Estrogen has pleiotropic effects on the cardiovascular system. The mechanisms by which estrogen confers these pleiotropic effects are undergoing active investigation. Until a decade ago, all estrogen ...signaling was thought to occur by estrogen binding to nuclear estrogen receptors (estrogen receptor-α and estrogen receptor-β), which bind to DNA and function as ligand-activated transcription factors. Estrogen binding to the receptor alters gene expression, thereby altering cell function. Estrogen also binds to nuclear estrogen receptors that are tethered to the plasma membrane, resulting in acute activation of signaling kinases such as PI3K. An orphan G-protein-coupled receptor, G-protein-coupled receptor 30, can also bind estrogen and activate acute signaling pathways. Thus, estrogen can alter cell function by binding to different estrogen receptors. This article reviews the different estrogen receptors and their signaling mechanisms, discusses mechanisms that regulate estrogen receptor levels and locations, and considers the cardiovascular effects of estrogen signaling.
Estrogen has important effects on cardiovascular function including regulation of vascular function, blood pressure, endothelial relaxation, and the development of hypertrophy and cardioprotection. ...However, the mechanisms by which estrogen mediates these effects are still poorly understood. As detailed in this review, estrogen can regulate transcription by binding to 2 nuclear receptors, ERα and ERβ, which differentially regulate gene transcription. ERα and ERβ regulation of gene transcription is further modulated by tissue-specific coactivators and corepressors. Estrogen can bind to ERα and ERβ localized at the plasma membrane as well as G-protein-coupled estrogen receptor to initiate membrane delimited signaling, which enhances kinase signaling pathways that can have acute and long-term effects. The kinase signaling pathways can also mediate transcriptional changes and can synergize with the ER to regulate cell function. This review will summarize the beneficial effects of estrogen in protecting the cardiovascular system through ER-dependent mechanisms with an emphasis on the role of the recently described ER membrane signaling mechanisms.
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda; and Johns Hopkins Medical Institute, Baltimore, ...Maryland
Mitochondria play an important role in cell death and cardioprotection. During ischemia, when ATP is progressively depleted, ion pumps cannot function resulting in a rise in calcium (Ca 2+ ), which further accelerates ATP depletion. The rise in Ca 2+ during ischemia and reperfusion leads to mitochondrial Ca 2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen allows generation of ATP; however, damage to the electron transport chain results in increased mitochondrial generation of reactive oxygen species (ROS). Mitochondrial Ca 2+ overload and increased ROS can result in opening of the mitochondrial permeability transition pore, which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis result in rupture of the plasma membrane and cell death. Mitochondria have long been proposed as central players in cell death, since the mitochondria are central to synthesis of both ATP and ROS and since mitochondrial and cytosolic Ca 2+ overload are key components of cell death. Many cardioprotective mechanisms converge on the mitochondria to reduce cell death. Reducing Ca 2+ overload and reducing ROS have both been reported to reduce ischemic injury. Preconditioning activates a number of signaling pathways that reduce Ca 2+ overload and reduce activation of the mitochondrial permeability transition pore. The mitochondrial targets of cardioprotective signals are discussed in detail.
Cyclophilin D (CypD) is a mitochondrial peptidyl-prolyl cis-trans isomerase, well-known for regulating the mitochondrial permeability transition pore (PTP), a nonspecific large conductance pore whose ...opening leads to cell death and has been implicated in ischemia/reperfusion injury in multiple organs, in neurodegenerative disorders, and in muscular dystrophies. While the main target of CypD is a matter of ongoing research, inhibiting CypD protects in models of those diseases making it an interesting therapeutic target. The present review focuses on post-translational modifications of CypD that have been identified by recent studies, which can alter the regulation of the PTP and contribute to understanding the mechanisms of action of CypD.
To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients.
Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases ...the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT.
Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery.
A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life.
Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery.
Background
Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). Existing evidence for the effectiveness of NPWT on ...postoperative wounds healing by primary closure remains uncertain.
Objectives
To assess the effects of NPWT for preventing SSI in wounds healing through primary closure, and to assess the cost‐effectiveness of NPWT in wounds healing through primary closure.
Search methods
In January 2021, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In‐Process & Other Non‐Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries and references of included studies, systematic reviews and health technology reports. There were no restrictions on language, publication date or study setting.
