ß-Hydroxybutyrate and melatonin suppress maladaptive UPR, excessive autophagy and pyroptosis in Aß 1-42 and LPS-Induced SH-SY5Y cells.

BACKGROUND: Alzheimer's disease is a neurological disease characterized by the build-up of amyloid beta peptide (Aß) and lipopolysaccharide (LPS), which causes synapse dysfunction, cell death, and neuro-inflammation. A maladaptive unfolded protein response (UPR), excessive autophagy, and pyroptosis aggravate the disease. Melatonin (MEL) and hydroxybutyrate (BHB) have both shown promise in terms of decreasing Aß pathology. The goal of this study was to see how BHB and MEL affected the UPR, autophagy, and pyroptosis pathways in Aß1-42 and LPS-induced SH-SY5Y cells. MATERIALS AND METHODS: Human neuroblastoma SH-SY5Y cells were treated with BHB, MEL, or a combination of the two after being exposed to A ß1-42 and LPS. Cell viability was determined using the MTT test, and gene expression levels of UPR (ATF6, PERK, and CHOP), autophagy (Beclin-1, LC3II, P62, and Atg5), and pyroptosis-related markers (NLRP3, TXNIP, IL-1ß, and NFκB1) were determined using quantitative Real-Time PCR (qRT-PCR). For statistical analysis, one-way ANOVA was employed, followed by Tukey's post hoc test. RESULTS: BHB and MEL significantly increased SH-SY5Y cell viability in the presence of A ß1-42 and LPS. Both compounds inhibited the expression of maladaptive UPR and autophagy-related genes, as well as inflammatory and pyroptotic markers caused by Aß1-42 and LPS-induced SH-SY5Y cells. CONCLUSION: BHB and MEL rescue neurons in A ß1-42 and LPS-induced SH-SY5Y cells by reducing maladaptive UPR, excessive autophagy, and pyroptosis. More research is needed to fully comprehend the processes behind their beneficial effects and to discover their practical applications in the treatment of neurodegenerative disorders.

Impact of Obesity on Cardiac Volumes and Left Ventricular Diameter: A Cross-Sectional Study in an Iranian Heart Center.

Introduction: Obesity, a pressing global health issue worldwide, contributes to risk factors such as hypertension and dyslipidemia, creating an unfavorable cardiovascular environment and increasing the likelihood of adverse cardiac events. His study aims to assess the impact of obesity on various cardiovascular parameters. Methods: A cross-sectional analysis was conducted at a Heart Center, focusing on adults admitted for suspected heart diseases. The dataset included information on demographics, clinical history, laboratory results, and echocardiography. Descriptive analysis and multiple linear regression were employed using IBM SPSS Statistics version 26. Results: The study of 105 individuals with suspected heart diseases revealed prevalent health factors such as hypertension (47.6%) and hyperlipidemia (61%). Body mass index (BMI) averaged 30, indicating a trend toward overweight. Obesity significantly associated with higher systolic blood pressure (SBP, p=0.005) and diastolic blood pressure (DBP, p=0.002), larger cardiac volumes (end-diastolic volume, EDV, p=0.013; end-systolic volume, ESV, p=0.040), and a marginally significant influence on left ventricular end-diastolic diameter (LVEDD, p=0.068). No significant associations were found with left ventricular end-systolic diameter (LVEDS), heart rate (HR), or ejection fraction (EF). Conclusions: Our study highlights a significant association between obesity and elevated blood pressure, larger cardiac volumes, and a marginal impact on left ventricular end-diastolic diameter. While caution is needed in inferring causation due to the study's cross-sectional nature, these findings underscore the importance of addressing obesity as a potential risk factor for adverse cardiovascular outcomes. Further investigations are warranted to enhance our understanding of the complex interplay between obesity and cardiovascular health.

A case report of diabetic ketoacidosis due to endocarditis of the mitral valve.

In the context of diabetic ketoacidosis, clinicians should consider uncommon origins of infection, notably infective endocarditis. This is especially crucial when confronted with cases that recur persistently or exhibit resistance to treatment. This is a case of a diabetic patient with diabetic ketoacidosis admitted to our facility. A 35-year-old diabetic patient presented with DKA precipitated by mitral valve endocarditis. To our knowledge and according to the literature review, only one case of DKA precipitated by endocarditis has been reported in the past. This report highlights the importance of considering endocarditis as a possible etiology in patients presenting.

Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Introduction: Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking. Methods: We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI). Results: We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (-14.06 mg/dl; 95% CI -18.0 to -10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group. Conclusions: Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.

Influenza vaccination and major cardiovascular risk: a systematic review and meta-analysis of clinical trials studies.

Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL up to 1 August 2023. Meta-analysis and stratified analyses were performed to investigate specific outcomes, including myocardial infarction (MI), cardiovascular death, and stroke. Pooled relative risks (RR) along with their 95% confidence intervals (CI) were calculated to evaluate the associations. A comprehensive analysis was conducted on a total of 9059 patients, with 4529 patients receiving the influenza vaccine and 4530 patients receiving a placebo. Among patients who received the influenza vaccine, a notable reduction in the occurrence of major cardiovascular events was observed, with 517 cases compared to 621 cases in the placebo group (RR 0.70; 95% CI 0.55-0.91). The stratified analysis revealed a decreased risk of MI in vaccinated patients (RR 0.74; 95% CI 0.56-0.97) and a significant reduction in cardiovascular death events (RR 0.67; 95% CI 0.45-0.98). This study provides compelling evidence that influenza vaccination is associated with a decreased risk of major cardiovascular events, particularly myocardial infarction, and cardiovascular death. These findings highlight the potential of influenza vaccination as an adjunctive strategy in cardiovascular disease prevention. Further research and exploration of underlying mechanisms are warranted to elucidate the observed beneficial effects.

COVID-19 and Acute Kidney Injury: A Systematic Review.

Introduction: Acute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19. Methods: We searched PubMed/Medline, Web of Science, and Embase for the relevant scientific literature published up to February 1, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", and "Acute kidney injury". Results: Forty-four studies with a total number of 114 COVID-19 patients with AKI (Mean age: 53.6 years) were included in our systematic review. The most common comorbidities in patients with COVID-19 suffering from AKI were the history of diabetes, hypertension, and hyperlipidemia. Twelve out of the 44 included studies reported a history of chronic kidney disease (CKD) in this group of patients. Focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis (ATN) were the most common pathological evidence. The average length of hospital stay was 19 days, and the average duration of need for mechanical ventilation was 3 days. Conclusions: The current systematic review shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, prolonged duration of hospitalization, and poor prognosis. Given the extent of the adverse impact of AKI, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.

COVID-19 in patients with and without acute kidney injury.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 as the newest member of Beta-Coronaviruses can cause a complicated disease called COVID-19. This virus is able to penetrate a broad range of human cells, such as liver, heart, and kidney cells via ACE2-associated endocytosis. Heart involvement can result in kidney injuries; it is now testified that kidney congestion occurs following the cardio-renal syndrome. Acute Kidney Injury is one of the most critical damages to the kidney in a wide range of COVID-19-caused kidney injuries (which includes proteinuria, hematuria, etc.). Examination of AKI risk factors in COVID-19 patients can assist physicians to prevent its incidence. The final aim of this systematic review was to collate the condition and risk factors of AKI and non-AKI COVID-19 patients and to investigate AKI incidence in high-risk patients. METHOD: A complete and comprehensive survey was performed by reviewing original articles and case reports indexed in various databases such as PubMed/Medline, Embase, and WoS to find appropriate articles. The eligible articles then were selected by two authors and entered into the evaluation process. This systematic review conforms PRISMA statement. RESULTS: After searching for potentially relevant articles, 14 out of the initial 463 articles from 6 countries were selected and evaluated. All of eligible articles have investigated the rate of AKI incidence and its physio-pathological consequences in COVID-19 patients in all conditions (not only patients in critical condition). First, the initial differences between AKI and non-AKI patients were compared. As an instance, our study revealed that mean of White Blood cells (WBC) was much higher in AKI patients which can be responsible for the severe conditions. Then, other variations like differences in laboratory and imaging findings were compared between these two groups. Our outcomes demonstrated that the presence of diabetes mellitus (DM), hypertension (HTN), and male sex can be three significant risk factors in AKI incidence in COVID-19 patients. Fatality rate and treatment methods were also compared among these two groups. CONCLUSION: As one of kidney damages, AKI can worsen COVID-19 patients' status by causing conditions such as acidosis. Our study shows the common symptoms in AKI COVID-19 patients were fever, cough, and malaise. The results of our study can help physicians to arrange COVID-19 with AKI patients' treatment strategy precisely (Tab. 8, Fig. 1, Ref. 48).

