Publications by authors named "Garima Sharma"

181 Publications

Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities.

Nat Commun 2021 06 14;12(1):3611. Epub 2021 Jun 14.

Division of Integrative Biosciences and Biotechnology, Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

Yeast is an integral part of mammalian microbiome, and like commensal bacteria, has the potential of being harnessed to influence immunity in clinical settings. However, functional specificities of yeast-derived immunoregulatory molecules remain elusive. Here we find that while under steady state, β-1,3-glucan-containing polysaccharides potentiate pro-inflammatory properties, a relatively less abundant class of cell surface polysaccharides, dubbed mannan/β-1,6-glucan-containing polysaccharides (MGCP), is capable of exerting potent anti-inflammatory effects to the immune system. MGCP, in contrast to previously identified microbial cell surface polysaccharides, through a Dectin1-Cox2 signaling axis in dendritic cells, facilitates regulatory T (Treg) cell induction from naïve T cells. Furthermore, through a TLR2-dependent mechanism, it restrains Th1 differentiation of effector T cells by suppressing IFN-γ expression. As a result, administration of MGCP display robust suppressive capacity towards experimental inflammatory disease models of colitis and experimental autoimmune encephalomyelitis (EAE) in mice, thereby highlighting its potential therapeutic utility against clinically relevant autoimmune diseases.
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http://dx.doi.org/10.1038/s41467-021-23929-9DOI Listing
June 2021

Association of Angiotensin Receptor Autoantibodies With Cardiovascular Abnormalities in Preeclampsia.

J Am Heart Assoc 2021 Jun 5;10(12):e020831. Epub 2021 Jun 5.

Division of Maternal-Fetal Medicine Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine Baltimore MD.

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http://dx.doi.org/10.1161/JAHA.121.020831DOI Listing
June 2021

GPx-1-encoded adenoviral vector attenuates dopaminergic impairments induced by methamphetamine in GPx-1 knockout mice through modulation of NF-κB transcription factor.

Food Chem Toxicol 2021 Jun 1;154:112313. Epub 2021 Jun 1.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea. Electronic address:

We suggested that selenium-dependent glutathione peroxidase (GPx) plays a protective role against methamphetamine (MA)-induced dopaminergic toxicity. We focused on GPx-1, a major selenium-dependent enzyme and constructed a GPx-1 gene-encoded adenoviral vector (Ad-GPx-1) to delineate the role of GPx-1 in MA-induced dopaminergic neurotoxicity. Exposure to Ad-GPx-1 significantly induced GPx activity and GPx-1 protein levels in GPx-1-knockout (GPx-1-KO) mice. MA-induced dopaminergic impairments [i.e., hyperthermia; increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) DNA-binding activity; and decreased dopamine levels, TH activity, and behavioral activity] were more pronounced in GPx-1-KO mice than in WT mice. In contrast, exposure to Ad-GPx-1 significantly attenuated MA-induced dopaminergic loss in GPx-1-KO mice. The protective effect exerted by Ad-GPx-1 was comparable to that exerted by pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor against MA insult. Consistently, GPx-1 overexpression significantly attenuated MA dopaminergic toxicity in mice. PDTC did not significantly impact the protective effect of GPx-1 overexpression, suggesting that interaction between NF-κB and GPx-1 is critical for dopaminergic protection. Thus, NF-κB is a potential therapeutic target for GPx-1-mediated dopaminergic protective activity. This study for the first time demonstrated that Ad-GPx-1 rescued dopaminergic toxicity in vivo following MA insult. Furthermore, GPx-1-associated therapeutic interventions may be important against dopaminergic toxicity.
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http://dx.doi.org/10.1016/j.fct.2021.112313DOI Listing
June 2021

Systematic Development and Characterization of Novel, High Drug-Loaded, Photostable, Curcumin Solid Lipid Nanoparticle Hydrogel for Wound Healing.

Antioxidants (Basel) 2021 May 5;10(5). Epub 2021 May 5.

Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.

The study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure homogenization, without using organic solvents, were optimized using the Taguchi design followed by the central composite design. The optimized CSLNs exhibited a high assay/drug content (0.6% /), solubility (6 × 10 times), and EE (75%) with a particle size < 200 nm (PDI-0.143). The CSLNs were safe (in vitro and in vivo), photostable, autoclavable, stable up to one year at 30 °C and under refrigeration and exhibited a controlled release (zero-order; 5 days). XRD, FTIR, and DSC confirmed solubilization and entrapment of the curcumin within the SLNs. TEM and FESEM revealed a smooth and spherical shape. The CSLNs showed a significant antimicrobial effect (MIC of 64 µg/mL for planktonic cells; 512 µg/mL for biofilm formation; and 2 mg/mL for mature biofilm) against 9144, while free curcumin dispersion did not exhibit any effect. This is the first report on the disruption of mature biofilms by curcumin solid lipid nanoparticles (CSLNs). The cell proliferation potential of CSLNs was also evaluated in vitro while the wound healing potential of CSLNs (incorporated in a hydrogel) was assessed in vivo. In (i) nitrogen mustard gas and (ii) a full-thickness excision wound model, CSLNs exhibited (a) significantly faster wound closure, (b) histologically and immunohistochemically better healing, (c) lower oxidative stress (LPO) and (d) inflammation (TNFα), and (e) increased angiogenesis (VEGF) and antioxidant enzymes, i.e., catalase and GSH levels. CSLNs thus offer a promising modern wound therapy especially for infected wounds, considering their effects in mature biofilm disruption.
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http://dx.doi.org/10.3390/antiox10050725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148018PMC
May 2021

Evaluating the efficacy of nitazoxanide in uncomplicated amebic liver abscess.

