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Evidence of Clinical Efficacy and Pharmacological Mechanisms of Resveratrol in the Treatment of Alzheimer’s Disease

Curr Alzheimer Res. 2023 Dec 1. doi: 10.2174/0115672050272577231120060909. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the efficacy and pharmacological mechanisms of resveratrol in Alzheimer’s disease (AD) patients.

METHODS: We conducted a thorough exploration of existing randomized controlled trials concerning the treatment of Alzheimer’s disease patients using resveratrol, utilizing accessible open databases. Quantitative variables were represented as a standardized mean difference (SMD), accompanied by a 95% confidence interval (CI). Additionally, we examined the potential targets and plausible pathways associated with the impact of resveratrol on Alzheimer’s disease using network pharmacology techniques.

RESULTS: Our meta-analysis comprised five trials involving 271 AD patients, of whom 139 received resveratrol treatment and 132 received placebo treatment. Compared with placebo therapy, resveratrol treatment resulted in a significant improvement in Alzheimer’s Disease Cooperative Study- Activities of Daily Living (ADAS-ADL) scores (SMD=0.51; 95% CI, 0.24 to 0.78) and cerebrospinal fluid (CSF) Aβ40 (SMD=0.84; 95% CI, 0.21 to 1.47) and plasma Aβ40 levels (SMD=0.43; 95% CI, 0.07 to 0.79). However, the improvement in the resveratrol-treated group compared with the placebo treatment group on the Mini-Mental State Examination (MMSE) score, CSF Aβ42 and plasma Aβ42 levels, and brain volume was not significant. There were no noteworthy statistical variances in the occurrence of adverse effects noted between the two groups. The outcomes of network pharmacology divulged that the principal enriched interaction pathway between resveratrol and Alzheimer’s disease is primarily concentrated within the PI3K signaling pathways. Resveratrol’s potential key targets for the treatment of AD include MAKP1, HRAS, EGFR, and MAPK2K1.

CONCLUSION: While having a high safety profile, resveratrol has efficacy in AD patients to a certain extent, and more data are required to validate the efficacy of resveratrol for the treatment of AD in the future. Suppression of the PI3K signaling pathways could hold significant importance in the treatment of AD patients using resveratrol.

PMID:38047366 | DOI:10.2174/0115672050272577231120060909

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Physeal Migration During Knee-guided Growth With Tension Band Plates: Influence of Implant Position

J Pediatr Orthop. 2023 Dec 4. doi: 10.1097/BPO.0000000000002583. Online ahead of print.

ABSTRACT

OBJECTIVE: Physeal migration during guided growth with tension band plates (TBPs) has been poorly described. The positioning factors associated with this phenomenon and its clinical implications are unknown. Our aim is to determine the influence of implant position on the risk of physeal migration during knee-guided growth with TBP.

METHODS: Retrospective study of 491 patients who underwent temporary hemi or epiphysiodesis with TBP around the knee between 2007 and 2019. We identified 29 patients who presented physeal migration during follow-up. Demographic and clinical data were collected, and the following measures were obtained from the immediate postoperative radiographs: epiphyseal screw base-physis distance/epiphyseal screw tip-physis distance, interscrew angle, epiphyseal screw-physis angle(ES-PHa)/metaphyseal screw-physis angle, plate-physis angle, epiphyseal screw-plate angle/metaphyseal screw-plate angle, and epiphyseal screw-physis length ratio. Using follow-up radiographs, the type of physeal migration of the epiphyseal screw (touch, occupy, or traverse) and the status of the physis after implant removal (unaltered, physeal bar, and skeletal maturity) were also recorded. A descriptive analysis of the cases and a case-control comparison of imaging studies were performed.