Is cardiac Troponin I Considered as A Predictor of In-hospital Mortality among COVID-19 Patients? A Retrospective Cohort Study.

OBJECTIVE: To describe the levels of troponin I in COVID-19 patients and its role in the prediction of their in-hospital mortality as a cardiac biomarker. METHODS: The current retrospective cohort study was performed on the clinical records of 649 COVID-19-related hospitalized cases with at leat one positive polymerase chain reaction (PCR) test in Tehran, Iran from February 2020 to early June 2020. The on admission troponin I level divided into two groups of ≤0.03ng/mL (normal) and >0.03ng/mL (abnormal). The adjusted COX-regression model was used to determine the relationship between the studied variables and patient's in-hospital mortality. RESULTS: In this study, the median age of subjects was 65 years (54.8% men) and 29.53% of them had abnormal troponin I levels. Besides, the in-hospital mortality rate among patients with abnormal troponin I levels was found to be 51.56%; whereas, patients with normal levels exhibited 18.82% mortality. Also, the multivariable analysis indicated that the risk of death among hospitalized COVID-19 patients displaying abnormal troponin I levels was 67% higher than those with normal troponin I levels (Hazard ratio=1.67, 95% confidence interval=1.08-2.56, p=0.019). CONCLUSION: It seems that troponin I is one of the important factors related to in-hospital mortality of COVID-19 patients. Next, due to the high prevalence of cardiac complications in these patients, it is highly suggested to monitor and control cardiac biomarkers along with other clinical factors upon the patient's arrival at the hospital.

Evaluation of Microleakage at the Junction Between Combined Amalgam/Composite Resin Restorations Using Different Bonding Systems in Class II Cavities

Abstract Objective: To evaluate the microleakage at the junction between amalgam-composite resin restorations using different bonding systems. Material and Methods: In this in-vitro study, standard class II cavities were prepared on 40 human maxillary premolars. The axial and gingival floor depths of the cavities were 2 mm and 1 mm below (cementoenamel junction), respectively. The samples were divided into 4 groups (n = 10). In all groups, a layer of 1-mm thick amalgam was used as a coating for the initial part of the gingival floor. In group 1, no bonding system was used for amalgam restoration. In group 2, G-Premio Bond was applied. G-Premio bond + alloy primer and single bond + alloy primer were used in group 3 and group 4, respectively. The rest of the cavities in all groups were then repaired using FiltekZ250 composite. The samples were thermocycled at 500 rpm and immersed in 1% methylene blue solution for 24 hours to allow dye penetration. Once cut, the samples were placed under a stereomicroscope (40X) to determine the microleakage rate. Data analysis was carried out using post-hoc and Chi-square tests (p<0.05). Results: The highest and lowest microleakage rate was related to groups 1 and 3, respectively. There was a significant difference between groups (1,2) and (1,3), and (1,4), and groups (2,3) (p<0.05). Conclusion: The use of alloy primer and bonding could reduce the microleakage between the two restorations (AU).

Neurological Complications of COVID-19: A Rare Case of Bilateral Blindness.

BACKGROUND: There are growing reports of the neurological involvement among patients with coronavirus disease 2019 (COVID-19). Headache, confusion, and anosmia after olfactory nerve disruption are the most prevalent presentation of the neurological involvement related to COVID-19. However, small numbers of the central nervous system involvement have been reported. CASE REPORT: A 49-year-old man was referred to our hospital with abrupt vision loss. Three weeks earlier he was admitted to the hospital based on his respiratory symptoms and was diagnosed with COVID-19 infection. Initial brain magnetic resonance imaging indicated diffuse restricted bilateral foci in both parietal and occipital lobes in favor of acute infarction. Diffuse weighted imaging demonstrated restricted bilateral hyperintense signals in parietal and occipital region. Occipital cortex biopsy showed brain tissue with focal infiltration of foamy macrophages mixed with reactive astrocytes and no plasma cell infiltration. Considering all of the evidence, post-COVID-19 encephalitis diagnosis was considered for the patient, and methyl prednisolone pulse therapy and intravenous immunoglobulin were initiated. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although there are growing reports of neurological involvement among patients, blindness is rarely observed as a complication of post-COVID-19 encephalitis. To our knowledge, this is the first case of post-COVID-19 encephalitis that presented with bilateral vision loss primarily. This case may raise physicians' awareness of neurological complications of COVID-19.

