Lichen Planus of the Lip-Case Series and Review of the Literature.

Background and Objectives: Lichen planus of the lip (LPL) is a chronic inflammatory condition that resembles actinic cheilitis, discoid lupus erythematosus, graft-versus-host disease, and lichenoid reaction to dental materials or drugs. The purpose of this study was to conduct a literature review on lichen planus lip involvement and to report a retrospective observational study that characterises and explores the clinical, histopathological, and evolution of the lesions in a group of patients with unique involvement of LPL. Materials and Methods: Clinical data of patients diagnosed with LPL was retrieved from the medical charts of the patients referred to the Oral Pathology Department of the "Carol Davila" University of Medicine and Pharmacy. A concurrent electronic literature research was carried out using PubMed and Web of Science from 2003 to 2023. Results: Eleven patients diagnosed with unique LPL were analysed (male/female ratio was 1.75, mean age 63.64 years ± 12.52). All patients presented lesions of the lower lip; the clinical forms were atrophic (six cases) and erosive (five cases), and the histopathological exam confirmed the diagnosis. After topical treatment with corticosteroids, most of the patients had complete remission. The literature review revealed 24 studies (sixteen case reports and eight case series) which comprised 84 patients. Isolated lip involvement was reported in 17 studies, and five articles with concomitant oral lichen planus, while two articles did not mention this criterion. Conclusions: Our study brings new data on isolated lichen planus of the lip that primarily affects the lower lip with predominance in male patients. It was reported worldwide in patients between 22 and 75 years old. Topical corticosteroids were the main treatment prescribed and they usually brought remission of the lesions. Lichen planus of the lip is a challenging diagnosis for oral health practitioner providers as well as for dermatologists.

Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience.

Background: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. Methods: We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Results: Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect (p = 0.016, p < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. Conclusions: The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.

Impact of Altered Lipid Profile in Oral Lichen Planus.

Background:Oral lichen planus (OLP) is a chronic inflammatory disease that affects the oral mucosa. This disorder has been suggested to be related to an impairment of lipid metabolism and profile. A number of studies indicate a higher incidence of dyslipidemia in OLP patients compared to not-affected individuals. Objectives: The aim of this study was to investigate the correlations between lipid profile alterations and clinical features of oral lichen planus. Patients and methods:A total of 52 patients diagnosed with OLP were enrolled in this study. Data regarding the demography, symptoms, severity of lesions assesed by Thongprasom score and lipid profile status were collected from the medical charts. The study group was divided into two sub-cohorts: Group 1, which included OLP patients with lipid profile within the normal range, and Group 2 comprising OLP patients with alterations of the lipid status. Results:The comparative analysis between the two groups found a statistically significant association between the lipid profile and OLP symptoms. Thus, the most frequent symptom was pain, in OLP patients with normal lipid status (Group 1), and burning, in those with altered lipid status (Group 2) (p=0.050). Moreover, the presence of symptoms was reported by a higher percentage of patients from Group 2 (75%) than Group 1 (68.25%). Patients reporting burning symptomatology showed higher triglyceride levels than those who reported pain (p=0.032). Furthermore, we found that male OLP patients have higher levels of LDL compared with female subjects (p=0.021). Conclusion:Lipid profile changes are not associated with an increased severity of OLP lesions. A statistically significant association was found between burning sensation and higher lipid profile parameters.

Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics.

Introduction: Mild cognitive impairment (MCI) can progress to Alzheimer's disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI. Methods: In this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies. Results: Fifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points). Conclusion: The results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05029765].

Retrospective Study from a Single Center in Romania of 347 Renal Transplant Patients Treated with Tacrolimus, Mycophenolate, and Steroids to Evaluate the Association Between Anti-HLA Antibodies and 5-Year Graft Survival.

