Myocardium at Risk Is Associated With Adverse Clinical Events in Women but Not in Men,After Coronary Artery Bypass Grafting

Background

Women undergoing coronary artery bypass grafting (CABG) are at increased risk for morbidity and mortality. Factors responsible for this observation include smaller coronary size and delayed presentation. To date, no studies have examined the effect of the degree of myocardium at risk (MAR) on the relationship between female sex and adverse postoperative events.

Methods

Consecutive patients undergoing first-time isolated CABG at a single institution from 2002-2007 were identified. MAR was calculated using the weighted Duke Index and was categorized as low, moderate, or high. Multivariable logistic regression models were created to compare the impact of MAR on adverse clinical events.

Results

We identified 3741 patients, 3325 (89%) of whom had complete angiographic data. Women (n = 755) were older (P = 0.0001) and presented more often with hypertension (P = 0.0001), diabetes (P = 0.0001), heart failure (P = 0.0001), and an urgent/emergent situation (P = 0.002). After surgery, women experienced greater rates of adverse events (15.2% vs 9.3%; P = 0.0001). In a fully adjusted logistic regression model, the nested interaction of sex in MAR showed that women had a significantly greater risk of major adverse cardiovascular events (MACE) when MAR was high (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3-2.6; P = 0.0004). Greater severity of MAR emerged as an independent predictor of adverse events among women (high: OR, 2.9; 95% CI, 1.2-7.3; moderate: OR, 2.2; 95% CI, 0.8-5.7; low: OR, 1.0), but not among men.

Conclusions

MAR was independently associated with higher rates of adverse events among women but not in men undergoing CABG. This finding may help explain differences in outcomes seen between women and men after revascularization.     

Up-regulation of D3 dopamine receptor mRNA by neuroleptics

The effects of 14 days neuroleptic treatment on the expression of the D₃ dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D₃ mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D₃ expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D₃ expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D₃ receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D₃ receptor up-regulation in the striatum. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley-Liss, Inc.     

Direct synthesis of amides and imines by dehydrogenative homo or cross-coupling of amines and alcohols catalyzed by Cu-MOF

Oxidative dehydrogenative homo-coupling of amines to imines and cross-coupling of amines with alcohols to amides was achieved with high to moderate yields at room temperature in THF using Cu-MOF as an efficient and recyclable heterogeneous catalyst under mild conditions. Different primary benzyl amines and alcohols could be utilized for the synthesis of a wide variety of amides and imines. The Cu-MOF catalyst could be recycled and reused four times without loss of catalytic activity.

Oxidative dehydrogenative homo or cross-coupling of amines with alcohols to imines and amides was achieved with high to moderate yields at room temperature using Cu-MOF as an efficient and recyclable heterogeneous catalyst.     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

Temporal definition of haematopoietic stem cell niches in a large animal model of in utero stem cell transplantation

The fetal sheep model has served as a biologically relevant and translational model to study in utero haematopoietic stem cell transplantation (IUHSCT), yet little is known about the ontogeny of the bone marrow (BM) niches in this model. Because the BMmicroenvironment plays a critical role in the outcome of haematopoietic engraftment, we have established the correlation between the fetal‐sheep and fetal‐human BM niche ontogeny, so that studies addressing the role of niche development at the time of IUHSCT could be accurately performed. Immunofluorescence confocal microscopic analysis of sheep fetal bone from gestational days (gd) 25–68 showed that the BM microenvironment commences development with formation of the vascular niche between 25 and 36 gd in sheep; correlating with the events at 10–11 gestational weeks (gw) in humans. Subsequently, between 45 and 51 gd in sheep (c. 14 gw in humans), the osteoblastic/endosteal niche started developing, the presence of CD34⁺ CD45⁺ cells were promptly detected, and their number increased with gestational age. IUHSCT, performed in sheep at 45 and 65 gd, showed significant haematopoietic engraftment only at the later time point, indicating that a fully functional BM microenvironment improved engraftment. These studies show that sheep niche ontogeny closely parallels human, validating this model for investigating niche influence/manipulation in IUHSCT engraftment.     

