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Social Science & Medicine (1982) Sep 2021The preponderance of research documents the negative consequences of racial discrimination for the mental and physical well-being across several racial/ethnic groups...
RATIONALE
The preponderance of research documents the negative consequences of racial discrimination for the mental and physical well-being across several racial/ethnic groups including Black Americans, Hispanic Americans, and Asian Americans. Despite this large body of research, few studies have attempted to evaluate racial discrimination as a casual factor of worse health among racial minority groups. The current study utilized nationally representative data to estimate the causal effect of racial discrimination on cardiovascular disease (CVD), self-rated physical health (SRH), body mass index (BMI), depression disorder, and substance use disorder. In addition, we examined whether the effect of racial discrimination on health was moderated by socio-demographic characteristics (i.e., age, race/ethnicity, sex, socioeconomic status, marital status, geographic location, and health insurance coverage).
METHODS
Data were from the combined National Survey of American Life and the National Latino and Asian American Study. We applied a propensity score weighting approach to estimate the differences between individuals who reported ever (N = 4358) or never (N = 1836) experiencing racial discrimination on a list of health outcomes (e.g., CVD, SRH, BMI, depression disorder, and substance use disorder).
RESULTS
Participants who reported ever experiencing racial discrimination were about 5 % higher CVD risk, had 0.12 points lower SRH, a 3 % higher probability of a depression disorder, and a 2 % higher probability of a substance use disorder. Moderation effects by race/ethnicity, sex, socioeconomic status, geographic region, and health insurance coverage were found.
CONCLUSION
Our study represents one of the first attempts to apply a propensity score weighting approach to causally link racial discrimination to worse health for racial minority individuals. This study adds to a larger body of research documenting the negative association between racial discrimination and health.
Topics: Black or African American; Asian; Hispanic or Latino; Humans; Propensity Score; Racism; United States
PubMed: 34399293
DOI: 10.1016/j.socscimed.2021.114308 -
Frontiers in Physiology 2021Alcohol-related liver disease (ALD) represents the most common liver disease worldwide, however, the underlying molecular mechanisms are still poorly understood. Namely...
INTRODUCTION
Alcohol-related liver disease (ALD) represents the most common liver disease worldwide, however, the underlying molecular mechanisms are still poorly understood. Namely centrilobular inflammation and programmed cell death are characteristic to ALD and it remains to be elucidated why they persist despite the absence of alcohol.
AIMS
To study the effects of alcohol withdrawal in a cohort of heavy drinkers and the role of cirrhosis by using non-invasive biomarkers such as cytokines, apoptotic and angiogenic markers.
METHODS
Caspase 3-cleaved M30, M65, cytokines (IL-6, IL-8), tumor necrosis factor alpha (TNF-α), transforming growth factor (TGF-β) and vascular endothelial growth factor (VEGF) were measured in 114 heavy drinkers. The role of alcohol detoxification was investigated in 45 patients. The liver histology was available in 23 patients. Fibrosis stage and steatosis were assessed by measuring liver stiffness (LS) and controlled attenuation parameter (CAP) in all patients using transient elastography (FibroScan, Echosens, Paris). Mean observation interval between the measurements was 5.7 ± 1.4 days (mean + -SD).
RESULTS
Patients consumed a mean of 204 ± 148 g/day alcohol with a heavy drinking duration of 15.3 ± 11.0 years. Mean LS was 20.7 ± 24.4 kPa and mean CAP was 303 ± 51 dB/m. Fibrosis distribution was F0-38.1%, F1-2-31%, F3-7.1 and F4-23.9%. Apoptotic markers M30 and M65 were almost five times above normal. In contrast, TNF- α a, IL-8 and VEGF were only slightly elevated. Patients with manifest liver cirrhosis (F4) had significantly higher levels of M30, M65, IL-6 and IL-8. Histology features such as hepatocyte ballooning, Mallory-Denk bodies, inflammation and fibrosis were all significantly associated with elevated LS, and serum levels of TNF-alpha, M30 and M65 but not with CAP and other cytokines. During alcohol detoxification, LS, transaminases, TGF- β, IL-6, IL-8 and VEGF decreased significantly. In contrast, no significant changes were observed for M30, M65 and TNF- α and M30 even increased during detoxification in non-cirrhotic patients. Profibrogenic cytokine TGF-beta and pro-angiogenic cytokine VEGF showed a delayed decrease in patients with manifest cirrhosis.