Selection criteria
We included trials if they allocated participants to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with another.
Data collection and analysis
At least two review authors independently assessed trials using predetermined inclusion criteria. We carried out data extraction, assessment using the Cochrane risk of bias tool, and quality assessment according to Grading of Recommendations, Assessment, Development and Evaluations methodology. Our primary outcomes were SSI, mortality, and wound dehiscence.
Main results
In this fourth update, we added 18 new randomised controlled trials (RCTs) and one new economic study, resulting in a total of 62 RCTs (13,340 included participants) and six economic studies. Studies evaluated NPWT in a wide range of surgeries, including orthopaedic, obstetric, vascular and general procedures. All studies compared NPWT with standard dressings. Most studies had unclear or high risk of bias for at least one key domain.
Primary outcomes
Eleven studies (6384 participants) which reported mortality were pooled. There is low‐certainty evidence showing there may be a reduced risk of death after surgery for people treated with NPWT (0.84%) compared with standard dressings (1.17%) but there is uncertainty around this as confidence intervals include risk of benefits and harm; risk ratio (RR) 0.78 (95% CI 0.47 to 1.30; I2 = 0%). Fifty‐four studies reported SSI; 44 studies (11,403 participants) were pooled. There is moderate‐certainty evidence that NPWT probably results in fewer SSIs (8.7% of participants) than treatment with standard dressings (11.75%) after surgery; RR 0.73 (95% CI 0.63 to 0.85; I2 = 29%). Thirty studies reported wound dehiscence; 23 studies (8724 participants) were pooled. There is moderate‐certainty evidence that there is probably little or no difference in dehiscence between people treated with NPWT (6.62%) and those treated with standard dressing (6.97%), although there is imprecision around the estimate that includes risk of benefit and harms; RR 0.97 (95% CI 0.82 to 1.16; I2 = 4%). Evidence was downgraded for imprecision, risk of bias, or a combination of these.
Secondary outcomes
There is low‐certainty evidence for the outcomes of reoperation and seroma; in each case, confidence intervals included both benefit and harm. There may be a reduced risk of reoperation favouring the standard dressing arm, but this was imprecise: RR 1.13 (95% CI 0.91 to 1.41; I2 = 2%; 18 trials; 6272 participants). There may be a reduced risk of seroma for people treated with NPWT but this is imprecise: the RR was 0.82 (95% CI 0.65 to 1.05; I2 = 0%; 15 trials; 5436 participants). For skin blisters, there is low‐certainty evidence that people treated with NPWT may be more likely to develop skin blisters compared with those treated with standard dressing (RR 3.55; 95% CI 1.43 to 8.77; I2 = 74%; 11 trials; 5015 participants). The effect of NPWT on haematoma is uncertain (RR 0.79; 95 % CI 0.48 to 1.30; I2 = 0%; 17 trials; 5909 participants; very low‐certainty evidence). There is low‐certainty evidence of little to no difference in reported pain between groups. Pain was measured in different ways and most studies could not be pooled; this GRADE assessment is based on all fourteen trials reporting pain; the pooled RR for the proportion of participants who experienced pain was 1.52 (95% CI 0.20, 11.31; I2 = 34%; two studies; 632 participants).
Cost‐effectiveness
Six economic studies, based wholly or partially on trials in our review, assessed the cost‐effectiveness of NPWT compared with standard care. They considered NPWT in five indications: caesarean sections in obese women; surgery for lower limb fracture; knee/hip arthroplasty; coronary artery bypass grafts; and vascular surgery with inguinal incisions. They calculated quality‐adjusted life‐years or an equivalent, and produced estimates of the treatments' relative cost‐effectiveness. The reporting quality was good but the evidence certainty varied from moderate to very low. There is moderate‐certainty evidence that NPWT in surgery for lower limb fracture was not cost‐effective at any threshold of willingness‐to‐pay and that NPWT is probably cost‐effective in obese women undergoing caesarean section. Other studies found low or very low‐certainty evidence indicating that NPWT may be cost‐effective for the indications assessed.