Medical treatment for paradoxical and saddle pulmonary embolism in a young man with patent foramen ovale and coronavirus disease 2019.

Here, we reported a 32-year-old male presenting to the emergency department with respiratory symptoms and coronavirus disease 2019 (COVID-19) diagnosis. Multiple thrombi were detected in his heart and inferior vena cava, probably due to former deep-vein thrombosis. The presence of patent foramen ovale and high pressure of the right heart caused the clots to enter the heart's left side. He received fibrinolytics, and his condition improved with no need for surgery. Hence, patients with impending paradoxical embolism may take advantage of medical treatment, such as fibrinolytics. Moreover, COVID-19 appears to be associated with a strong thrombotic tendency, and anticoagulants might be helpful.

COVID-19 and Cardiomyopathy: A Systematic Review.

Background: Cardiomyopathies (CMPs) due to myocytes involvement are among the leading causes of sudden adolescent death and heart failure. During the COVID-19 pandemic, there are limited data available on cardiac complications in patients with COVID-19, leading to severe outcomes. Methods: We conducted a systematic search in Pubmed/Medline, Web of Science, and Embase databases up to August 2020, for all relevant studies about COVID-19 and CMPs. Results: A total of 29 articles with a total number of 1460 patients were included. Hypertension, diabetes, obesity, hyperlipidemia, and ischemic heart disease were the most reported comorbidities among patients with COVID-19 and cardiomyopathy. In the laboratory findings, 21.47% of patients had increased levels of troponin. Raised D-dimer levels were also reported in all of the patients. Echocardiographic results revealed mild, moderate, and severe Left Ventricular (LV) dysfunction present in 17.13, 11.87, and 10% of patients, respectively. Conclusions: Cardiac injury and CMPs were common conditions in patients with COVID-19. Therefore, it is suggested that cardiac damage be considered in managing patients with COVID-19.

A Novel VPS13B Mutation Identified by Whole-Exome Sequencing in Iranian Patients with Cohen Syndrome.

Cohen syndrome is caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B, also referred to as COH1) gene on chromosome 8q22.2. The VPS13B protein is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Clinical manifestations of Cohen syndrome are mainly intellectual disability, developmental delay, facial abnormalities, and eye disorders. This study aimed to identify the causative variant in two unrelated families with Cohen syndrome. To this end, whole-exome sequencing (WES) was performed to identify the pathogenic variants. A homozygous nonsense variant (NM_017890:c.10369C > T; NP_060360.3: p.Q3457X) in the VPS13B gene was identified and co-segregated with all affected individuals in both families. In silico analysis highly suggested this variant as damaging for protein function. The present study increases the mutation spectrum of the VPS13B gene and could be useful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

Dual antiplatelet therapy before coronary artery bypass grafting in patients with myocardial infarction: a prospective cohort study.