CONCLUSION
Patients with alcohol-related cirrhosis have a pronounced apoptotic activity and a distinct inflammatory response that only partly improves after 1 week of alcohol detoxification. Alcohol withdrawal may represent an important approach to better dissect the underlying mechanisms in the setting of alcohol metabolism.
PubMed: 34305638
DOI: 10.3389/fphys.2021.678118 -
Swiss Medical Weekly Jul 2021During the ongoing COVID-19 pandemic, the launch of a large-scale vaccination campaign and virus mutations have hinted at possible changes in transmissibility and the...
AIMS OF THE STUDY
During the ongoing COVID-19 pandemic, the launch of a large-scale vaccination campaign and virus mutations have hinted at possible changes in transmissibility and the virulence affecting disease progression up to critical illness, and carry potential for future vaccination failure. To monitor disease development over time with respect to critically ill COVID-19 patients, we report near real-time prospective observational data from the RISC-19-ICU registry that indicate changed characteristics of critically ill patients admitted to Swiss intensive care units (ICUs) at the onset of a third pandemic wave.
METHODS
1829 of 3344 critically ill COVID-19 patients enrolled in the international RISC-19-ICU registry as of 31 May 2021 were treated in Switzerland and were included in the present study. Of these, 1690 patients were admitted to the ICU before 1 February 2021 and were compared with 139 patients admitted during the emerging third pandemic wave RESULTS: Third wave patients were a mean of 5.2 years (95% confidence interval [CI] 3.2–7.1) younger (median 66.0 years, interquartile range [IQR] 57.0–73.0 vs 62.0 years, IQR 54.5–68.0; p <0.0001) and had a higher body mass index than patients admitted in the previous pandemic period. They presented with lower SAPS II and APACHE II scores, less need for circulatory support and lower white blood cell counts at ICU admission. P/F ratio was similar, but a 14% increase in ventilatory ratio was observed over time (p = 0.03) CONCLUSION: Near real-time registry data show that the latest COVID-19 patients admitted to ICUs in Switzerland at the onset of the third wave were on average 5 years younger, had a higher body mass index, and presented with lower physiological risk scores but a trend towards more severe lung failure. These differences may primarily be related to the ongoing nationwide vaccination campaign, but the possibility that changes in virus-host interactions may be a co-factor in the age shift and change in disease characteristics is cause for concern, and should be taken into account in the public health and vaccination strategy during the ongoing pandemic. (ClinicalTrials.gov Identifier: NCT04357275).
Topics: COVID-19; Critical Illness; Hospital Mortality; Humans; Intensive Care Units; Pandemics; Prevalence; Prospective Studies; SARS-CoV-2; Switzerland
PubMed: 34291810
DOI: 10.4414/smw.2021.20553 -
International Journal of Molecular... Jun 2021p62/Sequestosome-1 (p62) is a multifunctional adaptor protein and is also a constant component of disease-associated protein aggregates, including Mallory-Denk bodies...