Authors' conclusions
People with primary closure of their surgical wound and treated prophylactically with NPWT following surgery probably experience fewer SSIs than people treated with standard dressings but there is probably no difference in wound dehiscence (moderate‐certainty evidence). There may be a reduced risk of death after surgery for people treated with NPWT compared with standard dressings but there is uncertainty around this as confidence intervals include risk of benefit and harm (low‐certainty evidence). People treated with NPWT may experience more instances of skin blistering compared with standard dressing treatment (low‐certainty evidence). There are no clear differences in other secondary outcomes where most evidence is low or very low‐certainty. Assessments of cost‐effectiveness of NPWT produced differing results in different indications. There is a large number of ongoing studies, the results of which may change the findings of this review. Decisions about use of NPWT should take into account surgical indication and setting and consider evidence for all outcomes.
As a simple and versatile method, diffusion driven Layer-by-Layer assembly (dd-LbL) is developed to assemble graphene oxide (GO) into three-dimensional (3D) structure. The assembled GO macrostructure ...can be reduced through a hydrothermal treatment and used as a high volumetric capacitance electrode in supercapacitors. In this report we use rGO framework created from dd-LbL as a scaffold for in situ polymerization of aniline within the pores of the framework to form rGO/polyaniline (rGO/PANI) composite. The rGO/PANI composite affords a robust and porous structure, which facilitates electrolyte diffusion and exhibits excellent electrochemical performance as binder-free electrodes in a sandwich-configuration supercapacitor. Combining electric double layer capacitance and pseudo-capacitance, rGO/PANI electrodes exhibit a specific capacitance of 438.8 F g−1 at discharge rate of 5 mA (mass of electrodes were 10.0 mg, 0.5 A g−1) in 1 mol L−1 H2SO4 electrolyte; furthermore, the generated PANI nanoparticles in rGO template achieve a higher capacitance of 763 F g−1. The rGO/PANI composite electrodes also show an improved recyclability, 76.5% of capacitance retains after recycled 2000 times.
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•3D porous rGO is prepared by diffusion driven layer-by-layer assembly.•Polyaniline (PANI) nanoparticles are in-situ grown within the pores of 3D rGO.•As-prepared rGO/PANI was used as binder-free electrodes for supercapacitor.•The rGO/PANI exhibits capacitance of 438.8 F g−1 at 0.5 A g−1 in 1 M H2SO4.•PANI particles achieve a higher capacitance of 763 F g−1 at 0.5 A g−1.
We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized ...participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.
Abstract
Background
Outbreaks of coronavirus disease 2019 (COVID-19) have been reported in nursing homes and assisted living facilities; however, the extent of asymptomatic and presymptomatic severe ...acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this high-risk population remains unclear.
Methods
We conducted an investigation of the first known outbreak of SARS-CoV-2 at a skilled nursing facility (SNF) in Illinois on 15 March 2020 and followed residents for 30 days. We tested 126/127 residents for SARS-CoV-2 via reverse-transcription polymerase chain reaction and performed symptom assessments. We calculated the point prevalence of SARS-CoV-2 and assessed symptom onset over 30-day follow-up to determine: (1) the proportion of cases who were symptomatic, presymptomatic, and asymptomatic and (2) incidence of symptoms among those who tested negative. We used the Kaplan-Meier method to determine the 30-day probability of death for cases.
Results
Of 126 residents tested, 33 had confirmed SARS-CoV-2 on 15 March. Nineteen (58%) had symptoms at the time of testing, 1 (3%) developed symptoms over follow-up, and 13 (39%) remained asymptomatic. Thirty-five residents who tested negative on 15 March developed symptoms over follow-up; of these, 3 were re-tested and 2 were positive. The 30-day probability of death among cases was 29%.
Conclusions
SNFs are particularly vulnerable to SARS-CoV-2, and residents are at risk of severe outcomes. Attention must be paid to preventing outbreaks in these and other congregate care settings. Widespread testing and infection control are key to help prevent COVID-19 morbidity and mortality in these high-risk populations.
In an investigation of the first known outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a skilled nursing facility in Illinois, we found that 39% of confirmed cases remained asymptomatic, and the 30-day probability of death was 29%.
eReferral--a new model for integrated care Chen, Alice Hm; Murphy, Elizabeth J; Yee, Jr, Hal F
The New England journal of medicine,
06/2013, Volume:
368, Issue:
26
Journal Article
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