Discriminant Potential of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in Greek Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment.

Background: Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer's disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer's disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). Objective: The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Methods: Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Results: Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. Conclusions: The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.

Knowledge, familiarity, and impact of the COVID-19 pandemic on barriers to seeking mental health services among older people: a cross-sectional study.

AIM: The COVID-19 pandemic caused drastic changes in older people's daily activities with a negative impact on their mental health, yet older people are less likely to seek mental health services. This study aims to explore the relationship between knowledge of and familiarity with mental health services, along with the impact of the COVID-19 pandemic, and barriers to seeking mental health services among older people. METHODS: A descriptive cross-sectional study was conducted with a convenience sample of 352 older people, recruited among community-dwelling adults who attended randomly selected postal offices and pension outlets. Three tools were used: a structured interview schedule for sociodemographic and clinical characteristics of older people, the revised version of the Knowledge and Familiarity of Mental Health Services Scale (KFFMHS-R), and the Barriers to Mental Health Services Scale Revised (BMHSS-R). RESULTS: All participants reported experiencing mental health distress during the COVID-19 pandemic. Intrinsic barriers had a higher mean score than extrinsic barriers, and 27.4% of the variance of overall barriers to seeking mental health could be explained through regression analysis by familiarity, knowledge of mental health services, and age. Overall barriers explained 24.4% of the variance of older people's perceived distress as an impact of the COVID-19 pandemic (F = 22.160, P < 0.001). CONCLUSIONS: Knowledge of mental health services was the most significant predictor of barriers to seeking mental health services during the COVID-19 pandemic. Higher barriers predicted higher distress as an impact of the COVID-19 pandemic. The results of the study suggest the need for a multidisciplinary mental health team for older people.

The linkage between prevalence of integron I and reduced susceptibility to biocides in MDR Klebsiella pneumoniae isolated from neonates.

Background and Objectives: Klebsiella pneumoniae causes challenging nosocomial fatal infections including neonatal sepsis. Our study aims at clarifying the contribution of integrons in the observed reduced susceptibility of multidrug-resistant (MDR) K. pneumoniae isolated from septicemic neonates to the clinically used antimicrobial agents and biocides. Materials and Methods: Eighty-six K. pneumoniae isolates were collected from Mansoura University Children's Hospital from septicemic neonates. Isolates were subjected to antibiotic and biocide susceptibility using disk diffusion and the agar dilution method, respectively. The distribution of different classes of integrons was screened in the isolates by PCR. Detected inegron I was sequenced in selected isolates. Results: Fifty-seven isolates (66.27%) were MDR. In the MDR isolates, class I integron was detected in 23 (40.3%), integron III was detected in 20 (35%), whereas integron II could not be detected. Sequencing results of integron I from MDR K. pneumoniae isolates revealed that only aminoglycoside and folate synthesis inhibitors gene cassettes were detected, while the rest of the resistance genes were not associated with integron I. Conclusion: The presence of integron I in MDR K. pneumoniae tested isolates may contribute only to some biocide resistance, however, it does not seem to be the only contributor in multiple drug resistance.

A small fragment of factor B as a potential inhibitor of complement alternative pathway activity.

BACKGROUND: The complement system is a key player in innate immunity and a modulator of the adaptive immune system. Among the three pathways of complement, the alternative pathway (AP) accounts for most of the complement activation. Factor B (FB) is a major protease of the AP, making it a promising target to inhibit the AP activity in conditions of uncontrolled complement activation. METHODS: Based on the data obtained from sequence analysis and conformational changes associated with FB, we expressed and purified a recombinant FB fragment (FBfr). We tested the inhibitory activity of the protein against the AP by in vitro assays. RESULTS: FBfr protein was proven to inhibit the complement AP activity when tested by C3b deposition assay and rabbit erythrocyte hemolytic assay. CONCLUSION: Our recombinant FBfr was able to compete with the native human FB, which allowed it to inhibit the AP activity. This novel compound is a good candidate for further characterization and testing to be used in complement diagnostic tests and as a drug lead in the field of complement therapeutics.

Middle East Treatment Strategies and Clinical Outcomes in Patients with Atrial Fibrillation: One-Year Follow-up Data from Garfield-AF Study.

