Role of Angiotensin Receptor Blockers in the context of Alzheimer’s Disease

alexandrossfakianakis shared this article with you from Inoreader Role of Angiotensin Receptor Blockers in the context of Alzheimer's Disease via Fundamental & Clinical Pharmacology Abstract As the world's population ages, the prevalence of age-related neurological disorders such as Alzheimer's disease (AD) is increasing. There is currently no treatment for Alzheimer's disease, and the few approved medications have a low success rate in lowering symptoms. As a result, several attempts are underway worldwide to identify new targets for the therapy of Alzheimer's disease. In pre-clinical studies of Alzheimer's disease, it was recently found that inhibition of angiotensin-converting enzyme (ACE) and blocking of the angiotensin II receptors reduce symptoms of neurodegeneration, Aβ plaque development, and tau hyperphosphorylation. Angiotensin II type I (AT1) blockers, such as telmisartan, candesartan, valsartan, and others, have a wide safety margin and are commonly used to treat hypertension. Renal and cardiovascular failure are reduced due to their vascular protective actions. Inhibition of AT1 receptors in the brain has a neuroprotective impact in humans, reducing the risk of stroke, increasing cognition, and slowing the progression of Alzheimer's disease. The review focuses on the mechanisms via which AT1 blockers may act beneficially in Alzheimer's disease. Although their effect is evident in pre-clinical studies, clinical trials, on the other hand, are in short supply to validate the strategy. More dose-response experiments with possible AT1 blockers and brain-targeted administration will be needed in the future. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Banter in psychotherapy: Relationship to treatment type, therapeutic alliance, and therapy outcome

alexandrossfakianakis shared this article with you from Inoreader Banter in psychotherapy: Relationship to treatment type, therapeutic alliance, and therapy outcome via Journal of Clinical Psychology Abstract Introduction The use of humor in psychotherapy is widely considered to improve therapy outcomes and typically depends on context, patient sensitivity, and the therapist's humor style. Different types of humor may impact treatment type, therapeutic alliance, and therapy outcome; however, evidence from psychotherapy sessions on the role of banter has been sparse to date. Therefore, the study aims to examine banter in a secondary analysis of psychotherapy sessions. Method The sample consisted of 68 depressed outpatients treated with one of three treatment types: psychoanalytic therapy (PA), psychodynamic therapy (PD), and cognitive-behavioral therapy (CBT). Banter and therapeutic alliance were rated for therapy sessions taken from the middle phase of treatment, outcome was assessed at the end of treatment. Results The main findings were (1) clinical examples of banter in psychotherapy were found in 62 from 68 sessions, (2) significantly more bantering in the main bantering category of facilitation for CBT sessions as compared to other treatment types, (3) facilitative banter as a significant predictor for the positive introject, (4) a significant correlation between bantering and bond between therapist and client. Furthermore, based on these results, psychometric properties of the Klagenfurt Bantering Instrument (KBI) are reported. Conclusion From a bantering perspective, this study emphasizes the need to consider session context, client response, and sarcastic markers when categorizing negative banter using the KBI. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prediction and validation of microbial community function from normal pulp to pulpitis caused by deep dentinal caries

alexandrossfakianakis shared this article with you from Inoreader Prediction and validation of microbial community function from normal pulp to pulpitis caused by deep dentinal caries via International Endodontic Journal Abstract Introduction Microbial function changes may be responsible for dental pulp transformation from normal to diseased. However, studies on the prediction and verification of the function of the microbial community in the deep dentine and pulp of caries-induced pulpitis are lacking. Methods This study included 171 cases of deep dentinal caries divided into normal pulp (NP), reversible pulpitis (RP), and irreversible pulpitis (IRP). In Experiment I, the microbial-community composition was identified in 111 samples using 16S ribosomal DNA. Function prediction was performed through phylogenetic investigation of communities by PICRUSt prediction and qPCR. In Experiment II, different microbiome functions were confirmed in 60 samples using liquid chromatography-tandem mass spectrometry. Results In Experiment I, microbial abundance significantly differed in the IRP group compared to the other two groups. The RP and NP groups had the same microbiome composition, but the predicted functional difference between the RP and NP groups pertained to membrane transport (P<0.010). The predicted functional difference between the IRP and NP groups pertained to amino-acid, co-factor, and vitamin metabolism (P<0.010). In Experiment II, Kyoto Encyclopedia of Genes and Genomes functional annotation revealed that the differential metabolites between the RP and NP groups did not participate in membrane transport; however, the differential metabolites between the IRP and NP groups participated in amino-acid metabolism. Conclusions The near-pulp microbiome in RP and NP with deep dentinal caries had the same differential function. However, amino acid metabolism in near the pulp microbial community differed between IRP and NP with deep dentinal caries. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Office‐Based Treatment of Vocal Fold Polyps and Reinke's Edema: A Rational Comparison With Suspension Laryngoscopy