RESULTS: The median patient age at intervention was 12.2 years (interquartile range: 11.3 to 14.1), and 76% were males. A statistically significant difference between cases and controls was obtained for epiphyseal screw base-physis distance (3.7 vs 6.3; P = 0.029), epiphyseal screw tip-physis distance (3.6 vs 7.85; P = 0.002), ES-PHa (-0.1 vs 7.45; P = 0.007), and plate-physis angle (85.45 vs 88.60; P = 0.012). In a categorical analysis, a significant difference was found for the ES-PHa categories (P = 0.002) and for the ES-PHa/metaphyseal screw-physis angle categorical pair (P = 0.018). In 16, 17, and 12 cases the physis was touched, occupied, or traversed, respectively, although we found no physeal alterations after plate removal.

CONCLUSIONS: In our study, physeal migration of TBP is not an uncommon phenomenon, although no physeal abnormalities were detected. Convergent placement of the epiphyseal screw with the base or tip close to the physis should be avoided as this position is associated with a higher risk of physeal migration.

LEVEL OF EVIDENCE: Level III-case-control study.

PMID:38047324 | DOI:10.1097/BPO.0000000000002583

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Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling

Am J Physiol Regul Integr Comp Physiol. 2023 Dec 4. doi: 10.1152/ajpregu.00164.2023. Online ahead of print.

ABSTRACT

Down syndrome (Ds) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of Ds, to quantify heart structure and function with echocardiography in 18-month male Ts65Dn and WT mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of Ds. The left ventricle was smaller in Ts65Dn vs WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end-systole (mm2), left ventricular area end-diastole (mm2), left ventricular diameter end-systole (mm), left ventricular diameter end-diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (bpm), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn vs. WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for Ds.

PMID:38047317 | DOI:10.1152/ajpregu.00164.2023

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Key correlates of exclusive breastfeeding at three timepoints: Evidence from Ethiopia

Reprod Female Child Health. 2022 Dec;1(2):99-110. doi: 10.1002/rfc2.15. Epub 2022 Sep 14.

ABSTRACT

AIM: To compare factors associated with exclusive breastfeeding (EBF) within 1 h of birth, within 3 days, and within the first 6 months post-birth.

METHODS: We used multivariate logistic regression models and data from “The Alive and Thrive Phase 2 Amhara Baseline Survey 2015” from Ethiopia (N = 3113).

RESULTS: Giving colostrum was strongly associated with EBF at all three time points, controlling for multiple confounders. Putting the baby to the breast before cleaning the baby and before cleaning the mother was significantly associated with EBF within 1 h and for the first 3 days. EBF within an hour of birth was more likely for girl babies than boy babies. Having a healthcare professional check whether the baby was sucking well was significantly associated with EBF 3 days post-birth.

CONCLUSIONS: The World Health Organization recommends breastfeeding within 1 h of birth and exclusively thereafter for 6 months, which can improve health outcomes for infants and children. In Ethiopia, many factors influence breastfeeding practices, but little is known about how these factors differ at various key timepoints in the 6 months after birth. Our study provides important information on correlates of EBF at three timepoints and shows that factors that are significantly correlated with EBF vary over time. Future research should assess the potential causal links among statistically significant associations between EBF and risk factors at various times between birth and 6 months of age. Ultimately, these findings have the potential to inform areas of intervention related to promoting EBF.

PMID:38047292 | PMC:PMC10691011 | DOI:10.1002/rfc2.15

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Brand Experience and Customer Loyalty in Dentistry: The Role of Perceived Brand Authenticity

Int J Dent. 2023 Nov 24;2023:2541243. doi: 10.1155/2023/2541243. eCollection 2023.

ABSTRACT

This study investigates the impact of brand experience (BE) on customer loyalty (CL) and examines the possible mediating effect of brand authenticity (BA) and the moderating effect of frequency of visits on the original relationship between BE and CL in dental practices. A descriptive, deductive, and quantitative research methodology was applied, with a self-administrated survey questionnaire over a cross-sectional convenience sample from dental clinics and centers in Erbil, Sulaymaniyah, and Duhok (Iraqi Kurdistan). Data were collected in July and August 2022. SPSS AMOS 26 was used for analyzing 952 patients’ responses. The results indicate that BE has a statistically significant positive effect on CL. However, only affective experiences, cognitive experiences, and behavioral experiences have a statistically positive effect on CL. BA has a significant direct mediation effect on the original relationship between BE and CL. In addition, a greater frequency of dental visits improves the BE and impacts CL. Discussion, recommendations, and future research orientation are provided.