INTRODUCTION: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) aims to determine real-life treatment patterns and clinical outcomes of patients with newly diagnosed non-valvular atrial fibrillation (AF) and at least one investigator-determined risk factor for stroke. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalized ratio fluctuations; and (3) therapy compliance and persistence patterns. METHODS: Evolution in baseline treatment for patients enrolled in sequential cohorts showed an increase in prescribing of novel oral anticoagulants over time. Variability in novel oral anticoagulant prescription is primarily due to differences in availability of treatment and prescribing habits between countries and care settings. The GARFIELD-AF registry also provides insights into clinical management and related outcomes of AF in Middle East populations. RESULTS: A total of 1660 patients with non-valvular AF (median age 64.0 years, interquartile range 56.0-72.0), mostly diagnosed in cardiology settings from Egypt, the United Arab Emirates and Turkey, were recruited in cohorts 3-5. Data from patient populations in the Middle East related to the rates of stroke/systemic embolism, major bleeding and all-cause mortality 1 year after diagnosis of AF and treatment strategies, based on the stroke and bleeding risk, have been analysed and compared with the rest of the world. The use of antithrombotic treatment in the Middle East was generally higher than the non-Middle East, with increased prescription of antiplatelet therapy (AP) therapy. Appropriate use of Factor Xa inhibitors/direct thrombin inhibitors (DTIs) were 74.4% and Factor Xa/DTI + APs were 70.4% in the overall population, whereas they were 57.1% and 63.6%, respectively, in the Middle East. CONCLUSION: We have found that rates of stroke and bleeding were lower, although mortality was higher, in the Middle East population. This paper describes the baseline characteristics, patterns of antithrombotic treatment and 1-year outcomes in Middle East AF patients. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Identifier, NCT01090362.

Dasatinib mitigates renal fibrosis in a rat model of UUO via inhibition of Src/STAT-3/NF-κB signaling.

This research aimed to investigate the reno-protective impact of the tyrosine kinase inhibitor dasatinib (DAS) against renal fibrosis induced by unilateral ureteral obstruction (UUO) in rats. DAS administration improved renal function and mitigated renal oxidative stress with paralleled reduction in the ligated kidney mass index, significant retraction in renal histopathological alterations and suppression of renal interstitial fibrosis. Nevertheless, DAS administration attenuated renal expression of phosphorylated Src (p-Src), Abelson (c-Abl) tyrosine kinases, nuclear factor-kappaB (NF-κB) p65, and phosphorylated signal transducer and activator of transcription-3 (p-STAT-3)/STAT-3 with paralleled reduction in renal contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1). DAS diminished interstitial macrophage infiltration and decreased renal profibrotic transforming growth factor-ß1 (TGF-ß1) levels and suppressed interstitial expression of renal α-smooth muscle actin (α-SMA) and fibronectin. Collectively, DAS slowed the progression of renal interstitial fibrosis, possibly via attenuating renal oxidative stress, impairing Src/STAT-3/NF-κB signaling, and reducing renal inflammation.

Usability of a self-administered geriatric assessment mHealth: Cross-sectional study in a geriatric clinic.

AIM: mHealth can facilitate comprehensive geriatric assessment (CGA) in countries with limited geriatric healthcare facilities. It can compensate for the lack of trained geriatricians and integrate CGA in different healthcare disciplines leading to better clinical outcomes. This study assessed the usability of a self-administered geriatric assessment smartphone application. METHODS: A cross-sectional study included participants from the geriatric clinic at Ain Shams University Hospital, Cairo, Egypt. This study was performed in three phases: development and validation of an abbreviated geriatric assessment tool, and validation of the application prototype. Twenty subjects were recruited for pretesting the abbreviated assessment tool, then another 50 patients to validate this tool in a face-to-face interview. Afterwards, another 12 patients completed the prototype followed by a standardized office visit interview. Each assessment domain was evaluated in agreement with a valid reference test during the clinical interview. RESULTS: The application was simple and user friendly. The scores of each domain correlated to the reference test scores (rho = 0.59-0.93). Most of the domains exhibited good agreement with the reference tests (kappa = 0.68-1.00) (except for frailty and nutritional assessment). CONCLUSIONS: The mHealth geriatric assessment is possible and highly desirable during physical distancing and beyond. Obviously, this approach cannot substitute for clinical examination and multidisciplinary standard CGA. However, it may overcome some barriers facing the geriatrization of medicine. It would help general practitioners to provide pre-CGA evaluation, particularly in areas with limited access to formal geriatric healthcare services. Geriatr Gerontol Int 2021; 21: 222-228.

Predictors of NOAC versus VKA use for stroke prevention in patients with newly diagnosed atrial fibrillation: Results from GARFIELD-AF.

INTRODUCTION: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. METHODS: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ±â€¯antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. RESULTS: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. CONCLUSION: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.

Optical and electrical properties of all-inorganic Cs2AgBiBr6 double perovskite single crystals.

In this work, we explored the possibility of using Cs2AgBiBr6, a double perovskite crystal, for radiation detection. Cs2AgBiBr6 crystals were grown using the solution growth technique. The resistivity of the as-grown Cs2AgBiBr6 crystal is larger than 1010 Ω cm, which is high enough to ensure low leakage current for fabrication of semiconductor radiation detectors. Using the temperature-dependent resistivity measurements, we estimated that the Fermi level is at 0.788 eV above the valence band and the material is a p-type semiconductor. From the low-temperature cathodoluminescence measurements, two near band gap energies at 1.917 eV and 2.054 eV were revealed.

Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats.

Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of coptis. Liver fibrosis is a worldwide health problem with no established therapy until now. The aim of our study is to investigate the efficacy of BBR on hepatic fibrosis induced in rats and to uncover other mechanisms. Rats were injected with thioacetamide (TAA) (200 mg/kg, i.p) twice per week for 6 weeks to induce fibrosis. Treated groups were gavaged with BBR (50 mg/kg/day, p.o) simultaneously with TAA injection. Hepatic antioxidant enzymes (catalase, SOD, GPx) were assessed in hepatic homogenate. Their activities were attenuated by TAA injection and elevated by BBR administration. Additionally, serum IL-6 and mRNA levels of IL-1ß, IL-6, IL-10 and IFN-γ were evaluated as inflammatory markers. Our results showed that BBR suppressed the inflammation induced by TAA injection. Tissue expression of α-SMA (marker of activated HSCs), TGF-ß1 and fibronectin were measured by immunohistochemistry as well as mRNA expressions of TGF-ß1 and fibronectin were quantified as fibrotic markers. The collagen deposition in hepatic tissues was assessed by Masson's trichome staining. BBR significantly alleviated TGF-ß1 production, decreased collagen and fibronectin deposition and consequently attenuated hepatic fibrogenesis. Akt pathway controls cell survival, proliferation, migration and adhesion. The relative phosphorylation of Akt was determined in hepatic homogenates that was increased with TAA injection and decreased by BBR treatment. Inhibition of Akt pathway has been linked to the intrinsic pathway of apoptosis. Caspase-3, caspase-9, Bcl-2 and Bax were quantified as apoptotic markers using qPCR and also caspase-3 by immunohistochemistry. BBR-treated rats showed an increase in the expression of apoptotic markers. Moreover, BBR-treated rats showed restoration of normal liver lobular architecture as shown by H&E staining. In conclusion, BBR is a potential therapeutic candidate for liver fibrosis owing to its antioxidant and anti-inflammatory activities.

Naringin attenuates thioacetamide-induced liver fibrosis in rats through modulation of the PI3K/Akt pathway.

AIMS: Naringin (NR) is a flavanone glycoside extracted from grapefruits and citrus fruits. The aim of this study is to investigate the antifibrotic efficacy of NR in thioacetamide (TAA)-induced hepatic fibrosis in rats through evaluating NR effect on the PI3K/Akt pathway. MAIN METHODS: Hepatic fibrosis was induced in rats by intraperitoneal injection of TAA (200mg/kg) twice per week for 6weeks. Simultaneously, NR (40mg/kg/day, p.o.) was given along with TAA injection. The ratio of P-Akt/Akt was assessed in hepatic homogenate as well as antioxidant enzymes (catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx)) and lipid peroxidation marker, malondialdehyde (MDA). Serum level of interleukin (IL)-6 were measured using ELISA. Hepatic tissues were examined histopathologically using hematoxylin and eosin (H&E) and Masson trichome staining. Tissue expression of alpha smooth muscle actin (α-SMA), transforming growth factor ß1 (TGF-ß1), caspase-3 and fibronectin were scored immunohistochemically. Finally, the mRNA level of cytokine genes (IL-1ß, IL-6, IL-10, interferon gamma (IFN-γ)), caspase-3, TGF-ß1 and fibronectin were quantified using qPCR. KEY FINDINGS: NR significantly suppressed Akt phosphorylation associated with increased number of caspase-3 positive cells especially in the fibrotic areas. Liver tissues of treated rats showed restoration of normal liver histology and decrease in collagen and fibronectin deposition. Furthermore, NR treatment ameliorated oxidative stress and inflammatory cytokine production. SIGNIFICANCE: NR alleviated experimental liver fibrosis through inhibition of PI3K/Akt pathway beside its anti-inflammatory and antioxidant effects. Therefore, NR is a promising therapeutic candidate for hepatic fibrosis.

Complement-Coagulation Cross-Talk: A Potential Mediator of the Physiological Activation of Complement by Low pH.

The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration, and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example, renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross-talk between the contact system (intrinsic pathway) and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD) accompanied by metabolic acidosis, in which therapeutic alkalinization of urine has been shown significantly to reduce tubular complement activation products, an effect, which may have important implications for slowing progression of CKD.

Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa remains one of the major clinical pathogens that burden immuno-compromised patients and patients with cystic fibrosis. The present study aimed to define the role of the lectin pathway of complement in the immune-defence against P. aeruginosa in a mouse model of invasive pneumonia. Using in vitro assays specific for each of the three complement pathways, we demonstrate that some strains of P. aeruginosa bind lectin pathway recognition sub-components and initiate complement activation in a lectin pathway-specific mode. All of the tested strains activated complement via classical and alternative pathways. We assessed the importance of lectin pathway activation in fighting P. aeruginosa infections by testing a lectin pathway activating strain in a mouse model of intra-nasal infection. MASP-2 (mannan binding lectin associated serine protease-2) deficient mice, which have no lectin pathway activity, had no significant survival disadvantage compared to wild type littermates (72.7% and 81.8% survival, respectively, p=0.48). Likewise, no difference in opsonising activity was seen between MASP-2 sufficient and MASP-2 deficient mouse sera. Moreover, cytokine expression profiles in the lungs of WT mice and MASP-2-/- mice were similar throughout the course of P. aeruginosa infection. We conclude that the lectin pathway does not play an essential role in fighting P. aeruginosa infection in mice.