Protective effects of N-acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners

OBJECTIVE: Long-term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N-acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks. METHODOLOGY: Seventy-two male Wistar albino rats were used and divided into two groups: one group inhaled only thinners (TI), while the other inhaled TI plus NAC. Rats in the TI and TI + NAC groups were divided into four subgroups (each consisting of eight rats) according to the duration of exposure to TI: 2, 4, 6 and 8 weeks. A control group (n = 7) of rats inhaled neither TI nor NAC. Malondialdehyde (MDA) and GSH levels, and superoxide dismutase (SOD) activities were determined in the lung tissues. Histopathological findings were evaluated as acute and chronic changes in the alveoli and interstitium in the TI and TI + NAC groups and compared with those in the control group. RESULTS: While tissue MDA levels in the groups inhaling TI for 4, 6 and 8 weeks were significantly higher than those in the control groups (P < 0.01, P < 0.01, P < 0.0001, respectively), GSH levels were significantly lower (P < 0.05, P < 0.01, P < 0.01, respectively). Tissue SOD activities in the groups inhaling TI for 6 and 8 weeks were significantly lower than those in the control group (P < 0.05, P < 0.01, respectively). In the TI group, MDA levels were significantly increased (P < 0.01) with increasing duration of inhalation (from the second week through to the eighth week), while GSH levels and SOD activities were significantly decreased (P < 0.01, P < 0.01). Tissue MDA levels were significantly lower in the TI + NAC groups across all inhalation periods, when compared with the TI groups (P < 0.01, P < 0.0001, P < 0.0001, P < 0.0001, respectively). Tissue GSH levels in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.01, P < 0.01, P < 0.0001). Tissue SOD activities in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.0001, P < 0.05, P < 0.0001). Pathological examinations with light microscopy did not show any beneficial effect of NAC application in terms of deferring or alleviating the negative effects of TI. CONCLUSIONS: Thinners are agents that cause imbalance between oxidants and antioxidants produced by aerobic cellular systems. This imbalance between oxidant and antioxidant systems is decreased by the effect of NAC. However, ultrastructural studies may be needed to substantiate this evidence morphologically, as light microscopy was inconclusive.     

Outcomes of Patients with Recurrent and Refractory Lymphoma Undergoing Allogeneic Hematopoietic Cell Transplantation with BEAM Conditioning and Sirolimus- and Tacrolimus-Based GVHD Prophylaxis

The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n?=?12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT.     

Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death

Investigations into the cellular and molecular biology of genes that cause inherited forms of Parkinson's disease, as well as the downstream pathways that they trigger, shed considerable light on our understanding the fundamental determinants of life and death in dopaminergic neurons. Homozygous deletion or missense mutation in DJ-1 results in autosomal recessively inherited Parkinson's disease, suggesting that wild-type DJ-1 has a favorable role in maintaining these neurons. Here, we show that DJ-1 protects against oxidative stress-induced cell death, but that its relatively modest ability to quench reactive oxygen species is insufficient to account for its more robust cytoprotective effect. To elucidate the mechanism of this cell-preserving function, we have screened out the death protein Daxx as a DJ-1-interacting partner. We demonstrate that wild-type DJ-1 sequesters Daxx in the nucleus, prevents it from gaining access to the cytoplasm, from binding to and activating its effector kinase apoptosis signal-regulating kinase 1, and therefore, from triggering the ensuing death pathway. All these steps are impaired by the disease-causing L166P mutant isoform of DJ-1. These findings suggest that the regulated sequestration of Daxx in the nucleus and keeping apoptosis signal-regulating kinase 1 activation in check is a critical mechanism by which DJ-1 exerts its cytoprotective function.