BACKGROUND Kidney transplantation is the most recommended treatment in chronic kidney disease. The recipient's immune system reacts to a kidney graft as to an alloantigen by producing antibodies (anti-human leukocyte antigens [HLAs]). Although immunosuppressive therapy is used to overcome this problem, the long-term survival of a kidney graft after 5 years remains low. This retrospective study from a single center in Romania of 347 renal transplant patients treated with tacrolimus, mycophenolate, and steroids aimed to evaluate the association between anti-HLA antibodies and 5-year graft survival. MATERIAL AND METHODS Anti-HLA antibodies were screened and identified using the Luminex method, while tacrolimus levels were monitored using the chemiluminescent assay. RESULTS Twenty-seven patients had pre-existing anti-HLA antibodies, while 320 patients did not. Of the 320 patients, 15% developed anti-HLA antibodies following kidney transplantation. The intrapatient minimum blood level of tacrolimus (cut-off value: 4.6 ng/mL) after transplantation was significantly associated with the risk of de novo anti-HLA antibodies (P<0.001). In patients with or without de novo anti-HLA antibodies, the 5-year allograft survival rate was 77.1% vs 90.8% (P=0.004). After Bonferroni correction, donor age (P=0.001), and donor type (P<0.0001) were statistically associated with the risk of allograft rejection. CONCLUSIONS This study showed that anti-HLA antibodies at 5 years after kidney transplantation were significantly associated with graft failure. The findings support previous studies and indicate that monitoring of anti-HLA antibodies should be considered in patients with renal transplant.

Biological senescence risk score. A practical tool to predict biological senescence status.

BACKGROUND: Ageing and biological senescence, both related to cardiovascular disease, are mediated by oxidative stress and inflammation. We aim to develop a predictive tool to evaluate the degree of biological senescence in coronary patients. METHODS: Relative telomere length (RTL) of 1002 coronary patients from the CORDIOPREV study (NCT00924937) was determined at baseline in addition to markers of inflammatory response (hs-C-Reactive Protein, monocyte chemoattractant protein-1, IL-6, IL-1ß, TNF-α, adiponectin, resistin and leptin) and oxidative stress (nitric oxide, lipid peroxidation products, carbonylated proteins, catalase, total glutathione, reduced glutathione, oxidized glutathione, superoxide dismutase and peroxidated glutathione). Biological senescence was defined using the cut-off value defined by the lower quintile of relative telomere length in our population (RTL = 0.7629). We generated and tested different predictive models based on logistic regression analysis to identify biological senescence. Three models were designed to be used with different sets of information. RESULTS: We selected those patients with all the variables proposed to develop the predictive models (n = 353). Statistically significant differences between both groups (Biological senescence vs. Nonbiological senescence) were found for total cholesterol, catalase, superoxide dismutase, IL-1ß, resistin and leptin. The area under the curve of receiver-operating characteristic to predict biological senescence for our models was 0.65, 0.75 and 0.72. CONCLUSIONS: These predictive models allow us to calculate the degree of biological senescence in coronary patients, identifying a subgroup of patients at higher risk and who may require more intensive treatment.

Gut microbiota and aging-A focus on centenarians.

Gut microbiota (GM) is a dynamic organ throughout the lifespan. Aging is a complex process that comprises a plethora of mechanisms such as senescence, immunosenescence and inflammaging, representing important pathways of age-related diseases. GM structure could both influence and be influenced by aging occurring changes within the host. A unique category of long living individuals exists, namely centenarians that have the outstanding capacity to adapt to various challenges. Longevity seems to be associated with certain GM which, among other factors, might render individuals more resistant to age-related diseases and subsequently to long living. Diet, prebiotics, probiotics and synbiotics may contribute to longevity through GM modulating. Currently, the exact mechanisms of the association between GM and the host in relation with extended lifespan remain unknown and should be further investigated.

Long-term dietary adherence and changes in dietary intake in coronary patients after intervention with a Mediterranean diet or a low-fat diet: the CORDIOPREV randomized trial.

PURPOSE: Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. METHODS: 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. RESULTS: From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. CONCLUSIONS: A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Effects of Aging and Diet on Cardioprotection and Cardiometabolic Risk Markers.