alexandrossfakianakis shared this article with you from Inoreader Office‐Based Treatment of Vocal Fold Polyps and Reinke's Edema: A Rational Comparison With Suspension Laryngoscopy via The Laryngoscope Benign laryngeal lesions have traditionally been treated surgically through suspension laryngoscopy. In the present study, we report comparable vocal results with an office-based transnasal endoscopic approach with a fiber laser capable of providing favorable morbidity and reduced operation times. Objective Benign laryngeal lesions have traditionally been treated through suspension laryngoscopy under general anesthesia (GA). Recently, the development of operative videoendoscopes coupled with photoangiolytic lasers has allowed clinicians to treat these conditions in the outpatient clinic. We report our experience in the office-based (OB) setting for the treatment of patients affected by vocal fold polyps (VFPs) and Reinke's edema (RE), comparing it to patients treated under GA. Methods A retrospective analysis was conducted on patients affected by VFP or RE. A 445 nm diode blue laser was used through the operative channel of a flexible video-endoscope for OB procedures, while GA surgeries were carried out with cold steel instrumentation. The Voice Handicap Index-10 (VHI-10) represented the primary outcome. Endoscopic outcomes, duration, and morbidity of the procedures were investigated as secondary outcomes. Results A total of 153 patients were retrospectively enrolled. 52 were treated in an OB setting, while 91 underwent GA. Regarding patients with RE, both the OB and GA cohorts showed a significant improvement in VHI-10 (from 12.7 to 2.6 and 19.5 to 5.1, respectively; p < 0.001), as did those with VFPs (from 11.8 to 2.3 and 15.9 to 2.9 respectively; p < 0.001). No differences were found when comparing VHI-10 in the OB and GA cohorts. The mean procedural time of OB treatment (4.9 min) was significantly shorter than GA (37.1 min). No adverse events were reported. Conclusion Our data demonstrate the efficacy and safety of the OB setting. For selected patients, OB treatments offer comparable vocal outcomes, favorable morbidity, and reduced operation times, making them an appealing alternative to the traditional approach. Level of Evidence 3 Laryngoscope, 2023 View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection

alexandrossfakianakis shared this article with you from Inoreader A real‐world exploratory study on the feasibility of vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection in special populations with penicillin allergy or failed in previous amoxicillin‐containing therapies via Helicobacter Abstract Background The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin. Objective To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies. Design Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing. Results A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline. Conclusions For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus

alexandrossfakianakis shared this article with you from Inoreader Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractCholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3β4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and β4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of chol... View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction

alexandrossfakianakis shared this article with you from Inoreader Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction via Helicobacter Abstract Objectives To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF). Methods PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR. Results One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54–5.37) and the West (OR, 4.03; 95% CI: 2.59–6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26–3.63), not in the West (OR, 0.80; 95% CI: 0.61–1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08–7.64) and 3.86 (95% CI: 2.69–5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78–12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West. Conclusions Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Periodontitis and low cognitive performance: A population‐based study

alexandrossfakianakis shared this article with you from Inoreader Periodontitis and low cognitive performance: A population‐based study via Journal of Clinical Periodontology Abstract Aim To study the epidemiological association between periodontitis and low cognitive performance amongst older adults, within a representative sample of the US population. Materials and methods Data from 2086 older adults (≥60 years old), representative of 77.1 million people, were retrieved from the NHANES 2011–2014 database. Periodontitis cases were identified and classified according to the AAP/CDC criteria (mild, moderate, and severe). Cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's disease (CERAD), the Animal Fluency (AFT), the Digit Symbol Substitution (DSST) tests, and the global cognition score. The lowest non-survey weighted quartile for each cognitive test was defined as low cognitive performance. Simple and multiple regression analyses were performed. Results Moderate and severe periodontitis were significantly associated with a low DSST performance (OR = 1.66, and OR = 2.97, respectively). Each millimeter of increase in mean CAL was associated with a lower AFT (OR = 1.44), DSST (OR = 1.86), and global cognition (OR = 1.50) performance. Conclusions The findings of the present study suggest the presence of an independent association between periodontitis and low cognitive performance amongst older adults (≥60 years old). This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats.

alexandrossfakianakis shared this article with you from Inoreader Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats. via Journal of Clinical Periodontology ABSTRACT Aim To explore the potential mechanisms of neuroinflammation (microglia, blood-brain barrier [BBB] permeability, and the sphingosine-1-phosphate [S1P] pathways) resulting from the association between periodontitis and depression in rats. Materials and methods This pre-clinical in vivo experimental study used Wistar rats, in which experimental periodontitis (P) was induced by using oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum. Then a chronic mild stress (CMS) model was implemented to induce depressive-like behavior, resulting in four groups: P with CMS (P+CMS+), P without CMS (P+CMS-), CMS without P (P-CMS+), and controls (P-CMS-). After harvesting brain samples, Protein/mRNA expression analyses and fluorescence immunohistochemistry were performed in the frontal cortex (FC). Results were analyzed by ANOVA tests. Results CMS exposure increased the number of microglia (an indicator of neuroinflammation) in the FC. In the combined model (P+CMS+), there was a decrease in the expression of tight junction proteins (zonula occludens-1 [ZO-1], occludin) and an increase in intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1) and matrix metalloproteinase 9 (MMP9), suggesting a more severe disruption of the BBB. The enzymes and receptors of S1P were also differentially regulated. Conclusions Microglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Initial supplementary dose of dolutegravir in second-line antiretroviral therapy: a non-comparative, double-blind, randomised placebo-controlled trial

alexandrossfakianakis shared this article with you from Inoreader Initial supplementary dose of dolutegravir in second-line antiretroviral therapy: a non-comparative, double-blind, randomised placebo-controlled trial via Clinical Infectious Diseases Advance Access Abstract Background Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice daily dolutegravir dosing when co-administered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed HIV-1 RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofov ir-emtricitabine-efavirenz (TEE). Methods We conducted a randomised, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (two consecutive HIV-1 RNA≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA<50 copies/mL at week 24. This study was not powered to compare arms. Results 130 participants were randomised (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and two were lost to follow-up. At week 24, 55/64 (86%, 95% confidence interval [CI], 75–93%) in the supplementary dolutegravir arm and 53/65 (82%, 95% CI, 70–90%) in the placebo arm had HIV-1 RNA<50 copies/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of six participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance. Conclusions Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.