p62/Sequestosome-1 (p62) is a multifunctional adaptor protein and is also a constant component of disease-associated protein aggregates, including Mallory-Denk bodies (MDBs), in steatohepatitis and hepatocellular carcinoma. We investigated the interaction of the two human p62 isoforms, p62-H1 (full-length isoform) and p62-H2 (partly devoid of PB1 domain), with keratins 8 and 18, the major components of MDBs. In human liver, p62-H2 is expressed two-fold higher compared to p62-H1 at the mRNA level and is present in slightly but not significantly higher concentrations at the protein level. Co-transfection studies in CHO-K1 cells, PLC/PRF/5 cells as well as p62 total-knockout and wild-type mouse fibroblasts revealed marked differences in the cytoplasmic distribution and aggregation behavior of the two p62 isoforms. Transfection-induced overexpression of p62-H2 generated large cytoplasmic aggregates in PLC/PRF/5 and CHO-K1 cells that mostly co-localized with transfected keratins resembling MDBs or (transfection without keratins) intracytoplasmic hyaline bodies. In fibroblasts, however, transfected p62-H2 was predominantly diffusely distributed in the cytoplasm. Aggregation of p62-H2 and p62ΔSH2 as well as the interaction with K8 (but not with K18) involves acquisition of cross-β-sheet conformation as revealed by staining with luminescent conjugated oligothiophenes. These results indicate the importance of considering p62 isoforms in protein aggregation disease.
Topics: Animals; CHO Cells; Cricetulus; Humans; Keratins; Mice; Mice, Knockout; Protein Aggregates; Protein Isoforms; Sequestosome-1 Protein
PubMed: 34207662
DOI: 10.3390/ijms22126227 -
Accounts of Chemical Research Jul 2021This Account describes a body of research in the design and synthesis of molecular materials prepared from corannulene. Corannulene (CH) is a molecular bowl of carbon...
This Account describes a body of research in the design and synthesis of molecular materials prepared from corannulene. Corannulene (CH) is a molecular bowl of carbon that can be visualized as the hydrogen-terminated cap of buckminsterfullerene. Due to this structural resemblance, it is often referred to as a buckybowl. The bowl can invert, accept electrons, and form host-guest complexes. Due to these characteristics, corannulene presents a useful building block in materials chemistry.In macromolecular science, for example, assembly of amphiphilic copolymers carrying a hydrophobic corannulene block enables micelle formation in water. Such micellar nanostructures can host large amounts of fullerenes (C and C) in their corannulene-rich core through complementarity of the curved π-surfaces. Covalent stabilization of the assembled structures then leads to the formation of robust water-soluble fullerene nanoparticles. Alternatively, use of corannulene in a polymer backbone allows for the preparation of electronic and redox-active materials. Finally, a corannulene core enables polymer chains to respond to solution temperature changes and form macroscopic fibrillar structures. In this way, the corannulene motif brings a variety of properties to the polymeric materials.In the design of non-fullerene electron acceptors, corannulene is emerging as a promising aromatic scaffold. In this regard, placement of sulfur atoms along the rim can cause an anodic shift in the molecular reduction potential. Oxidation of the sulfur atoms can further enhance this shift. Thus, a variation in the number, placement, and oxidation state of the sulfur atoms can create electron acceptors of tunable and high strengths. An advantage of this molecular design is that material solubility can also be tuned. For example, water-soluble electron acceptors can be created and are shown to improve the moisture resistance of perovskite solar cells.Host-guest complexation between corannulene and γ-cyclodextrin under flow conditions of a microfluidic chamber allows for the preparation of water-soluble nanoparticles. Due to an oligosaccharide-based sugarcoat, the nanoparticles are biocompatible while the corannulene component renders them active toward nonlinear absorption and emission properties. Together, these attributes allow the nanoparticles to be used as two-photon imaging probes in cancer cells.Finally, aromatic extension of the corannulene nucleus is seen as a potential route to nonplanar nanographenes. Typically, such endeavors rely upon gas-phase synthesis or metal-catalyzed coupling protocols. Recently, two new approaches have been established in this regard. Photochemically induced oxidative cyclization, the Mallory reaction, is shown to be a general method to access corannulenes with an extended π-framework. Alternatively, solid-state ball milling can achieve this goal in a highly efficient manner. These new protocols bring practicality and sustainability to the rapidly growing area of corannulene-based nanographenes.In essence, corannulene presents a unique building block in the construction of functional materials. In this Account, we trace our own efforts in the field and point toward the challenges and future prospects of this area of research.