Indian J Gastroenterol 2021 Jun 15;40(3):272-280. Epub 2021 May 15.

Department of Gastroenterology, SMS Medical College and Hospital, Jaipur 302 004, India.

Background: Amebic liver abscess is treated successfully with metronidazole or another nitroimidazole drug followed by a luminal amebicide. Metronidazole has long been preferred, but has been associated with several adverse effects including intolerance in certain clinical situations. Mechanisms of metronidazole resistance and mutagenic potential have been described. Effects of the use of drug in pregnant women and infants of lactating women are unknown. Nitazoxanide was proven to be efficacious in treating invasive intestinal amebiasis. Therefore, the present study was undertaken to assess the efficacy and safety of nitazoxanide as compared to metronidazole in patients with uncomplicated amebic liver abscess.

Methods: Patients with clinical and ultrasonography features suggestive of liver abscess, positive amebic serology, and/or anchovy sauce appearance on aspiration of the pus were included in the study and randomized into two parallel treatment groups. Group M received metronidazole, 2-2.5 g/day intravenous (IV), for inpatients, or 2-2.4 g/day oral, for outpatients in three divided doses for 14 days. Group N received nitazoxanide 500 mg BD per oral for 10 days.

Results: A total of sixty subjects fulfilling the inclusion criteria were randomized equally into two groups, group M and group N. Number of patients achieving symptomatic clinical response (SCR) was similar in the two groups (80% vs. 76.7%, p = 1.00), though time to achieve symptomatic clinical response was significantly lower in metronidazole group as compared to that in nitazoxanide group. Greater proportion of patients achieved early clinical response (ECR) in metronidazole group as compared to nitazoxanide group. Complete resolution of abscess, at 6 months, was noted in 18 (60%) patients in the M group and 22 (73.3%) patients in the N group (p = 0.273). Metronidazole was associated with significantly greater frequency of adverse effects than nitazoxanide.

Conclusions: This study shows equivalent efficacy of nitazoxanide in uncomplicated amebic liver abscess as compared to metronidazole, with better tolerability and advantage of simultaneous luminal clearance, thus reducing chances of recurrence.

Trial Registration: CTRI/2019/01/017249.
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http://dx.doi.org/10.1007/s12664-020-01132-wDOI Listing
June 2021

Global Prevalence and Impact of Hostility, Discrimination, and Harassment in the Cardiology Workplace.

J Am Coll Cardiol 2021 May;77(19):2398-2409

Division of Cardiology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: Discrimination and emotional and sexual harassment create a hostile work environment (HWE). The global prevalence of HWE in cardiology is unknown, as is its impact.

Objectives: This study sought to evaluate emotional harassment, discrimination, and sexual harassment experienced by cardiologists and its impact on professional satisfaction and patient interactions worldwide.

Methods: The American College of Cardiology surveyed cardiologists from Africa, Asia, the Caribbean, Eastern Europe, the European Union, the Middle East, Oceana, and North, Central, and South America. Demographics, practice information, and HWE were tabulated and compared, and their impact was assessed. The p values were calculated using the chi-square, Fisher exact, and Mann-Whitney U tests. Univariate and multivariate logistic regression analysis determined the association of characteristics with HWE and its subtypes.

Results: Of 5,931 cardiologists (77% men; 23% women), 44% reported HWE. Higher rates were found among women (68% vs. 37%; odds ratio [OR]: 3.58 vs. men), Blacks (53% vs. 43%; OR: 1.46 vs. Whites), and North Americans (54% vs. 38%; OR: 1.90 vs. South Americans). Components of HWE included emotional harassment (29%; n = 1,743), discrimination (30%; n = 1,750), and sexual harassment (4%; n = 221), and they were more prevalent among women: emotional harassment (43% vs. 26%), discrimination (56% vs. 22%), and sexual harassment (12% vs. 1%). Gender was the most frequent cause of discrimination (44%), followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). HWE adversely affected professional activities with colleagues (75%) and patients (53%). Multivariate analysis showed that women (OR: 3.39; 95% confidence interval: 2.97 to 3.86; p < 0.001) and cardiologists early in their career (OR: 1.27; 95% confidence interval: 1.14 to 1.43; p < 0.001) had the highest odds of experiencing HWE.

Conclusions: There is a high global prevalence of HWE in cardiology, including discrimination, emotional harassment, and sexual harassment. HWE has an adverse effect on professional and patient interactions, thus confirming concerns about well-being and optimizing patient care. Institutions and practices should prioritize combating HWE.
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http://dx.doi.org/10.1016/j.jacc.2021.03.301DOI Listing
May 2021

The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19.