The prevalence of several diseases increases by age, including cardiovascular diseases, which are the leading cause of morbidity and mortality worldwide. Aging, as a complex process characterized by senescence, triggers various pathways, such as oxidative stress, systemic inflammation, metabolism dysfunction, telomere shortening, mitochondrial dysfunction and deregulated autophagy. A better understanding of the mechanisms underlying senescence may lead to the development of new therapeutic targets and strategies for age-related pathologies and extend the healthy lifespan. Modulating lifestyle risk factors and adopting healthy dietary patterns remain significant tools in delaying the aging process, decreasing age-associated comorbidities and mortality, increasing life expectancy and consequently, preventing the development of cardiovascular disease. Furthermore, such a strategy represents the most cost-effective approach, and the quality of life of the subjects may be significantly improved. An integrated, personalized approach targeting cardiometabolic aging and frailty is suggested in daily clinical practice. However, it should be initiated from an early age. Moreover, there is a need for further well designed and controlled studies in order to elucidate a link between the time of feeding, longevity and cardiovascular prevention. In the future, it is expected that the pharmacological treatment in cardioprotective management will be necessary, accompanied by equally important lifestyle interventions and adjunctive exercise.

Gut Microbiota, Obesity and Bariatric Surgery: Current Knowledge and Future Perspectives.

BACKGROUND: There is an urgent need for a better understanding and management of obesity and obesity- associated diseases. It is known that obesity is associated with structural and functional changes in the microbiome. METHODS: The purpose of this review is to present current evidence from animal and human studies, demonstrating the effects and the potential efficacy of microbiota modulation in improving obesity and associated metabolic dysfunctions. RESULTS: This review discusses possible mechanisms linking gut microbiota dysbiosis and obesity, since there is a dual interaction between the two of them. Furthermore, comments on bariatric surgery, as a favourable model to understand the underlying metabolic and inflammatory effects, as well as its association with changes in the composition of the gut microbiota, are included. Also, a possible impact of anti-obesity drugs and the novel antidiabetic drugs on the gut microbiota has been briefly discussed. CONCLUSION: More research is needed to better understand here discussed the association between microbiota modulation and obesity. It is expected that research in this field, in the following years, will lead to a personalized therapeutic approach considering the patient's microbiome, and also give rise to the discovery of new drugs and/or the combination therapies for the management of obesity and obesity-related co-morbidities.

Low Intake of Vitamin E Accelerates Cellular Aging in Patients With Established Cardiovascular Disease: The CORDIOPREV Study.

Leukocyte telomere length (LTL) shortening is a biomarker of cellular aging that can be decelerated by diet. We aimed to investigate the effect of dietary intake of vitamin E on biomarkers of cellular senescence in patients with established cardiovascular disease. To this end, DNA from 1,002 participants of the CORDIOPREV study (NCT00924937) was isolated and LTL was measured by real-time PCR. Dietary information was collected using a 146-item food frequency questionnaire, and several oxidative stress and damage biomarkers were determined. We found that patients with an inadequate intake of vitamin E according to the European Food Safety Authority, U.S. Food and Nutrition Board, and Spanish dietary recommendation had shorter LTL than those with an adequate intake (p = .004, p = .015, and p = .005, respectively). Moreover, we observed a positive correlation between olive oil, fish consumption and LTL (r2 = .083, p = .010; r2 = .090, p = .006, respectively). Subjects who consumed more than 30 mL olive oil/day had longer LTL than subjects with lower consumption (p = .013). Furthermore, we observed higher glutathione peroxidase activity in subjects consuming less vitamin E (p = .031). Our findings support the importance of an adequate consumption of the antioxidant vitamin E, and the value of the diet as a modulating tool of the senescence process.

Telomerase RNA Component Genetic Variants Interact With the Mediterranean Diet Modifying the Inflammatory Status and its Relationship With Aging: CORDIOPREV Study.