PubMed: 34115472
DOI: 10.1021/acs.accounts.1c00207 -
Veterinary Medicine International 2021Mesenchymal stem cells-conditioned medium (MSC-CM) is the extraction from stem cell medium containing biological substances, including growth factors and cytokines....
Mesenchymal stem cells-conditioned medium (MSC-CM) is the extraction from stem cell medium containing biological substances, including growth factors and cytokines. These substances play roles in the various functions of body regulatory, including bone formation. However, the effect of MSC-CM derived from human umbilical cord injection in femur fracture healing of rats has not been reported previously. This study aims to see the effect of MSC-CM derived from human umbilical cord injection on the callus formation of bone fracture healing in Wistar rats (). A femur fracture in 54 Wistar rats was made by surgery according to the procedure under sterile conditions. After the surgery, rats were divided into 2 groups of 27, respectively. Injection in the control (0.1 mL/kg body weight NaCl) and MSC-CM group (0.1 mL/kg body weight MSC-CM) was performed on weeks 0, 1, 2, 3, 4, 5, 6, 7, and 8 after surgery. Radiographic images and the femur bone samples were taken and collected on days 1, 7, 14, 21, 28, 35, and 60 after surgery. Bone samples were then fixed in Bouin solution. Histologic preparations were done by the paraffin method, by cutting the tissue blocks into 5 m thickness and then staining with Mallory aniline blue staining. The results were analyzed descriptively and quantitatively. The result showed that the soft callus formation occurred rapidly and got wider in the MSC-CM group than that of the control group. The administration of MSC-CM injection postfracture surgery to femur fracture cases in rats was capable to accelerate the callus formation.
PubMed: 33996023
DOI: 10.1155/2021/8410175 -
Liver Transplantation : Official... Sep 2021The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is...
The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End-Stage Liver Disease-sodium (MELD-Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD-Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short-term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow-up are required.
Topics: Aged; Carcinoma, Hepatocellular; End Stage Liver Disease; Gastric Balloon; Humans; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Male; Severity of Illness Index; Weight Loss
PubMed: 33866660
DOI: 10.1002/lt.26074 -
LGBT Health 2021Sexual minority youth (SMY), particularly bisexual youth and youth unsure of their sexual identity, are at greater risk of poor mental and sexual health outcomes than...
Sexual minority youth (SMY), particularly bisexual youth and youth unsure of their sexual identity, are at greater risk of poor mental and sexual health outcomes than heterosexual youth. The purpose of this study was to examine disparities in intimate partner violence (IPV) and mental and sexual health for Black and Latino/a bisexual and unsure youth compared with their White bisexual and unsure and Black and Latino/a heterosexual peers. We used aggregated state and school district 2015 Youth Risk Behavior Survey data to demonstrate differences in mental health (e.g., depressive symptoms and suicidality), sexual health (e.g., number of sexual partners and contraceptive use), and physical and sexual IPV between Black and Latino/a bisexual and unsure youth, and their White bisexual and unsure and Black and Latino/a heterosexual peers. Bisexual and unsure youth had higher odds of depressive symptoms, suicidal ideation and plans, and physical IPV than their same-race heterosexual peers. Black and Latina bisexual and unsure females were more likely to report sexual health risk behaviors than Black and Latina heterosexual females. There were few differences between bisexual and unsure youth of color and White youth. We add to a growing body of literature showing disparities in IPV and mental and sexual health among bisexual and unsure youth of color. Pronounced risk for poor health outcomes among bisexual and unsure females of color needs to be especially addressed by prevention and intervention efforts. We encourage further research on the health of SMY with multiple marginalized identities.
Topics: Adolescent; Black or African American; Female; Health Status Disparities; Heterosexuality; Hispanic or Latino; Humans; Intimate Partner Violence; Male; Mental Health; Sexual Health; Sexual and Gender Minorities
PubMed: 33861625
DOI: 10.1089/lgbt.2020.0374 -
The American Journal of Gastroenterology Aug 2021Fatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North...