Int J Cardiol 2021 May 8. Epub 2021 May 8.

Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Objective: Higher mortality in COVID-19 in men compared to women is recognized, but sex differences in cardiovascular events are less well established. We aimed to determine the independent contribution of sex to stroke, myocardial infarction and death in the setting of COVID-19 infection.

Methods: We performed a retrospective cohort study of hospitalized COVID-19 patients in a racially/ethnically diverse population. Clinical features, laboratory markers and clinical events were initially abstracted from medical records, with subsequent clinician adjudication.

Results: Of 2060 patients, myocardial injury (32% vs 23%, p = 0.019), acute myocardial infarction (2.7% vs 1.6%, p = 0.114), and ischemic stroke (1.8% vs 0.7%, p = 0.007) were more common in men vs women. In-hospital death occurred in 160 men (15%) vs 117 women (12%, p = 0.091). Men had higher odds of myocardial injury (odds ratio (OR) 2.04 [95% CI 1.43-2.91], p < 0.001), myocardial infarction (1.72 [95% CI 0.93-3.20], p = 0.085) and ischemic stroke (2.76 [95% CI 1.29-5.92], p = 0.009). Despite adjustment for demographics and cardiovascular risk factors, male sex predicted mortality (HR 1.33; 95% CI:1.01-1.74; p = 0.041). While men had significantly higher markers of inflammation, in sex-stratified analyses, increase in interleukin-6, C-reactive protein, ferritin and d-dimer were predictive of mortality and myocardial injury similarly in both sexes.

Conclusions: Adjusted odds of myocardial injury, ischemic stroke and all-cause mortality, but not myocardial infarction, are significantly higher in men compared to women with COVID-19. Higher inflammatory markers are present in men but associated similarly with risk in both men and women. These data suggest that adverse cardiovascular outcomes in men vs. women are independent of cardiovascular comorbidities.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106202PMC
May 2021

Understanding the molecular evolution of tiger diversity through DNA barcoding marker ND4 and NADH dehydrogenase complex using computational biology.

Genes Genomics 2021 Jul 21;43(7):759-773. Epub 2021 Apr 21.

Institute For Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, 200704, Republic of Korea.

Background: Currently, Tigers (the top predator of an ecosystem) are on the list of endangered species. Thus the need is to understand the tiger's population genomics to design their conservation strategies.

Objective: We analyzed the molecular evolution of tiger diversity using NADH dehydrogenase subunit 4 (ND4), a significant electron transport chain component.

Methods: We have analyzed nucleotide composition and distribution pattern of ND genes, molecular evolution, evolutionary conservation pattern and conserved blocks of NADH, phylogenomics of ND4, and estimating species divergence, etc., using different bioinformatics tools and software, and MATLAB programming and computing environment.

Results: The nucleotide composition and distribution pattern of ND genes in the tiger genome demonstrated an increase in the number of adenine (A) and a lower trend of A+T content in some place of the distribution analysis. However, the observed distributions were not significant (P > 0.05). Evolutionary conservation analysis showed three highly align blocks (186 to 198, 406 to 416, and 527 to 545). On mapping the molecular evolution of ND4 among model species (n = 30), we observed its presence in a broader range of species. ND4 based molecular evolution of tiger diversity and time divergence for a tiger (20 different other species) shows that genus Panthera originated more or less at a similar time.

Conclusions: The nucleotide composition and nucleotide distribution pattern of tiger ND genes showed the evolutionary pattern and origin of tiger and Panthera lineage concerning the molecular clock, which will help to understand their adaptive evolution.
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http://dx.doi.org/10.1007/s13258-021-01089-wDOI Listing
July 2021

Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study.

J Med Internet Res 2021 05 19;23(5):e25401. Epub 2021 May 19.

Digbi Health, Los Altos, CA, United States.

Background: The COVID-19 pandemic has highlighted the urgency of addressing an epidemic of obesity and associated inflammatory illnesses. Previous studies have demonstrated that interactions between single-nucleotide polymorphisms (SNPs) and lifestyle interventions such as food and exercise may vary metabolic outcomes, contributing to obesity. However, there is a paucity of research relating outcomes from digital therapeutics to the inclusion of genetic data in care interventions.

Objective: This study aims to describe and model the weight loss of participants enrolled in a precision digital weight loss program informed by the machine learning analysis of their data, including genomic data. It was hypothesized that weight loss models would exhibit a better fit when incorporating genomic data versus demographic and engagement variables alone.

Methods: A cohort of 393 participants enrolled in Digbi Health's personalized digital care program for 120 days was analyzed retrospectively. The care protocol used participant data to inform precision coaching by mobile app and personal coach. Linear regression models were fit of weight loss (pounds lost and percentage lost) as a function of demographic and behavioral engagement variables. Genomic-enhanced models were built by adding 197 SNPs from participant genomic data as predictors and refitted using Lasso regression on SNPs for variable selection. Success or failure logistic regression models were also fit with and without genomic data.

