Links between COVID-19 and Alzheimer's Disease-What Do We Already Know?

Alzheimer's disease (AD) is a life-changing condition whose etiology is explained by several hypotheses. Recently, a new virus contributed to the evidence of viral involvement in AD: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 coronavirus disease. AD was found to be one of the most common COVID-19 comorbidities, and it was found to increase mortality from this disease as well. Moreover, AD patients were observed to present with the distinct clinical features of COVID-19, with delirium being prevalent in this group. The SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is overexpressed in brains with AD, which thus increases the viral invasion. Furthermore, the inhibition of the ACE2 receptor by the SARS-CoV-2 virus may also decrease the brain-derived neurotrophic factor (BDNF), contributing to neurodegeneration. The ApoE ε4 allele, which increases the risk of AD, was found to facilitate the SARS-CoV-2 entry into cells. Furthermore, the neuroinflammation and oxidative stress existing in AD patients enhance the inflammatory response associated with COVID-19. Moreover, pandemic and associated social distancing measures negatively affected the mental health, cognitive function, and neuro-psychiatric symptoms of AD patients. This review comprehensively covers the links between COVID-19 and Alzheimer's disease, including clinical presentation, molecular mechanisms, and the effects of social distancing.

Heat Shock Protein 27 Is an Emerging Predictor of Contrast-Induced Acute Kidney Injury on Patients Subjected to Percutaneous Coronary Interventions.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication associated with considerable morbidity and mortality. Heat-shock protein 27 (HSP27) plays a role in the defense of the kidney tissue against various forms of cellular stress, including hypoxia and oxydative stress, both features associated with CI-AKI. The aim of our study was to evaluate a potential predictive value of HSP27 for CI-AKI in patients subjected to percutaneous coronary interventions (PCI). Included were 343 selected patients subjected to PCI. Exclusion criteria were conditions that potentially might influence HSP27 levels. HSP27 serum levels were evaluated prior to PCI, together with serum creatinine, the concentration of which was also evaluated twice at 48 and 72 h post PCI. CI-AKI was diagnosed in 9.3% of patients. Patients in whom CI-AKI was diagnosed were older (p < 0.001), were more often females (p = 0.021), had higher prevalence of diabetes (p = 0.011), hypotension during PCI (p < 0.001), albuminuria (p = 0.004) as well as multivessel disease (p = 0.002), received higher contrast volume (p = 0.006), more often received contrast volume (CV) above the maximum allowed contrast dose (MACD) (p < 0.001), and had lower HSP27 level (p < 0.001). On multivariate analysis, CV > MACD (OR 1.23, p = 0.001), number of diseased vessels (OR 1.27, p = 0.006), and HSP27 (OR 0.81, p = 0.001) remained independent predictors of CI-AKI. Low concentration of HSP27 is an emerging, strong and independent predictor of CI-AKI in patients subjected to PCI.

The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis.

BACKGROUND: Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs). METHODS: Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT. RESULTS: An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement. CONCLUSIONS: RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.

Serum heat shock protein 27 levels predict cardiac mortality in hemodialysis patients.

BACKGROUND: Decreased heat shock protein 27 (HSP27) participates in many processes that are involved in cardiovascular (CV) disease. The objective of the study was to evaluate if HSP27 level was predictive of mortality as well as to evaluate factors associated with HSP27 level in a group of patients treated with HD. METHODS: Enrolled to the study were 202 HD patients. Clinical data, biochemical, echocardiographic, and carotid atherosclerosis parameters were evaluated. Patients were splited into groups on the basis of the cut-off lower and higher 50th percentile of serum HSP27 levels, and were followed-up for 28.68 ± 6.12 months. RESULTS: No significant difference was observed between serum HSP27 levels in patients and controls. Low HSP27 patients were older, had higher left ventricular mass index, lower ejection fraction, higher prevalence of diabetes, myocardial infarction and carotid atherosclerosis, higher C-reactive protein level, and worse oxidant/antioxidant status. The multiple regression analysis identified that HSP27 levels were independently, negatively associated with serum oxidized LDL and the number of carotid plaques. Using the Kaplan-Meier analysis it was shown that the cumulative incidences of both CV and sudden cardiac death (SCD) mortality were higher in low HSP27 group in comparison with high serum HSP27 group. A multivariate Cox analysis showed that HSP27 level is an independent and strong predictor of CV as well as SCD mortality. CONCLUSIONS: Low serum HSP27 level is independently associated with both CV and SCD mortality but not with all-cause mortality. Low serum HSP27 level is associated with carotid atherosclerosis and oxidative stress.

Factors influencing P terminal force in lead V1 of the ECG in hemodialysis patients.

INTRODUCTION: Atrial fibrillation (AF) is a highly prevalent arrhythmia in hemodialysis (HD) patients, and an HD session may be a trigger for AF episodes. An abnormal P-terminal force in lead V1 (PTFV1) may predict new-onset AF in HD patients. The aim of the study was to assess the influence of the HD process on PTFV1 and to evaluate possible factors influencing PTFV1 in a group of selected HD patients. MATERIAL AND METHODS: One hundred and fifty-three selected HD patients entered the study. Blood chemistry, electrocardiography, and impedance cardiography were evaluated before and after HD. Echocardiography was performed on the morning after dialysis. Abnormal PTFV1 was defined as PTFV1 > 40 mm × ms. RESULTS: Abnormal PTFV1 was found in 35.3% of patients before dialysis and in 48.4% of patients after dialysis. The results of multiple regression analysis revealed that the independent predictors of pre-dialysis abnormal PTFV1 were: left atrial volume index (p = 0.002), left ventricular mass index (p = 0.014), and pre-dialysis thoracic fluid content (p = 0.021) values. The independent predictors of HD-induced abnormal PTFV1 values were larger differences between pre-dialysis and post-dialysis values of serum potassium (p < 0.001) and mean arterial pressure (p = 0.008). CONCLUSIONS: Abnormal PTFV1 is prevalent in HD patients. The HD process adversely affects PTFV1 values. Pre-dialysis abnormal PTFV1 is mainly associated with structural heart abnormalities and hydration status. HD-induced abnormal PTFV1 is associated predominantly with serum potassium changes as well as HD-induced hypotension. Our results suggest possible risk factors for AF; however, their clinical significance needs to be confirmed in follow-up studies.

