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1.
ASAIO J ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38905611

ABSTRACT

Right ventricular (RV) dysfunction (RVD) after orthotopic heart transplantation (OHT) is a common cause of morbidity and mortality. Impella RP Flex was recently approved for RV support as a temporary mechanical circulatory device. We present the first case of its use in managing RVD in a patient after OHT. Here, a 40 year old male patient with familial dilated cardiomyopathy and factor V Leiden mutation presented with Society for Cardiovascular Angiography & Interventions (SCAI) stage B cardiogenic shock. Hemodynamics at admission were indicative of need for intra-aortic balloon pump (IABP) support. Hemodynamics improved and patient underwent OHT. Postoperative day (POD) 1, IABP support was changed to 1:2 and eventually removed. Hemodynamics deteriorated quickly, requiring pharmacologic RV support and diuresis, but refractory RV failure persisted. Impella RP Flex was chosen due to the patient's small size and was placed via the right internal jugular vein on POD 12. The procedure was well tolerated, with the patient ambulatory the following day (POD 13). Impella was removed on POD 25 after 13 days of support. Patient achieved normal kidney, intrinsic rhythm improved sinus rhythm, and ultimately discharged on POD 50. Impella RP flex has emerged as a promising future indication as single or biventricular support postcardiac transplantation.

4.
Cardiovasc Res ; 120(6): 630-643, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38230606

ABSTRACT

AIMS: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation. METHODS AND RESULTS: KDM5A, B, and C proteins were mainly expressed in the early post-natal stages, and their expressions were progressively downregulated in the post-natal CMs and were absent in adult hearts and CMs. In contrast, KDM5 proteins were persistently expressed in the iPSC-CMs up to 60 days after the induction of myogenic differentiation, consistent with the immaturity of these cells. Inhibition of KDM5 by KDM5-C70 -a pan-KDM5 inhibitor, induced differential expression of 2372 genes, including upregulation of genes involved in fatty acid oxidation (FAO), OXPHOS, and myogenesis in the iPSC-CMs. Likewise, genome-wide profiling of H3K4me3 binding sites by the cleavage under targets and release using nuclease assay showed enriched of the H3K4me3 peaks at the promoter regions of genes encoding FAO, OXPHOS, and sarcomere proteins. Consistent with the chromatin and gene expression data, KDM5 inhibition increased the expression of multiple sarcomere proteins and enhanced myofibrillar organization. Furthermore, inhibition of KDM5 increased H3K4me3 deposits at the promoter region of the ESRRA gene and increased its RNA and protein levels. Knockdown of ESRRA in KDM5-C70-treated iPSC-CM suppressed expression of a subset of the KDM5 targets. In conjunction with changes in gene expression, KDM5 inhibition increased oxygen consumption rate and contractility in iPSC-CMs. CONCLUSION: KDM5 inhibition enhances maturation of iPSC-CMs by epigenetically upregulating the expressions of OXPHOS, FAO, and sarcomere genes and enhancing myofibril organization and mitochondrial function.


Subject(s)
Cell Differentiation , Fatty Acids , Myocytes, Cardiac , Myofibrils , Oxidative Phosphorylation , Retinoblastoma-Binding Protein 2 , Humans , Cells, Cultured , Fatty Acids/metabolism , Gene Expression Regulation, Developmental , Histones/metabolism , Histones/genetics , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/enzymology , Mitochondria, Heart/enzymology , Mitochondria, Heart/metabolism , Mitochondria, Heart/genetics , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/metabolism , Myofibrils/metabolism , Myofibrils/enzymology , Oxidation-Reduction , Promoter Regions, Genetic , Retinoblastoma-Binding Protein 2/metabolism , Retinoblastoma-Binding Protein 2/genetics
5.
bioRxiv ; 2023 May 28.
Article in English | MEDLINE | ID: mdl-37090524