Results: Overall, 72.0% (n=283) of the 393 participants in this cohort lost weight, whereas 17.3% (n=68) maintained stable weight. A total of 142 participants lost 5% bodyweight within 120 days. Models described the impact of demographic and clinical factors, behavioral engagement, and genomic risk on weight loss. Incorporating genomic predictors improved the mean squared error of weight loss models (pounds lost and percent) from 70 to 60 and 16 to 13, respectively. The logistic model improved the pseudo R value from 0.193 to 0.285. Gender, engagement, and specific SNPs were significantly associated with weight loss. SNPs within genes involved in metabolic pathways processing food and regulating fat storage were associated with weight loss in this cohort: rs17300539_G (insulin resistance and monounsaturated fat metabolism), rs2016520_C (BMI, waist circumference, and cholesterol metabolism), and rs4074995_A (calcium-potassium transport and serum calcium levels). The models described greater average weight loss for participants with more risk alleles. Notably, coaching for dietary modification was personalized to these genetic risks.

Conclusions: Including genomic information when modeling outcomes of a digital precision weight loss program greatly enhanced the model accuracy. Interpretable weight loss models indicated the efficacy of coaching informed by participants' genomic risk, accompanied by active engagement of participants in their own success. Although large-scale validation is needed, our study preliminarily supports precision dietary interventions for weight loss using genetic risk, with digitally delivered recommendations alongside health coaching to improve intervention efficacy.
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http://dx.doi.org/10.2196/25401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173391PMC
May 2021

Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect.

J Nanobiotechnology 2021 Apr 9;19(1):100. Epub 2021 Apr 9.

Department of Biomedical Science & Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Background: Carvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Thus, this study aims to optimize carvedilol-loaded ethosomes using central composite design, followed by incorporation of synthesized ethosomes into hydrogels for transdermal delivery of carvedilol.

Results: The optimized carvedilol-loaded ethosomes were spherical in shape. The optimized ethosomes had mean particle size of 130 ± 1.72 nm, entrapment efficiency of 99.12 ± 2.96%, cumulative drug release of 97.89 ± 3.7%, zeta potential of - 31 ± 1.8 mV, and polydispersity index of 0.230 ± 0.03. The in-vitro drug release showed sustained release of carvedilol from ethosomes and ethosomal hydrogel. Compared to free carvedilol-loaded hydrogel, the ethosomal gel showed increased penetration of carvedilol through the skin. Moreover, ethosomal hydrogels showed a gradual reduction in blood pressure for 24 h in rats.

Conclusions: Taken together, central composite design can be used for successful optimization of carvedilol-loaded ethosomes formulation, which can serve as the promising transdermal delivery system for carvedilol. Moreover the carvedilol-loaded ethosomal gel can extend the anti-hypertensive effect of carvedilol for a longer time, as compared to free carvedilol, suggesting its therapeutic potential in future clinics.
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http://dx.doi.org/10.1186/s12951-021-00833-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035747PMC
April 2021

Correlations Between Facial Expressivity and Apathy in Elderly People With Neurocognitive Disorders: Exploratory Study.

JMIR Form Res 2021 Mar 31;5(3):e24727. Epub 2021 Mar 31.

Cognition Behaviour Technology Research Unit, Memory Center, Université Côte d'Azur, Nice, France.

Background: Neurocognitive disorders are often accompanied by behavioral symptoms such as anxiety, depression, and/or apathy. These symptoms can occur very early in the disease progression and are often difficult to detect and quantify in nonspecialized clinical settings.

Objective: We focus in this study on apathy, one of the most common and debilitating neuropsychiatric symptoms in neurocognitive disorders. Specifically, we investigated whether facial expressivity extracted through computer vision software correlates with the severity of apathy symptoms in elderly subjects with neurocognitive disorders.

Methods: A total of 63 subjects (38 females and 25 males) with neurocognitive disorder participated in the study. Apathy was assessed using the Apathy Inventory (AI), a scale comprising 3 domains of apathy: loss of interest, loss of initiation, and emotional blunting. The higher the scale score, the more severe the apathy symptoms. Participants were asked to recall a positive and a negative event of their life, while their voice and face were recorded using a tablet device. Action units (AUs), which are basic facial movements, were extracted using OpenFace 2.0. A total of 17 AUs (intensity and presence) for each frame of the video were extracted in both positive and negative storytelling. Average intensity and frequency of AU activation were calculated for each participant in each video. Partial correlations (controlling for the level of depression and cognitive impairment) were performed between these indexes and AI subscales.

Results: Results showed that AU intensity and frequency were negatively correlated with apathy scale scores, in particular with the emotional blunting component. The more severe the apathy symptoms, the less expressivity in specific emotional and nonemotional AUs was displayed from participants while recalling an emotional event. Different AUs showed significant correlations depending on the sex of the participant and the task's valence (positive vs negative story), suggesting the importance of assessing male and female participants independently.

Conclusions: Our study suggests the interest of employing computer vision-based facial analysis to quantify facial expressivity and assess the severity of apathy symptoms in subjects with neurocognitive disorders. This may represent a useful tool for a preliminary apathy assessment in nonspecialized settings and could be used to complement classical clinical scales. Future studies including larger samples should confirm the clinical relevance of this kind of instrument.
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http://dx.doi.org/10.2196/24727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047819PMC
March 2021

Ongoing Clinical Trials of Vaccines to Fight against COVID-19 Pandemic.