PMID:38047272 | PMC:PMC10691884 | DOI:10.1155/2023/2541243

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SNG100, a novel topical treatment for moderate atopic dermatitis, in patients aged 6 years or older: A randomised, double-blind, active-controlled trial

Skin Health Dis. 2023 Oct 14;3(6):e293. doi: 10.1002/ski2.293. eCollection 2023 Dec.

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are efficient but associated with side effects. Novel topical treatments with a favourable safety profile are needed. SNG100 is a novel composition of hydrocortisone 1% in a cream base comprising sulphated polysaccharide (SPS; extracted from in-house cultivated Porphyridium Cruentum unicellular algae), a well-known hydrating, moisturising and a skin barrier repairing agent.

OBJECTIVES: To assess the safety, usability and efficacy of SNG100 cream in patients aged ≥6 years with moderate AD.

METHODS: In this proof of concept phase I, double-blind, randomised trial, participants received one of three treatments for 14 days: SNG100 twice daily (BID), hydrocortisone 1% BID or mometasone furoate once daily (QD). The primary endpoint was the safety and tolerability of SNG100 cream compared to hydrocortisone 1% and mometasone furoate. The secondary endpoint was the subject’s usability of SNG100. Exploratory efficacy endpoints included percent change from baseline in SCOring AD (SCORAD), Eczema Area and Severity Index, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, pruritus Numerical Rating Score (NRS), peak pruritus-NRS and Investigator’s Global Assessment. Subjects were also followed up without any treatment for additional 14 days.

RESULTS: Overall, 66 participants were screened, and 60 patients were randomised. SNG100 demonstrated a high safety profile, similar to marketed products hydrocortisone 1% and mometasone furoate 0.1%, with no unanticipated drug safety related events. SNG100 and mometasone furoate 0.1% cream achieved almost similar and statistically significant greater percentage reductions from baseline in SCORAD as compared to hydrocortisone 1% cream. SNG100 demonstrated significant improvement in NRS as compared to hydrocortisone 1% cream. Remarkably, SNG100 led to a lasting effect with only 29.4% of subjects returning to IGA3 during the follow-up period compared to 50% and 38.9% in the hydrocortisone 1% and in mometasone furoate treatment arms, respectively.

CONCLUSIONS: Topical SNG100 is an effective, safe, and well-tolerated innovative treatment for moderate AD. Trial registration number: NCT04615962 (Topical Cream SNG100 for Treatment in Moderate AD Subjects).

PMID:38047249 | PMC:PMC10690700 | DOI:10.1002/ski2.293

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Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer

Adv Radiat Oncol. 2023 May 6;8(6):101266. doi: 10.1016/j.adro.2023.101266. eCollection 2023 Nov-Dec.

ABSTRACT

PURPOSE: Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival.

METHODS AND MATERIALS: Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy.

RESULTS: Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P = .006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P = .008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P = .006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables.

CONCLUSIONS: Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

PMID:38047228 | PMC:PMC10692286 | DOI:10.1016/j.adro.2023.101266

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Factors Affecting Prostate Displacement During Volumetric Modulated Arc Therapy in Prone Position After High-Dose-Rate Brachytherapy for Prostate Cancer

Adv Radiat Oncol. 2023 May 29;8(6):101277. doi: 10.1016/j.adro.2023.101277. eCollection 2023 Nov-Dec.

ABSTRACT

PURPOSE: In irradiating the prostate and pelvic lymph node regions, registration based on bony structures matches the pelvic lymph node regions but not necessarily the prostate position, and it is important to identify factors that influence prostate displacement. Therefore, we investigated factors influencing prostate displacement during volumetric modulated arc therapy after single-fraction high-dose-rate brachytherapy (HDR-BT) for prostate cancer and the trends in displacement for each fraction.