ABSTRACT

Rationale: Human pluripotent stem cell-derived CMs (iPSC-CMs) are a valuable tool for disease modeling, cell therapy and to reconstruct the CM maturation process and identify, characterize factors that regulate maturation. The transition from immature fetal to adult CM entails coordinated regulation of the mature gene programming, which is characterized by the induction of myofilament and OXPHOS gene expression among others. Recent studies in Drosophila , C. elegans, and C2C12 myoblast cell lines have implicated the histone H3K4me3 demethylase KDM5 and its homologs, as a potential regulator of developmental gene program and mitochondrial function. We speculated that KDM5 may potentiate the maturation of iPSC-CMs by targeting a conserved epigenetic program that encompass mitochondrial OXPHOS and other CM specific maturation genes. Objectives: The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation. Methods and Results: Immunoblot analysis revealed that KDM5A, B, and C expression was progressively downregulated in postnatal cardiomyocytes and absent in adult hearts and CMs. Additionally, KDM5 proteins were found to be persistently expressed in iPSC-CMs up to 60 days after the onset of myogenic differentiation, consistent with the immaturity of these cells. Inhibition of KDM5 by KDM5-C70 -a pan-KDM5 inhibitor-resulted in differential regulation of 2,372 genes including upregulation of Fatty acid oxidation (FAO), OXPHOS, and myogenic gene programs in iPSC-CMs. Likewise, genome-wide profiling of H3K4me3 binding sites by the CUT&RUN assay revealed enriched H3K4me3 peaks at the promoter regions of FAO, OXPHOS, and sarcomere genes. Consistent with the chromatin and gene expression data, KDM5 inhibition led to increased expression of multiple sarcomere proteins, enhanced myofibrillar organization and improved calcium handling. Furthermore, inhibition of KDM5 increased H3K4me3 deposits at the promoter region of the ESRRA gene, which is known to regulate OXPHOS and cardiomyocyte maturation, and resulted in its increased RNA and protein levels. Finally, KDM5 inhibition increased baseline, peak, and spare oxygen consumption rates in iPSC-CMs. Conclusions: KDM5 regulates the maturation of iPSC-CMs by epigenetically regulating the expression of ESRRA, OXPHOS, FAO, and sarcomere genes and enhancing myofibril organization and mitochondrial function.

6.
Neurology ; 101(3): e336-e342, 2023 07 18.
Article in English | MEDLINE | ID: mdl-36859406

ABSTRACT

We report the case of a middle-aged man who presented with acute painless monocular vision loss. His medical history was remarkable for chronic total occlusion of the ipsilateral internal carotid artery (ICA) and a recent carotid endarterectomy (CEA) on the contralateral ICA. In a stepwise multidisciplinary approach assessment, we review the differential diagnosis of acute vision loss and investigate how the patient's intracranial and extracranial hemodynamic reorganization after chronic ICA occlusion may affect the clinical reasoning. Early complications of CEA and the differential diagnosis of new-onset anisocoria are also discussed.


Subject(s)
Carotid Artery Diseases , Carotid Stenosis , Endarterectomy, Carotid , Male , Middle Aged , Humans , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Carotid Artery, Internal/diagnostic imaging , Vision, Monocular , Carotid Artery Diseases/complications , Clinical Reasoning
7.
Environ Sci Pollut Res Int ; 30(10): 24987-25012, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35781666

ABSTRACT

The depletion of fossil fuels coupled with stringent environmental laws has encouraged us to develop sustainable renewable energy. Due to its numerous benefits, anaerobic digestion (AD) has emerged as an environment-friendly technology. Biogas generated during AD is primarily a mixture of CH4 (65-70%) and CO2 (20-25%) and a potent energy source that can combat the energy crisis in today's world. Here, an attempt has been made to provide a broad understanding of AD and delineate the effect of various operational parameters influencing AD. The characteristics of fruit and vegetable waste (FVW) and its feasibility as a potent substrate for AD have been studied. This review also covers traditional challenges in managing FVW via AD, the implementation of various bioreactor systems to manage large amounts of organic waste and their operational boundaries, microbial consortia involved in each phase of digestion, and various strategies to increase biogas production.