Immune Netw 2021 Feb 19;21(1):e5. Epub 2021 Jan 19.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon 24252, Korea.

Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.
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http://dx.doi.org/10.4110/in.2021.21.e5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937508PMC
February 2021

Multimodality Imaging for Cardiac Evaluation in Patients with COVID-19.

Curr Cardiol Rep 2021 03 15;23(5):44. Epub 2021 Mar 15.

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Carnegie 568, Baltimore, MD, 21287, USA.

Purpose Of Review: A growing number of cardiovascular manifestations resulting from the novel SARS-CoV-2 coronavirus (COVID-19) have been described since the beginning of this global pandemic. Acute myocardial injury is common in this population and is associated with higher rates of morbidity and mortality. The focus of this review centers on the recent applications of multimodality imaging in the diagnosis and management of COVID-19-related cardiovascular conditions.

Recent Findings: In addition to standard cardiac imaging techniques such as transthoracic echocardiography, other modalities including computed tomography and cardiac magnetic resonance imaging have emerged as useful adjuncts in select patients with COVID-19 infection, particularly those with suspected ischemic and nonischemic myocardial injury. Data have also emerged suggesting lasting COVID-19 subclinical cardiac effects, which may have long-term prognostic implications. With the spectrum of COVID-19 cardiovascular manifestations observed thus far, it is important for clinicians to recognize the role, strengths, and limitations of multimodality imaging techniques in this patient population.
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http://dx.doi.org/10.1007/s11886-021-01483-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957471PMC
March 2021

Circulating miRNA in atherosclerosis: a clinical biomarker and early diagnostic tool.

Curr Mol Med 2021 Mar 15. Epub 2021 Mar 15.

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Rd, Kolkata, West Bengal 700126. India.

Atherosclerosis, which is a vascular disease, is characterized by narrowing the arteries and forming plaque inside arteries. There is a record 17.5 million associated deaths recorded annually, representing 31% of global death. It has been noted that there is an association between vascular fibrosis and atherosclerosis. The thickening of the arterial wall and reduction of the lumen diameter may cause unwarranted deposition of extracellular matrix (ECM), and these conditions help in the progression of many clinical diseases and pathological conditions such as atherosclerosis. Here, we reviewed the involvement of various circulating microRNAs (miRNAs) in the very early diagnosis of atherosclerosis. We have also tried to provide an insight into the advantages and validation of circulating miRNAs through different techniques. We have discussed different circulating miRNAs, such as miR-17, miR-17-5p, miR-29b, miR-30, miR-92a, miR-126, miR-143, miR-145, miR-146a, miR-212, miR-218, miR-221, miR-222, miR-361-5p, as a biomarker for clinical diagnosis of atherosclerosis. The insightful demonstration in this review will offer a better opportunity for the researchers and technology developers in understanding the current scenario of circulating miRNA, which could facilitate them in improving the current diagnostic technologies of atherosclerosis in clinics.
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http://dx.doi.org/10.2174/1566524021666210315124438DOI Listing
March 2021

The association between coronary graft patency and clinical status in patients with coronary artery disease.

Eur Heart J 2021 04;42(14):1433-1441

Division of Cardiology, NYU Langone Health, 27 W 86th St, New York, NY 10024, USA.

The concept of a direct association between coronary graft patency and clinical status is generally accepted. However, the relationship is more complex and variable than usually thought. Key issues are the lack of a common definition of graft occlusion and of a standardized imaging protocol for patients undergoing coronary bypass surgery. Factors like the type of graft, the timing of the occlusion, and the amount of myocardium at risk, as well as baseline patients' characteristics, modulate the patency-to-clinical status association. Available evidence suggests that graft occlusion is more often associated with non-fatal events rather than death. Also, graft failure due to competitive flow is generally a benign event, while graft occlusion in a graft-dependent circulation is associated with clinical symptoms. In this systematic review, we summarize the evidence on the association between graft status and clinical outcomes.
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http://dx.doi.org/10.1093/eurheartj/ehab096DOI Listing
April 2021

Is Maternal Obesity the Achilles' Heel of Sustainable Efforts to Reduce Adverse Pregnancy Outcomes?

J Am Coll Cardiol 2021 Mar;77(10):1327-1330

Division of Cardiology, Department of Medicine, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.01.023DOI Listing
March 2021

Can We Reduce Premature Mortality Associated With Hypertensive Disorders of Pregnancy?: A Window of Opportunity.

J Am Coll Cardiol 2021 Mar;77(10):1313-1316

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.01.021DOI Listing
March 2021

Disparities in cholesterol screening among a nationally representative sample of pregnant women in the United States.

Eur J Prev Cardiol 2020 Nov 25. Epub 2020 Nov 25.

Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, 6550 Fannin Street, Suite 1801, Houston, TX 77030, USA.

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http://dx.doi.org/10.1093/eurjpc/zwaa100DOI Listing
November 2020

Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice.