INTRODUCTION
Fatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North American cohort with chronic hepatitis B virus (HBV).
METHODS
Liver biopsies from 420 hepatitis B surface antigen-positive adults enrolled in the Hepatitis B Research Network and who were not on HBV therapy in the previous month were evaluated for inflammation and fibrosis. Steatohepatitis was based on steatosis, hepatocyte ballooning ± Mallory-Denk bodies, and perisinusoidal fibrosis. Models evaluated factors associated with steatohepatitis, and the associations of steatohepatitis with fibrosis, and longitudinal alanine aminotransferase, aspartate aminotransferase, and Fibrosis-4.
RESULTS
The median age was 42 years, 62.5% were male, and 79.5% were Asian. One hundred thirty-two (31.4%) patients had FLD (77 [18.3%] steatosis only, 55 [13.1%] steatohepatitis). Older age, overweight/obesity, and diabetes were associated with steatohepatitis. Steatohepatitis (vs no FLD) was associated with 1.68 times higher risk of advanced fibrosis at baseline (95% confidence interval, 1.12-2.51), and there was an indication of higher incident cirrhosis rate during follow-up. Steatohepatitis vs no FLD was also independently associated with, on average, 1.39 times higher alanine aminotransferase (P < 0.01) and 1.25 times higher Fibrosis-4 (P = 0.04) across 4 years.
DISCUSSION
Coexisting steatosis occurred in nearly a third of adults (13% had steatohepatitis) with chronic HBV in this North American cohort who underwent liver biopsies. Steatohepatitis was associated with advanced fibrosis and higher biochemical measures of hepatic inflammation over time. Therefore, in addition to viral suppression, screening for and managing metabolic abnormalities is important to prevent disease progression in HBV.
Topics: Adolescent; Adult; Age Factors; Aged; Biopsy; Disease Progression; Fatty Liver; Female; Hepatitis B, Chronic; Humans; Male; Middle Aged; North America; Risk Factors
PubMed: 33840726
DOI: 10.14309/ajg.0000000000001257 -
Medical Molecular Morphology Jun 2021Hepatitis C virus (HCV) infection has been known to use autophagy for its replication. However, the mechanisms by which HCV modulates autophagy remain controversial. We...
Hepatitis C virus (HCV) infection has been known to use autophagy for its replication. However, the mechanisms by which HCV modulates autophagy remain controversial. We used HCV-Japanese fulminant hepatitis-1-infected Huh7 cells. HCV infection induced the accumulation of autophagosomes. Morphological analyses of monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 transfection showed HCV infection impaired autophagic flux. Autophagosome-lysosome fusion assessed by transfection of mRFP- or GFP-LC3 and immunostaining of lysosomal-associated membrane protein 1 was inhibited by HCV infection. Decrease of HCV-induced endoplasmic reticulum (ER) stress by 4-phenylbutyric acid, a chemical chaperone, improved the HCV-mediated autophagic flux impairment. HCV infection-induced oxidative stress and subsequently DNA damage, but not apoptosis. Furthermore, HCV induced cytoprotective effects against the cellular stress by facilitating the formation of cytoplasmic inclusion bodies as shown by p62 expression and by modulating keratin protein expression and activated nuclear factor erythroid 2-related factor 2. HCV eradication by direct-acting antivirals improved autophagic flux, but DNA damage persisted. In conclusion, HCV-induced ER stress correlates with autophagic flux impairment. Decrease of ER stress is considered to be a promising therapeutic strategy for HCV-related chronic liver diseases. However, we should be aware that the risk of hepatocarcinogenesis remains even after HCV eradication.
Topics: Autophagy; Carcinogenesis; Cell Line; Endoplasmic Reticulum Stress; Gene Expression Regulation; Hepatitis C; Humans; Keratins; Liver; Liver Neoplasms; NF-E2-Related Factor 2
PubMed: 33386512
DOI: 10.1007/s00795-020-00271-5