Subject(s)
Fruit , Vegetables , Anaerobiosis , Biofuels , Bioreactors , Methane
9.
Diagnostics (Basel) ; 12(12)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36553105

ABSTRACT

Rhino-orbital cerebral mucor mycosis is a rare disease entity, where retinal involvement is described in the literature mostly as CRAO. However, pathological studies have shown mucor invading the choroid and retina with a neutrophilic reaction. So, it is pertinent that retinal inflammation secondary to invading mucor has some role in microstructural changes seen in the vitreous and retina of these patients. This novel study aims to describe the vitreal and retinal features of patients with vision-threatening rhino-orbital cerebral mucor mycosis and how they evolve on spectral domain optical coherence tomography (SD-OCT). This study shall also provide insight into the pathophysiology of these vitreoretinal manifestations by in vitro analysis of the exenterated orbital content. Fifteen eyes of fifteen patients with vision-threatening ROCM treated with standard care were enrolled in this study and underwent complete ophthalmic examination, serial colour fundus photography, and SD-OCT for both qualitative and quantitative analysis, at baseline and follow-up visits. SD-OCT on serial follow-up revealed thickening and increased inner-retinal reflectivity at presentation followed by thinning of both, other features such as the loss of the inner-retinal organized layer structure, external limiting membrane (ELM) disruption, necrotic spaces in the outer retina, and hyperreflective foci. Vitreous cells with vitreous haze were also seen. There was a significant reduction in CMT, inner and outer retinal thickness, total retinal thickness (all p < 0.05) with time, the quantum of reduction concentrated primarily to the inner retina. In summary, in vivo and in vitro analysis revealed that early microstructural changes were primarily a result of retinal infarctions secondary to thrombotic angioinvasion. With the late microstructural changes, there was possible sequelae of retinal infarction with some contribution from the inflammation, resulting from mucor invading the choroid and retina.

10.
Transfus Apher Sci ; 61(6): 103455, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35618641

ABSTRACT

INTRODUCTION: The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. METHODS: This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. RESULTS: Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. CONCLUSIONS: We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved.


Subject(s)
COVID-19 , Humans , COVID-19/mortality , COVID-19/therapy , COVID-19 Serotherapy , Immunization, Passive/methods , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
11.
J Am Heart Assoc ; 11(8): e024229, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35435011

ABSTRACT

Background Team-based models of cardio-obstetrics care have been developed to address the increasing rate of maternal mortality from cardiovascular diseases. Cardiovascular clinician and trainee knowledge and comfort with this topic, and the extent of implementation of an interdisciplinary approach to cardio-obstetrics, are unknown. Methods and Results We aimed to assess the current state of cardio-obstetrics knowledge, practices, and services provided by US cardiovascular clinicians and trainees. A survey developed in conjunction with the American College of Cardiology was circulated to a representative sample of cardiologists (N=311), cardiovascular team members (N=51), and fellows in training (N=139) from June 18, 2020, to July 29, 2020. Knowledge and attitudes about the provision of cardiovascular care to pregnant patients and the prevalence and composition of cardio-obstetrics teams were assessed. The widest knowledge gaps on the care of pregnant compared with nonpregnant patients were reported for medication safety (42%), acute coronary syndromes (39%), aortopathies (40%), and valvular heart disease (30%). Most respondents (76%) lack access to a dedicated cardio-obstetrics team, and only 29% of practicing cardiologists received cardio-obstetrics didactics during training. One third of fellows in training reported seeing pregnant women 0 to 1 time per year, and 12% of fellows in training report formal training in cardio-obstetrics. Conclusions Formalized training in cardio-obstetrics is uncommon, and limited access to multidisciplinary cardio-obstetrics teams and large knowledge gaps exist among cardiovascular clinicians. Augmentation of cardio-obstetrics education across career stages is needed to reduce these deficits. These survey results are an initial step toward developing a standard expectation for clinicians' training in cardio-obstetrics.


Subject(s)
Cardiologists , Cardiology , Cardiovascular Diseases , Obstetrics , Cardiology/education , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Female , Humans , Maternal Mortality , Pregnancy , United States
12.
Langmuir ; 38(15): 4567-4577, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35394793

ABSTRACT

Aerosols and microdroplets are known to act as carriers for pathogens or vessels for chemical reactions. The natural occurrence of evaporation of these droplets has implications for the viability of pathogens or chemical processes. For example, it is important to understand how pathogens survive extreme physiochemical conditions such as confinement and osmotic stress induced by evaporation of aerosol droplets. Previously, larger evaporating droplets were proposed as model systems as the processes in the tiny aerosol droplets are difficult to image. In this context, we propose the concept of evaporation of capillary-clustered aqueous microdroplets dispersed in a thin oil layer. The configuration produces spatially segregated evaporation rates. It allows comparing the consequences of evaporation and its rate for processes occurring in droplets. As a proof of concept, we study the consequences of evaporation and its rate using Escherichia coli (E. coli) and Bacillus subtilis as model organisms. Our experiments indicate that the rate of evaporation of microdroplets is an important parameter in deciding the viability of contained microorganisms. With slow evaporation, E. coli could mitigate the osmotic stress by K+ ion uptake. Our method may also be applicable to other evaporating droplet systems, for example, microdroplet chemistry to understand the implications of evaporation rates.