J Control Release 2021 Apr 17;332:636-651. Epub 2021 Feb 17.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria 3052, Australia. Electronic address:

The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphatic transport of MPA-related species 83-fold and increased MLN concentrations of MPA >20 fold, when compared to MPA alone, for up to 4 h in mice. At the same time, the plasma exposure of MPA and MPA-TG was similar, limiting the opportunity for systemic side effects. Confocal microscopy and flow cytometry studies with a fluorescent model prodrug (Bodipy-TG) revealed that the prodrug accumulated in the MLN cortex and paracortex at 5 and 10 h following administration and was highly associated with B cells and T cells that are found in these regions of the MLN. Finally, we demonstrated that MPA-TG was significantly more effective than MPA at inhibiting CD4 and CD8 T cell proliferation in the MLN of mice in response to an oral ovalbumin antigen challenge. In contrast, MPA-TG was no more effective than MPA at inhibiting T cell proliferation in peripheral LN when mice were challenged via SC administration of ovalbumin. This paper provides the first evidence of an in vivo pharmacodynamic benefit of targeting the MLN using a TG mimetic prodrug approach. The TG mimetic prodrug technology has the potential to benefit the treatment of a range of conditions where aberrant immune responses are initiated in gut-associated lymphoid tissues.
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http://dx.doi.org/10.1016/j.jconrel.2021.02.008DOI Listing
April 2021

Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF-α and caspase-3 in palmitic acid-induced lipotoxicity in myoblasts.

J Biochem Mol Toxicol 2021 May 18;35(5):e22744. Epub 2021 Feb 18.

School of Studies in Zoology & Biotechnology, Vikram University, Ujjain, Madhya Pradesh, India.

Saturated fatty acids, whose circulating levels are markedly increased in the body, significantly affect the growth and functions of skeletal muscle. These fatty acids may exert a detrimental effect on the undifferentiated skeletal myoblasts that may adversely affect their differentiation. In the present study, the exposure of myoblasts to excess palmitic acid caused an elevation of tumor necrosis factor-α expression and an increase in reactive oxygen species levels consistent with the enhanced inflammation and oxidative stress. Various concentrations of palmitic acid significantly decreased the mitochondrial membrane potential, induced the programmed cell death by an increase in the caspase-3 expression, and DNA fragmentation in the myoblasts. These findings suggest that the increased concentrations of saturated fatty acid in the myoblasts increase lipotoxicity by increasing inflammation and oxidative stress, decreasing the mitochondrial function, and inducing apoptosis.
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http://dx.doi.org/10.1002/jbt.22744DOI Listing
May 2021

Shape recoverable, Au nanoparticles loaded nanocellulose foams as a recyclable catalyst for the dynamic and batch discoloration of dyes.

Carbohydr Polym 2021 Apr 28;258:117693. Epub 2021 Jan 28.

Department of Biomedical Science & Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 24341, Republic of Korea. Electronic address:

An environmental benign in-situ formation and growth of gold nanoparticles (AuNPs) on TEMPO-oxidized cellulose nanofibrils (TOCNF) is reported here. With the active functional groups (aldehyde and carboxyl), TOCNF served as a synchronized reducing and supporting agent for the formation of AuNPs. The entire synthesis process was completed within 30 s under microwave irradiation and regarded as ultra-fast. As obtained [email protected] nanohybrid suspension was freeze-dried to form strong water-activated shape recovery 3D foam. Internal morphology and porosity of the foam were studied by SEM and BET. [email protected] foams exhibited excellent catalytic activity for the discoloration of cationic and anionic dyes in batch and dynamic column processes. The spent foams can be easily recovered and reused up to five cycles with more than 98 % efficiency. During the catalytic processes, no obvious deterioration of the foam structure was observed. Practical applicability of the nanocatalyst was evaluated by treating spiked sea water sample.
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http://dx.doi.org/10.1016/j.carbpol.2021.117693DOI Listing
April 2021

Relationship of Preeclampsia With Maternal Place of Birth and Duration of Residence Among Non-Hispanic Black Women in the United States.

Circ Cardiovasc Qual Outcomes 2021 Feb 10;14(2):e007546. Epub 2021 Feb 10.

Department of Population, Family and Reproductive Health (Y.A.K., X.H., Y.J., A.A.C., X.W.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Background: Preeclampsia is one of the leading causes of maternal mortality in the United States. It disproportionately affects non-Hispanic Black (NHB) women, but little is known about how preeclampsia and other cardiovascular disease risk factors vary among different subpopulations of NHB women in the United States. We investigated the prevalence of preeclampsia by nativity (US born versus foreign born) and duration of US residence among NHB women.

Methods: We analyzed cross-sectional data from the Boston Birth Cohort (1998-2016), with a focus on NHB women. We performed multivariable logistic regression to investigate associations between preeclampsia, nativity, and duration of US residence after controlling for potential confounders.