METHODS AND MATERIALS: Seventy patients who underwent pelvic volumetric modulated arc therapy of 46 Gy in the prone position 15 days after 13 Gy HDR-BT were included. Prostate displacement relative to bony structures was calculated using cone beam computed tomography. Systematic error (SE) and random error (RE) were evaluated in the right-left (RL), craniocaudal (CC), and anteroposterior (AP) directions. The association with clinical and anatomic factors on the planning computed tomography or magnetic resonance imaging was analyzed. Prostate volume change (PVC) was defined as the volume change at 2 days after HDR-BT. Displacement trends were individually examined from the first to 23rd fractions.

RESULTS: The mean SE in the RL, CC, and AP directions was -0.01 mm, -2.34 mm, and -0.47 mm, respectively. The root mean square of the RE in the RL, CC, and AP directions was 0.44 mm, 1.14 mm, and 1.10 mm, respectively. SE in the CC direction was independently associated with bladder volume (P = .021, t statistic = 2.352) and PVC (P < .001, t statistic = -8.526). SE in the AP direction was independently associated with bladder volume (P = .013, t statistic = -2.553), PVC (P < .001, t statistic = 5.477), and rectal mean area (P = .008, t statistic = 2.743). RE in the CC direction was independently associated with smoking (P = .035). RE in the AP direction was associated with PVC (P = .043). Gradual displacement caudally and posteriorly occurred during the irradiation period.

CONCLUSIONS: Anatomic characteristics of the bladder, rectum, and prostate predict SE. Smoking and PVC predict RE. In particular, whether PVC is ≥140% affects setting internal margins.

PMID:38047223 | PMC:PMC10692303 | DOI:10.1016/j.adro.2023.101277

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Unanticipated Radiation Replanning for Stage III Non-small Cell Lung Cancer

Adv Radiat Oncol. 2023 May 27;8(6):101275. doi: 10.1016/j.adro.2023.101275. eCollection 2023 Nov-Dec.

ABSTRACT

PURPOSE: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC).

METHODS AND MATERIALS: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning.

RESULTS: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28).

CONCLUSIONS: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

PMID:38047222 | PMC:PMC10692281 | DOI:10.1016/j.adro.2023.101275

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Prevalence of Oral Potentially Malignant Disorders among Fishermen Population in and around Pondicherry, South India – A Cross Sectional Study

Indian J Occup Environ Med. 2023 Jul-Sep;27(3):226-228. doi: 10.4103/ijoem.ijoem_255_22. Epub 2023 Jul 14.

ABSTRACT

CONTEXT: In India fishing is a traditional occupation second only to agriculture. Fishermen are a marginalized group with high levels of occupational stress predisposing them to develop addictions to tobacco, alcohol, and areca nut chewing. These habits are well-established causes of developing oral potentially malignant disorders and oral cancer.

AIMS: To determine the prevalence of oral potentially malignant disorders among the fishermen population in and around Pondicherry.

SETTINGS AND DESIGN: Cross-sectional study.

METHODS AND MATERIAL: A descriptive cross-sectional study was conducted using a pre-designed and pre-tested questionnaire to assess the prevalence of oral potentially malignant disorders among the fishermen population in and around Pondicherry.

STATISTICAL ANALYSIS USED: Descriptive statistics were used with Pearson’s correlation.

RESULTS: The study showed 24.8% of fishermen consumed tobacco, and 7.3% consumed both tobacco and alcohol. Oral potentially malignant disorders were seen in 16.79% of the population.

CONCLUSIONS: The fishermen had a higher rate of addictions to tobacco, alcohol, and areca nut chewing and a higher prevalence of oral potentially malignant disorders.

PMID:38047179 | PMC:PMC10691522 | DOI:10.4103/ijoem.ijoem_255_22