Subject(s)
Escherichia coli , Microfluidics , Aerosols/chemistry , Water/chemistry
13.
IUBMB Life ; 74(1): 101-116, 2022 01.
Article in English | MEDLINE | ID: mdl-34455667

ABSTRACT

High altitude is an environmental stress that is accompanied with numerous adverse biological responses, including skeletal muscle weakness and muscle protein loss. Skeletal muscle wasting is an important clinical problem, progressing to critical illness, associated with increased morbidity and mortality. The present study explores the protective efficacy of endogenous dipeptide, carnosine (CAR), supplementation in ameliorating skeletal muscle protein loss under hypobaric hypoxia (HH). Male Sprague-Dawley rats (n = 5) were randomly divided into control group, HH-exposed group (3 days HH exposure equivalent to 7,620 m), and HH-exposed rats supplemented with carnosine (3 days; 150 mg/kg b.w, orally) (HH + CAR). HH-exposed rats supplemented with CAR ameliorated HH-induced oxidative protein damage, lipid peroxidation, and maintained pro-inflammatory cytokines levels. HH-associated muscle protein degradative pathways, including calpain, ubiquitination, endoplasmic reticulum stress, autophagy, and apoptosis were also regulated in carnosine-supplemented rats. Further, the muscle damage marker, the levels of serum creatine phosphokinase were also reduced in HH + CAR co-supplemented rats which proved the protective efficacy of CAR against hypobaric hypoxia-induced muscle protein loss. Altogether, CAR supplementation ameliorated HH-induced skeletal muscle protein loss via performing multifaceted ways, mainly by maintaining redox homeostasis and proteostasis in skeletal muscle.


Subject(s)
Carnosine , Proteostasis , Animals , Carnosine/metabolism , Carnosine/pharmacology , Dietary Supplements , Dipeptides/metabolism , Endoplasmic Reticulum Stress , Hypoxia/drug therapy , Hypoxia/metabolism , Male , Muscle, Skeletal/metabolism , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley
14.
Asian J Psychiatr ; 66: 102880, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34688015

ABSTRACT

While higher anxiety during antenatal period cause several maternal and foetal health related complications, lower anxiety levels are found to be associated with lesser "precautionary behaviours" and consequently greater risk of infection, during the COVID-19 pandemic. In this study, we aimed to assess rates and determinants of generalized anxiety at the time of the pandemic as well as anxiety that was specific to the context of being pregnant during the COVID-19 pandemic. (COVID-19-antenatal anxiety) in Indian women. This hospital-based, cross-sectional study using face-to-face interviews was conducted at antenatal clinics of five medical college hospitals in India. The Generalized Anxiety Disorder-7 scale (GAD -7) and a customized scale to assess antenatal COVID-19 anxiety along with other tools that assessed social support and COVID-19-risk perception were administered to 620 pregnant women. We found that the percentage of women with moderate or severe anxiety based on GAD -7 was 11.1%. Multivariate analysis showed that higher COVID-19-risk perception, greater antenatal COVID-19 anxiety and lower perceived support significantly predicted moderate and severe generalized anxiety. Greater number of weeks of gestation, lower education, semiurban habitat and lower perceived social support were significant predictors of antenatal COVID-19 anxiety. We conclude that the rates of anxiety in pregnant women though not very high, still warrant attention and specific interventions.