Results: Of 2697 NHB women, 40.5% were foreign born. Relative to them, US-born NHB women were younger, in higher percentage current smokers, had higher prevalence of obesity (body mass index ≥30 kg/m) and maternal stress, but lower educational level. The age-adjusted prevalence of preeclampsia was 12.4% and 9.1% among US-born and foreign-born women, respectively. When further categorized by duration of US residence, the prevalence of all studied cardiovascular disease risk factors except for diabetes was lower among foreign-born NHB women with <10 versus ≥10 years of US residence. Additionally, the odds of preeclampsia in foreign-born NHB women with duration of US residence <10 years was 37% lower than in US-born NHB women. In contrast, the odds of preeclampsia in foreign-born NHB women with duration of US residence ≥10 years was not significantly different from that of US-born NHB women after adjusting for potential confounders.

Conclusions: The prevalence of preeclampsia and other cardiovascular disease risk factors is lower in foreign-born than in US-born NHB women. The healthy immigrant effect, which typically results in health advantages for foreign-born women, appears to wane with longer duration of US residence (≥10 years). Further research is needed to better understand these associations.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.007546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887058PMC
February 2021

Heart Rate Measurements in Patients with Obstructive Sleep Apnea and Atrial Fibrillation: Prospective Pilot Study Assessing Apple Watch's Agreement With Telemetry Data.

JMIR Cardio 2021 Feb 8;5(1):e18050. Epub 2021 Feb 8.

School of Medicine, Johns Hopkins University, Baltimore, MD, United States.

Background: Patients with obstructive sleep apnea (OSA) are at a higher risk for atrial fibrillation (AF). Consumer wearable heart rate (HR) sensors may be a means for passive HR monitoring in patients with AF.

Objective: The aim of this study was to assess the Apple Watch's agreement with telemetry in measuring HR in patients with OSA in AF.

Methods: Patients with OSA in AF were prospectively recruited prior to cardioversion/ablation procedures. HR was sampled every 10 seconds for 60 seconds using telemetry and an Apple Watch concomitantly. Agreement of Apple Watch with telemetry, which is the current gold-standard device for measuring HR, was assessed using mixed effects limits agreement and Lin's concordance correlation coefficient.

Results: A total of 20 patients (mean 66 [SD 6.5] years, 85% [n=17] male) participated in this study, yielding 134 HR observations per device. Modified Bland-Altman plot revealed that the variability of the paired difference of the Apple Watch compared with telemetry increased as the magnitude of HR measurements increased. The Apple Watch produced regression-based 95% limits of agreement of 27.8 - 0.3 × average HR - 15.0 to 27.8 - 0.3 × average HR + 15.0 beats per minute (bpm) with a mean bias of 27.8 - 0.33 × average HR bpm. Lin's concordance correlation coefficient was 0.88 (95% CI 0.85-0.91), suggesting acceptable agreement between the Apple Watch and telemetry.

Conclusions: In patients with OSA in AF, the Apple Watch provided acceptable agreement with HR measurements by telemetry. Further studies with larger sample populations and wider range of HR are needed to confirm these findings.
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http://dx.doi.org/10.2196/18050DOI Listing
February 2021

Immunoinformatics Approach for the Identification and Characterization of T Cell and B Cell Epitopes towards the Peptide-Based Vaccine against SARS-CoV-2.

Arch Med Res 2021 05 29;52(4):362-370. Epub 2021 Jan 29.

Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252,Gangwon-do, Republic of Korea. Electronic address:

Presently, immunoinformatics is playing a significant role in epitope identification and vaccine designing for various critical diseases. Using immunoinformatics, several scientists are trying to identify and characterize T cell and B cell epitopes as well as design peptide-based vaccine against SARS-CoV-2. In this review article, we have tried to discuss the importance in adaptive immunity and its significance for designing the SARS-CoV-2 vaccine. Moreover, we have attempted to illustrate several significant key points for utilizing immunoinformatics for vaccine designing, such as the criteria for selection and identification of epitopes, T cell epitope, and B cell epitope prediction and different emerging tools/databases for immunoinformatics. In the current scenario, a few immunoinformatics studies have been performed for various infectious pathogens and related diseases. Thus, we have also summarized and included these current immunoinformatics studies in this review article. Finally, we have discussed about the probable T cell and B cell epitopes and their identification and characterization for vaccine designing against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.arcmed.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846223PMC
May 2021

SARS-CoV-2 and other human coronaviruses: Mapping of protease recognition sites, antigenic variation of spike protein and their grouping through molecular phylogenetics.

Infect Genet Evol 2021 04 23;89:104729. Epub 2021 Jan 23.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252, Gangwon-do, Republic of Korea. Electronic address:

In recent years, a total of seven human pathogenic coronaviruses (HCoVs) strains were identified, i.e., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Here, we performed an analysis of the protease recognition sites and antigenic variation of the S-protein of these HCoVs. We showed tissue-specific expression pattern, functions, and a number of recognition sites of proteases in S-proteins from seven strains of HCoVs. In the case of SARS-CoV-2, we found two new protease recognition sites, each of calpain-2, pepsin-A, and caspase-8, and one new protease recognition site each of caspase-6, caspase-3, and furin. Our antigenic mapping study of the S-protein of these HCoVs showed that the SARS-CoV-2 virus strain has the most potent antigenic epitopes (highest antigenicity score with maximum numbers of epitope regions). Additionally, the other six strains of HCoVs show common antigenic epitopes (both B-cell and T-cell), with low antigenicity scores compared to SARS-CoV-2. We suggest that the molecular evolution of structural proteins of human CoV can be classified, such as (i) HCoV-NL63 and HCoV-229E, (ii) SARS-CoV-2, and SARS-CoV and (iii) HCoV-OC43 and HCoV-HKU1. In conclusion, we can presume that our study might help to prepare the interventions for the possible HCoVs outbreaks in the future.
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http://dx.doi.org/10.1016/j.meegid.2021.104729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826164PMC
April 2021

A Novel Multi-Epitopic Peptide Vaccine Candidate Against : In-Silico Identification, Design, Cloning and Validation Through Molecular Dynamics.