BACKGROUND: Dual antiplatelet therapy (DAPT) in patients with MI who are candidates for early coronary artery bypass grafting (CABG) can affect intraoperative and postoperative outcomes. Therefore, the aim of this study was to evaluate the effect of DAPT up to the day before CABG on the outcomes during and after surgery in patients with MI. METHODS: In this prospective cohort study, 224 CABG candidate patients with and without MI were divided into two groups: (A) patients without MI who were treated with aspirin 80 mg/day before surgery (noMI-aspirin group; n = 124) and (B) patients with MI who were treated with aspirin 80 mg/day before surgery and clopidogrel (Plavix brand) at a dose of 75 mg/day (MI-DAPT group; n = 120). Dual or mono-antiplatelet therapy continued until the day before surgery. Patients were followed to assess in-hospital and 6-months outcomes. RESULTS: The in-hospital mortality in MI-DAPT group was similar with noMI-aspirin group (OR 4.2; 95% CI 0.9-20.5; p = 0.071). The prevalence of CVA (p = 0.098), duration of hospital stay (p = 0.109), postoperative ejection fraction level (p = 0.693), diastolic dysfunction grade (p = 0.651) and postoperative PAP level (p = 0.0364) did not show difference between two groups. No mild or severe bleeding was observed in the patients. Six-month follow up showed that number of readmissions (p = 0.801), number of cases requiring angiography (p = 0.100), cases requiring re-PCI (p = 0.156), need for re-CABG (p > 0.999) and CVA (p > 0.999) did not differ between the two groups. During the 6-month follow-up, out-hospital mortality did not differ significantly between the two groups (p = 0.446). CONCLUSIONS: A 6-month follow-up showed that DAPT with aspirin and clopidogrel before CABG in patients with MI has no effect on postoperative outcomes more than mono-APT with aspirin. Therefore, DAPT is recommended in the preoperative period for these patients.

Interaction effect of myocardial infarction and obesity on left atrial functions.

PURPOSE: To determine whether myocardial infarction (MI) would lead to a greater decrease in left atrial (LA) functions in subjects with than without obesity. METHODS: A total of 310 consecutive patients were divided into four groups according to the presence or absence of obesity and MI. The functions of the LA were evaluated in terms of longitudinal deformation of the LA myocardium via 2D speckle-tracking echocardiography. RESULTS: The adjusted analysis showed a reduction in the strain and strain rate during the reservoir and contraction phases and in the strain rate during the conduit phase in patients with MI and in subjects with obesity (P < .05). In addition, there was a significant interaction effect of obesity and MI on the strain rate during the contraction phase (P = .048). CONCLUSIONS: There is an independent and additional interaction effect of obesity and MI on the reservoir and conduit functions of the LA. MI was more deleterious to the contraction function in subjects without than with obesity, so that the contraction function was similar in MI patients without obesity and MI patients with obesity.

Interaction Effect of Diabetes and Acute Myocardial Infarction on the Left Atrial Function as Evaluated by 2-D Speckle-Tracking Echocardiography.

The aim of the study described here was to investigate, using 2-D speckle-tracking echocardiography, whether myocardial infarction (MI) leads to diminished left atrial function in diabetic patients by comparison with non-diabetic patients. A total of 310 consecutive patients were divided into four groups based on the presence or absence of diabetes mellitus (DM) and acute ST-elevation MI. In the adjusted analysis, systolic and early diastolic strain and strain rate were reduced in the diabetic patients. Additionally, all deformation markers were impaired in the patients with MI. The DM-MI interaction was not statistically significant. Although reservoir, conduit and contraction functions of the left atrium were reduced in the patients with MI, left atrial reservoir and conduit functions were decreased in the diabetic patients. The reduction in left atrial function caused by MI was similar for diabetic and non-diabetic patients. Thus, DM and MI additively damaged left atrial function.

Is the longitudinal deformation of the left ventricle affected by vitamin D deficiency in nondiabetics? A 2D speckle-tracking echocardiographic study.

OBJECTIVES: Vitamin D deficiency with its high global prevalence is associated with some pathological changes in the myocardium. The aim of our study was to assess the longitudinal deformation of the left ventricular (LV) myocardium in subjects with vitamin D deficiency. METHODS: This cross-sectional study recruited 98 consecutive nondiabetic subjects (45 subjects with vitamin D deficiency and 53 subjects without vitamin D deficiency) without significant epicardial coronary artery stenosis. The longitudinal subendocardial deformation indices of the LV myocardium were evaluated with 2D speckle-tracking echocardiography. RESULTS: The end-systolic strain, the systolic strain rate, and the early and late diastolic strain rates were not statistically significantly different between the subjects with and without vitamin D deficiency. CONCLUSIONS: The global longitudinal subendocardial deformations of the LV, including the systolic strain rate and the systolic and diastolic strain rates, as evaluated with 2D speckle-tracking echocardiography were not statistically significantly correlated with the presence or absence of vitamin D deficiency.