Subject(s)
COVID-19 , Pregnant Women , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Cross-Sectional Studies , Depression , Female , Humans , India/epidemiology , Pandemics , Pregnancy , SARS-CoV-2
15.
ESC Heart Fail ; 8(3): 2349-2353, 2021 06.
Article in English | MEDLINE | ID: mdl-33787080

ABSTRACT

AIMS: Outflow graft obstruction is a poorly described complication following left ventricular assist device (LVAD) surgery. We sought to define the incidence of LVAD outflow graft obstruction and assess clinical outcomes with a percutaneous treatment strategy. METHODS AND RESULTS: From January 2012 to October 2020, 322 patients with LVAD were managed at our institution. Patients with LVAD outflow graft obstruction were identified by cardiac computed tomography with angiography and invasive haemodynamic assessment and were subsequently treated with percutaneous intervention. Poisson regression was used to analyse time-dependent differences in the incidence of LVAD outflow graft obstruction. Kaplan-Meier analysis was used to estimate survival. Twenty patients (6.2%) developed haemodynamically significant LVAD outflow graft obstruction at a rate of 0.03 events per patient-year. Outflow graft obstruction presented a median of 33 (26-49) months after surgery. Patients presented with low estimated LVAD pump flow (95%), heart failure (90%), or both (85%), and 59% developed cardiogenic shock prior to intervention. The most common aetiology identified by cardiac computed tomography with angiography was external compression of the outflow graft (78%). On presentation, the median peak gradient in the outflow graft was 78 (64-100) mmHg. Outflow graft stenting was 100% successful with no in-hospital mortality, and it reduced the peak outflow graft gradient to 10 (2-17) mmHg (P < 0.001). Outflow graft stenting was durable with two patients (10%) requiring a repeat procedure over a median follow-up of 13 (7-20) months and did not impact survival. CONCLUSIONS: Left ventricular assist device outflow graft obstruction is a relatively common and underappreciated cause of recurrent heart failure and LVAD dysfunction. Outflow graft stenting can be achieved with low morbidity and provides a long-term solution to this complication.


Subject(s)
Heart Failure , Heart-Assist Devices , Heart-Assist Devices/adverse effects , Hospital Mortality , Humans , Retrospective Studies , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/etiology
16.
IUBMB Life ; 73(2): 375-389, 2021 02.
Article in English | MEDLINE | ID: mdl-33368975

ABSTRACT

Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)-induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH-induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH-induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro-inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti-inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway-related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH-induced skeletal muscle damage and protein loss.


Subject(s)
Gene Expression Regulation/drug effects , Hypoxia/physiopathology , Inflammation/drug therapy , Muscle Proteins/metabolism , Muscle, Skeletal/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Disease Models, Animal , Inflammation/metabolism , Inflammation/pathology , Male , Muscle Proteins/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Oxidation-Reduction , Oxidative Stress , Proto-Oncogene Proteins c-akt/genetics , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Up-Regulation , Ursolic Acid
17.
Free Radic Biol Med ; 160: 643-656, 2020 11 20.
Article in English | MEDLINE | ID: mdl-32916280

ABSTRACT

At extreme altitude, prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy. Hypobaric hypoxia altered redox homeostasis and impaired calcium ion handling in skeletal muscles. Dysregulated Ca2+ homeostasis and activated calpain is the prime stressor in high altitude hypoxia while the reason for subsequent abnormal release of pathological Ca2+ into cytoplasm is largely unexplored. The present study identified the redox remodeling in the Ca2+ release channel, Ryanodine Receptor (RyR1) owing to its hypernitrosylation state in skeletal muscles in chronic hypobaric hypoxia exposed rats. RyR1-hypernitrosylation decreases the binding of FKBP12/calstabin-1 and other complexes from the channel, causing "leakiness" in RyR1 ion-channel. A strong RyR1 stabilizer, S107 enhanced binding affinity of FKBP12 with hypernitrosylated RyR1, reduced Sarco(endo)plasmic reticulum (SR) Ca2+ leak and improved muscle strength and function under chronic hypoxia. Administration of S107 inhibited the skeletal muscle damage, maintained ultrastructure of sarcomere and sarcolemmal integrity. Histological analysis proved the increase in cross-sectional area of myofibers. Further, the number of apoptotic cells was also reduced by S107 treatment. Conclusively, we proposed that the redox remodeling of RyR1 (hypernitrosylated-RyR1) might be responsible for dysregulated Ca2+ homeostasis which consequently impaired muscle strength and function in response to chronic hypoxic stress. Reduced SR Ca2+ leak and enhanced binding affinity of FKBP12 may provide a novel therapeutic avenue in ameliorating skeletal muscle atrophy at high altitude.