Background: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients. Methods: Inflammation status (high-sensitivity C-reactive protein [hsCRP], glucose metabolism-glucose, insulin, and glycated hemoglobin [HbA1c], and homeostasis model assessment of insulin resistance [HOMA-IR]), LTL, FAs, and single nucleotide polymorphisms (SNPs) of the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002 patients from the CORDIOPREV study (NCT00924937). Results: We report an interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA) affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among individuals with MUFA levels above the median, CC individuals showed higher LTL and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a greater decrease in hsCRP than G-allele carriers. These results were not adjusted for multiple statistical testing and p less than .05 was considered significant. Conclusions: Our findings suggest that the TERC rs12696304 SNP interacts with MUFA improving inflammation status and telomere attrition related with CHD. Moreover, the MedDiet intervention improves the inflammatory profile in CC individuals compared with the G-allele carriers. These interactions could provide a right strategy for personalized nutrition in CHD patients.

Eyesight quality and Computer Vision Syndrome.

The aim of the study was to analyze the effects that gadgets have on eyesight quality. A prospective observational study was conducted from January to July 2016, on 60 people who were divided into two groups: Group 1 - 30 middle school pupils with a mean age of 11.9 ± 1.86 and Group 2 - 30 patients evaluated in the Ophthalmology Clinic, "Sf. Spiridon" Hospital, Iași, with a mean age of 21.36 ± 7.16 years. The clinical parameters observed were the following: visual acuity (VA), objective refraction, binocular vision (BV), fusional amplitude (FA), Schirmer's test. A questionnaire was also distributed, which contained 8 questions that highlighted the gadget's impact on the eyesight. The use of different gadgets, such as computer, laptops, mobile phones or other displays become part of our everyday life and people experience a variety of ocular symptoms or vision problems related to these. Computer Vision Syndrome (CVS) represents a group of visual and extraocular symptoms associated with sustained use of visual display terminals. Headache, blurred vision, and ocular congestion are the most frequent manifestations determined by the long time use of gadgets. Mobile phones and laptops are the most frequently used gadgets. People who use gadgets for a long time have a sustained effort for accommodation. A small amount of refractive errors (especially myopic shift) was objectively recorded by various studies on near work. Dry eye syndrome could also be identified, and an improvement of visual comfort could be observed after the instillation of artificial tears drops. Computer Vision Syndrome is still under-diagnosed, and people should be made aware of the bad effects the prolonged use of gadgets has on eyesight.

TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study.

BACKGROUND: Several single nucleotide polymorphisms have been proposed as potential predictors of the development of age-related diseases. OBJECTIVE: To explore whether Tumor Necrosis Factor Alpha (TNFA) gene variants were associated with inflammatory status, thus facilitating the rate of telomere shortening and its relation to cellular aging in a population with established cardiovascular disease from the CORDIOPREV study (NCT00924937). MATERIALS AND METHODS: SNPs (rs1800629 and rs1799964) located at the TNFA gene were genotyped by OpenArray platform in 840 subjects with established cardiovascular disease. Relative telomere length was determined by real time PCR and plasma levels of C-reactive protein by ELISA. In a subgroup of 90 subjects, the gene expression profiles of TNFA, IKKß, p47phox, p40phox, p22phox and gp91phox were determined by qRT-PCR. RESULTS: GG subjects for the SNP rs1800629 at the TNFA gene showed shorter relative telomere length and higher plasma levels of hs-CRP than A-allele subjects (p<0.05). Consistent with these findings, the expression of pro-inflammatory (TNFA) and pro-oxidant (p47phox and the gp91phox) genes was higher in GG subjects than A allele subjects (p<0.05). CONCLUSION: Subjects carrying the GG genotype for the SNP rs1800629 at the TNFA gene show a greater activation of the proinflammatory status than A-allele carriers, which is related to ROS formation. These ROS could induce DNA damage especially in the telomeric sequence, by decreasing the telomere length and inducing cellular aging. This effect may also increase the risk of the development of age-related diseases.