Int J Pept Res Ther 2021 Jan 20:1-18. Epub 2021 Jan 20.

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Rd, Kolkata, West Bengal 700126 India.

is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein-protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (- 151.4, + / - 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites.

Supplementary Information: The online version of this article (10.1007/s10989-020-10157-w) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s10989-020-10157-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816556PMC
January 2021

Therapeutic advances of miRNAs: A preclinical and clinical update.

J Adv Res 2021 Feb 29;28:127-138. Epub 2020 Aug 29.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon-Do 24252, Republic of Korea.

miRNAs, a class of small endogenous RNAs, are one of the essential biopharmaceuticals which are in commercial spans as next-generation medicine in recent times. A snapshot of the current scenario regarding the miRNAs as biopharmaceuticals have been discussed. In this work, biopharmaceutical companies working with miRNAs and the current status of preclinical/clinical trials about miRNA therapeutics have been reviewed. Finally, recent updates on the absorption, distribution, metabolism, and excretion (ADME), as well as a delivery system of miRNAs, have been illustrated.
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http://dx.doi.org/10.1016/j.jare.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753224PMC
February 2021

Glutathione peroxidase-1 and neuromodulation: Novel potentials of an old enzyme.

Food Chem Toxicol 2021 Feb 29;148:111945. Epub 2020 Dec 29.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

Glutathione peroxidase (GPx) acts in co-ordination with other signaling molecules to exert its own antioxidant role. We have demonstrated the protective effects of GPx,/GPx-1, a selenium-dependent enzyme, on various neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, cerebral ischemia, and convulsive disorders). In addition, we summarized the recent findings indicating that GPx-1 might play a role as a neuromodulator in neuropsychiatric conditions, such as, stress, bipolar disorder, schizophrenia, and drug intoxication. In this review, we attempted to highlight the mechanistic scenarios mediated by the GPx/GPx-1 gene in impacting these neurodegenerative and neuropsychiatric disorders, and hope to provide new insights on the therapeutic interventions against these disorders.
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http://dx.doi.org/10.1016/j.fct.2020.111945DOI Listing
February 2021

Sex-based differences in revascularization and 30-day readmission after ST-segment-elevation myocardial infarction in the United States.

Cardiovasc Revasc Med 2020 Dec 17. Epub 2020 Dec 17.

Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, 1305 York Ave, 8(th) Floor, New York, NY 10021, United States of America; Weill Cornell Cardiovascular Outcomes Research Group (CORG), Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, 1305 York Ave, 8(th) Floor - Cardiology, New York, NY 10021, United States of America; Weill Cornell Women's Heart Program, Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, 1305 York Ave, 8th Floor - Cardiology, New York, NY 10021, United States of America.

Background: Cardiovascular disease is the leading cause of death for women in the United States. Revascularization is considered the standard of care for treatment of ST-segment elevation myocardial infarction (STEMI) and is known to reduce readmission. However there is a paucity of data that examines the sex-dependent impact of revascularization on readmission. We aimed to investigate sex differences in revascularization rates, 30-day readmission rates, and primary cause of readmissions following STEMIs.

Methods: STEMI hospitalizations were selected in the Nationwide Readmissions Database from 2010 to 2014. Revascularization rates, 30-day readmission rates, and primary cause of readmission were examined. Interaction between sex and revascularization was assessed. Multivariable regression analysis was performed to identify predictors of 30-day readmission and revascularization for both sexes.

Results: 219,944 women and 489,605 men were admitted with STEMIs. Women were more likely to be older, and have more comorbidities. Women were less likely to undergo revascularization by percutaneous coronary intervention (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.66-0.70) or coronary artery bypass graft surgery (adjusted OR 0.40; CI 0.39-0.44). Women had higher 30-day readmission rates (15.7% vs. 10.8%, p < 0.001; OR 1.20, CI 1.17-1.23), and revascularization in women was not associated with a decreased likelihood of 30-day readmission. The primary cardiac cause of readmission in women was heart failure.

Conclusion: Compared to men, women with STEMIs had lower rates of revascularization and higher rates of 30-day readmission. When revascularized, women were still more likely to be readmitted as compared to non-revascularized women.
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http://dx.doi.org/10.1016/j.carrev.2020.12.016DOI Listing
December 2020

Probiotics-derived metabolite ameliorates skin allergy by promoting differentiation of FOXP3 regulatory T cells.

J Allergy Clin Immunol 2021 Apr 14;147(4):1517-1521. Epub 2020 Dec 14.

Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.11.040DOI Listing
April 2021