Syndecan-4 Is an Independent Predictor of All-Cause as Well as Cardiovascular Mortality in Hemodialysis Patients.

BACKGROUND: Left ventricular hypertrophy is associated withincreased mortality in hemodialysis (HD) patients.Syndecan-4 plays a role in many processes that are involved in the heart fibrosis and hypertrophy.We designed this study to prospectively determine whether syndecan-4 was predictive of mortality in a group of HD patients. METHODS: In total, 191 HD patients were included. Clinical, biochemical and echocardiographic parameters were recorded. HD patients were followed-up for 23.18 ± 4.02 months. RESULTS: Syndecan-4 levels correlated strongly with geometrical echocardiographic parameters and ejection fraction. Relations with pressure-related parameters were weak and only marginally significant. Using the receiver operating characteristics the optimal cut-off points in predicting all-cause as well as cardiovascular (CV) mortality were evaluated and patients were divided into low and high syndecan-4 groups. A Kaplan-Meier analysis showed that the cumulative incidences of all-cause as well as CV mortality were higher in high serum syndecan-4 group compared with those with low serum syndecan-4 (p<0.001 in both cases).A multivariate Cox proportional hazards regression analysis revealed syndecan-4 concentration to be an independent and significant predictor of all-cause (hazard ratio, 2.99; confidence interval, 2.34 to 3.113; p<0.001)as well as CV mortality (hazard ratio, 2.81;confidence interval, 2.28to3.02; p<0.001). CONCLUSIONS: Serum syndecan-4 concentration reflects predominantly geometrical echocardiographic parameters. In HD patients serum syndecan-4 concentration is independently associated with all-cause as well as CV mortality.

An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.

Evaluation of high-mobility group box 1 protein concentration in serum of patients with M. tuberculosis infection.

Infection with Mycobacterium tuberculosis is accompanied by an intense inflammatory response. Recently, a new mediator of inflammation, HMGB1 protein has been identified that contributes to acute lung injury. However, its role in the systemic inflammatory response in tuberculosis has not been thoroughly investigated. We investigated the systemic levels of HMGB1 and TNF-α in patients with active and latent lung tuberculosis as a prognostic marker of disease activity. The study was performed to 70 patients with confirmed Mycobacterium tuberculosis infection and other than tuberculosis lung diseases and in 20 healthy persons. Serum HMGB1 and TNF-α concentrations were measured by ELISA. The highest concentration of HMGB1 was detected in the bloodstream of people with Mtb infection (latent and active). Its concentration increased significantly in sera of patients with active tuberculosis (47.5 ng/ml), compared to patients with other lung diseases (36.87 ng/ml). TNF-α had significantly higher concentration in a patients group compared to healthy controls, with the highest concentration in the LTBI group of patients (0.136 ng/ml). We observed a strong positive correlation between TNF-α and HMGB1 concentrations in patients with tuberculosis infections. We conclude that HMGB1 is secreted during active and latent tuberculosis in the highest amounts compared to other lung diseases.

[Evaluation of Th1/Th2 lymphocyte balance and lipopolysaccharide receptor expression in asthma patients]. / Ocena równowagi limfocytów Th1/Th2 oraz ekspresji receptorów dla lipopolisacharydu u chorych na astme.

INTRODUCTION: An increase in the number of asthma patients which has recently been observed depends on their place of residence and their occupation. This suggests that both external factors and genetic predispositions affect the development of the disease. The contact with bacterial lypopolysaccharide (LPS) may suppress the development of asthma among rural inhabitants. The mechanism of LPS effect most probably consists in the activation of macrophages and granulocytes by TLR4 and CD14 receptors for the production of cytokines, which affect Th1/Th2 balance. The objective of the study was the evaluation of CD14 and TLR4 expression on mononuclear cells and the analysis of Th1/Th2 balance in peripheral blood among asthma patients. MATERIAL AND METHODS: The study group covered 22 patients with bronchial asthma (mean age 45 +/- 15), and was conducted by the method of flow cytometry with the use of fluorochrome-labelled monoclonal antibodies. CD14 and TLR expression was assessed in peripheral blood monocytes. Th1/Th2 balance was determined by the measurement of intracellular IL-2, IFN-gamma, IL-4 and IL-10 expression in T-helper cells after culture with the stimulation of cytokine production. RESULTS: A negative correlation was noted between TLR4 expression and the percentage of Th2 lymphocytes, while a positive correlation was observed between expression of TLR4 and percentage of Th1 cells. No relationship was found between CD14 expression on monocytes and the percentage of Th1 and Th2 lymphocytes. CONCLUSIONS: An increased percentage of lymphocytes with TLR4 expression is associated with the change in Th1/Th2 balance in favour of Th1 lymphocytes in asthma patients.