clinical examination, details of apnea testing, and details of ancillary testing. We compared these data with the standards in the 2010 AAN update on practice parameters for brain death.
A total of 508 unique hospital policies were obtained, representing the majority of hospitals in the United States that would be eligible and equipped to evaluate brain death in a patient. Of these, 492 provided adequate data for analysis. Although improvement with AAN practice parameters was readily apparent, there remained significant variability across all 5 categories of data, such as excluding the absence of hypotension (276 of 491 policies 56.2%) and hypothermia (181 of 228 policies 79.4%), specifying all aspects of the clinical examination and apnea testing, and specifying appropriate ancillary tests and how they were to be performed. Of the 492 policies, 163 (33.1%) required specific expertise in neurology or neurosurgery for the health care professional who determines brain death, and 212 (43.1%) stipulated that an attending physician determine brain death; 150 policies did not mention who could perform such determination.
Hospital policies in the United States for the determination of brain death are still widely variable and not fully congruent with contemporary practice parameters. Hospitals should be encouraged to implement the 2010 AAN guidelines to ensure 100% accurate and appropriate determination of brain death.
Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here ...reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using a two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain super(39) Ar at a level reduced by a factor (1.4+ or -0.2)x10 super(3) relative to atmospheric argon. We report a background-free null result from (2616+ or -43)kgd of data, accumulated over 70.9 live days. When combined with our previous search using an atmospheric argon, the 90% C.L. upper limit on the WIMP-nucleon spin-independent cross section, based on zero events found in the WIMP search regions, is 2.0x10 super(-44)cm super(2)(8.6x10-44cm super(2), 8.0x10 super(-43)cm super(2)) for a WIMP mass of 100GeV/c super(2)(1TeV/c super(2), 10TeV/c super(2)).
The radiolysis of water is ubiquitous in nature and plays a critical role in numerous biochemical and technological applications. Although the elementary reaction pathways for ionized water have been ...studied, the short-lived intermediate complex and structural dynamic response after the proton transfer reaction remain poorly understood. Using a liquid-phase ultrafast electron diffraction technique to measure the intermolecular oxygen···oxygen and oxygen···hydrogen bonds, we captured the short-lived radical-cation complex OH(H
O
) that was formed within 140 femtoseconds through a direct oxygen···oxygen bond contraction and proton transfer, followed by the radical-cation pair dissociation and the subsequent structural relaxation of water within 250 femtoseconds. These measurements provide direct evidence of capturing this metastable radical-cation complex before separation, thereby improving our fundamental understanding of elementary reaction dynamics in ionized liquid water.
PDF
