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Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

Chronic prostatitis (CP) is a common inflammatory condition of the prostate that is estimated to effect 2%-10% of the world's male population. It can manifest as perineal, suprapubic, or lower back pain and urinary symptoms occurring with either recurrent bacterial infection [chronic bacterial prostatitis (CBP)] or in the absence of evidence of bacterial infection [chronic pelvic pain syndrome (CPPS)]. Here, in the case of a 39 years-old CBP patient, we report the first successful use of a bacteriophage-derived muralytic enzyme (endolysin) to treat and resolve the disease. Bacteriological analysis of the patient's prostatic secretion and semen samples revealed a chronic Enterococcus faecalis prostate infection, supporting a diagnosis of CBP. The patient's E. faecalis strain was resistant to several antibiotics and developed resistance to others during the course of treatment. Previous treatment with multiple courses of antibiotics, bacteriophages, probiotics, and immunologic stimulation had failed to achieve long term eradication of the infection or lasting mitigation of the symptoms. A cloned endolysin gene, encoded by E. faecalis bacteriophage ϕ Ef11, was expressed, and the resulting gene product was purified to electrophoretic homogeneity. A seven-day course of treatment with the endolysin resulted in the elimination of the E. faecalis infection to below culturally detectable levels, and the abatement of symptoms to near normal levels. Furthermore, during the endolysin treatment, the patient experienced no untoward reactions. The present report demonstrates the effectiveness of an endolysin as a novel modality in managing a recalcitrant infection that could not be controlled by conventional antibiotic therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stevens, Zhang, Kajsik, Płoski, Rydzanicz, Sabaka and Šutovský.)

Background: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment., Methods: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke's Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains., Results: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009-1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004-1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains., Conclusion: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late-onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid β42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25-0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61-1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4., (© 2020 John Wiley & Sons Ltd.)

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (-34%, p = .002) and young-trained individuals (-48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Objectives: Sleep disorders are frequent in stroke patients. The prevalence of sleep-disordered breathing (SDB), excessive daytime sleepiness (EDS), and restless legs syndrome (RLS) among stroke survivors is up to 91%, 72%, and 15%, respectively. Although the relationship between EDS and SDB is well described, there are insufficient data regarding the association of EDS with RLS. The aim of this study was to explore the association between EDS, SDB, and RLS in acute ischemic stroke., Methods: We enrolled 152 patients with acute ischemic stroke. Epworth Sleepiness Scale (ESS) was used to assess EDS. SDB was assessed using standard overnight polysomnography. All patients filled in a questionnaire focused on RLS. Clinical characteristics and medication were recorded on admission., Results: EDS was present in 16 (10.5%), SDB in 90 (59.2%) and RLS in 23 patients (15.1%). EDS was significantly more frequent in patients with RLS in comparison with the patients without RLS (26.1% versus 7.8%, P = .008). ESS was significantly higher in the population with RLS compared to the population without RLS (7 [0-14] versus 3 [0-12], P = .032). We failed to find any significant difference in the frequency of EDS and values of ESS in the population with SDB compared to the population without SDB. Presence of RLS (beta = 0.209; P = .009), diabetes mellitus (beta = 0.193; P = .023), and body mass index (beta = 0.171; P = .042) were the only independent variables significantly associated with ESS in multiple linear regression analysis., Conclusions: Our results suggest a significant association of ESS with RLS, diabetes mellitus, and obesity in patients with acute ischemic stroke., (© 2018 American Academy of Sleep Medicine)

Background: Autonomic dysfunction is a substantial part of extrapyramidal diseases, including Parkinson's disease (PD). Baroreflex is an important determinant of short-term blood pressure regulation and cardiovascular variability. Impaired baroreflex sensitivity (BRS) in PD has been a subject of investigation in several studies, however the relationship between BRS and orthostatic hypotension (OH) is still poorly understood., Objective: To compare the BRS of Parkinson's disease patients with those of an age-matched control population, and to determine BRS association with blood pressure, orthostatic hypotension and antiparkinson treatment., Patients and Methods: The study included 52 patients with Parkinson's disease and 52 controls. We assessed autonomic dysfunction with a Finometer device using the method of spontaneous fluctuations of blood pressure (BP) and the R-R interval in time domain, expressed as baroreflex sensitivity. Supine and standing blood pressure were measured under standard conditions., Results: BRS values were significantly lower in the PD group as compared to the control group: 4.0±2.0 vs. 6.4±3.8ms/mmHg (p=0.001). We determined a significant correlation between decreased BRS values and increased systolic BP (p=0.003) as well as between decreased BRS values and orthostatic hypotension (OH), in the PD group (p=0.048). Moreover, patients with PD and OH had significantly lower BRS as compared with patients with PD without OH (3.2±2 versus 4.5±2, p=0.045). We also determined that BRS values were significantly lower in the PD population treated with LDOPA+COMTI as compared to the LDOPA+COMTI untreated patients (3.0±1.5 vs. 4.8±2.0, p<0.001)., Conclusion: BRS was significantly lower in the PD group, supine hypertension and orthostatic hypotension was strongly associated with low BRS. We determined for the first time that orthostatic hypotension strongly correlates with decreased baroreflex sensitivity in PD patients. Moreover, orthostatic hypotension was associated with low BRS not only qualitatively but also quantitatively. We also revealed a strong association between LDOPA+COMTI therapy and decreased BRS in the literature for the first time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sleep-disordered breathing (SDB) is frequent in stroke patients. A strong association has been suggested between SDB and atrial fibrillation (AF). In this study, we evaluated the characteristics of SDB in etiologic subtypes of acute ischemic stroke. We also investigated the relationship between SDB and AF in acute ischemic stroke., Methods: We prospectively enrolled 72 patients with minor-to-moderate acute ischemic stroke. Clinical and laboratory characteristics of population were recorded on admission. SDB was assessed using standard polysomnography within 7 days after stroke onset., Results: Apnea-hypopnea index (AHI) in small-vessel strokes was significantly lower than that in large-artery atherosclerosis strokes (P = .031), cardioembolic strokes (P = .011), and strokes of other or unknown etiology (.008). Desaturation index (DI) in small-vessel strokes was significantly lower than that in cardioembolic strokes and in large-artery strokes (P = .008, P = .035). Arousal index (AI) in large-artery strokes was significantly higher than that in small-vessel strokes (P = .013), cardioembolic strokes (P = .007), and strokes of other or unknown etiology (.027). In a multivariate regression model were age (odds ratio [OR], 1.083; 95% confidence interval [CI], 1.022-1.148; P = .007) and DI (OR, 1.037; 95% CI, 1.004-1.071; P = .026) the only significant variables independently associated with AF., Conclusions: We observed higher AHI, DI, and AI in large-artery strokes that may relate to more severe neurologic deficit in this subgroup. Age and DI were the only independent variables significantly associated with AF in acute ischemic stroke. Higher AHI and DI in cardioembolic strokes may thus mirror more frequent premorbid presence of SDB in patients with AF., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)