Subject(s)
Altitude , Ryanodine Receptor Calcium Release Channel , Animals , Calcium/metabolism , Homeostasis , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Oxidation-Reduction , Rats , Ryanodine Receptor Calcium Release Channel/metabolism , Sarcoplasmic Reticulum/metabolism
18.
Curr Hypertens Rep ; 22(9): 64, 2020 08 27.
Article in English | MEDLINE | ID: mdl-32852628

ABSTRACT

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy affect about 5-10% of pregnancies impacting maternal, fetal, and neonatal outcomes. We review the recent studies in this field and discuss the pathophysiology, diagnosis, and management of hypertension during pregnancy, as well as the short- and long-term consequences on the cardiovascular health of women. RECENT FINDINGS: Although the American College of Cardiology/American Heart Association revised their guidelines for hypertension in the general population in 2017, hypertension during pregnancy continues to be defined as a systolic blood pressure (SBP) ≥ 140 mmHg and/or a diastolic blood pressure (DBP) ≥ 90 mmHg, measured on two separate occasions. The addition of stage 1 hypertension will increase the prevalence of hypertension during pregnancy, identifying more women at risk of preeclampsia; however, more research is needed before changing the BP goal because a lower target BP has a risk of poor placental perfusion. Women with chronic hypertension have a higher incidence of superimposed preeclampsia, cesarean section, preterm delivery before 37 weeks' gestation, birth weight less than 2500 g, neonatal unit admission, and perinatal death. They also have a higher risk of developing cardiovascular disease later in life. The guidelines recommend low-dose aspirin for women with moderate and high risk of preeclampsia. While treating pregnant women with hypertension, the effectiveness of the antihypertensive agent must be balanced with risks to the fetus. Hypertensive disorders of pregnancy should be appropriately and promptly recognized and treated during pregnancy. They should further be co-managed by the obstetrician and cardiologist to decrease the long-term negative impact on the cardiovascular health of women.


Subject(s)
Hypertension , Pre-Eclampsia , Pregnancy Complications, Cardiovascular , Aspirin , Cesarean Section , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Infant, Newborn , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/drug therapy , Pregnancy Complications, Cardiovascular/epidemiology
19.
Rev Cardiovasc Med ; 21(1): 123-127, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32259911

ABSTRACT

Infective endocarditis (IE) is a life threatening disease requiring lengthy hospitalizations, complex multidisciplinary management and high health care costs. In this study, we analyzed the National Readmissions' Database (NRD) to identify infective endocarditis cases and the causative organisms, clinical determinants, length of stay, in-hospital mortality, and 30-day hospital readmission rates. The study cohort was derived from Healthcare Cost and Utilization Project's National Readmission Database between 2010-15. We queried the National Readmissions' Database using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic code for infective endocarditis (421.0) and identified a total of 187,438 index admissions. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for statistical analyses. A total of 187,438 patients with a primary diagnosis of IE were identified over 6 years (2010-2015). Twenty-four percent (44,151 patients) were readmitted within 30 days. Most common etiologies for readmission included sepsis (14%), acute heart failure (8%), acute kidney injury (6%), intracardiac device infection (5.6%) and recurrence of IE (2.7%). Predictors of increased readmissions included female sex, staphylococcus aureus infection, diabetes, chronic lung disease, chronic liver disease, acute kidney injury, acute heart failure and anemia. In-hospital mortality for the readmission of IE was 13%, and average length of stay during the re-admission was 12 days. IE is associated with high rates of index admission mortality and for 30-day readmissions of which are associated with a substantial risk of death.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cardiac Surgical Procedures , Endocarditis/therapy , Patient Readmission , Anti-Bacterial Agents/adverse effects , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/mortality , Comorbidity , Databases, Factual , Endocarditis/diagnosis , Endocarditis/microbiology , Endocarditis/mortality , Female , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , United States
20.
JACC Case Rep ; 2(1): 101-106, 2020 Jan.
Article in English | MEDLINE | ID: mdl-34316974

ABSTRACT

Cardiac involvement in sarcoidosis is an uncommon manifestation of the disease process. Diagnosis and treatment during pregnancy can be challenging due to life-threatening ventricular arrhythmias. We describe a case of a 43-year-old, 21-week pregnant woman who presented after 2 episodes of syncope and was diagnosed with presumed cardiac sarcoidosis. (Level of Difficulty: Beginner.).

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