Long-Term Oral Administration of Hyperimmune Egg-Based IgY-Rich Formulations Induces Mucosal Immune Response and Systemic Increases of Cytokines Involved in Th2- and Th17-Type Immune Responses in C57BL/6 Mice.

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

Early Detection of Inflammation and Malnutrition and Prediction of Acute Events in Hemodialysis Patients through PINI (Prognostic Inflammatory and Nutritional Index).

Protein-energy wasting and inflammation are major risk factors for complications in hemodialysis patients. As these risk factors are triggered by a pro-inflammatory state, oxidative stress and hemodynamic dysfunction, which overlap in hemodialyzed subjects, we aimed to assess the efficacy of a cost-effective and straightforward screening tool, the Prognostic Inflammatory and Nutritional Index (PINI), in regularly screening maintenance hemodialysis (MHD) patients, to detect early signs of inflammation and malnutrition. A 12-month follow-up was carried out on a cohort of 102 adult patients undergoing maintenance dialysis, during which the Prognostic Inflammatory and Nutritional Index (PINI) was calculated using the formula alpha1-Acid Glycoprotein (AGP) × C-reactive protein (CRP)/albumin (ALB) × transthyretin (TTR). A PINI score < 1 was considered normal. The patients were stratified based on their PINI score: 66 patients (64.70%) had a normal score, below 1, while 36 patients (35.30%) had a PINI score ≥ 1. Despite the absence of clinical evidence of inflammation at enrollment, the latter group exhibited higher levels of CRP. During the follow-up period, all patients with a PINI score ≥ 1 experienced at least one acute event, compared to only 6% of patients with a normal PINI score, which presented COVID-19 infection as an acute event. The evaluation of the PINI can effectively identify the silent malnutrition-inflammation syndrome and predict the risk of acute events. This straightforward test appears to be a rapid tool that is independent of the examiner's experience and subjectivity, thereby potentially reducing hospitalization costs.

Environmental and Metabolic Risk Factors Linked to Gallbladder Dysplasia.

Gallbladder disorders encompass a spectrum from congenital anomalies to inflammatory and neoplastic conditions, frequently requiring surgical intervention. Epithelial abnormalities like adenoma and metaplasia have the potential to progress to carcinoma, emphasizing the importance of histopathological assessment for early detection of malignancy. Gallbladder cancer (GBC) may be incidentally discovered during cholecystectomy for presumed benign conditions, underscoring the need for a thorough examination. However, the lack of clarity regarding the molecular mechanisms of GBC has impeded diagnostic and therapeutic advancements. Timely detection is crucial due to GBC's aggressive nature and poor prognosis. Chronic inflammation plays a central role in carcinogenesis, causing DNA damage and oncogenic alterations due to persistent insults. Inflammatory cytokines and microRNAs are among the various mediators contributing to this process. Gallbladder calcifications, particularly stippled ones, may signal malignancy and warrant preemptive removal. Molecular pathways involving mutations in oncogenes and tumor suppressor genes drive GBC pathogenesis, with proposed sequences such as gallstone-induced inflammation leading to carcinoma formation. Understanding these mechanisms, alongside evaluating mucin characteristics and gene mutations, can deepen comprehension of GBC's pathophysiology. This, in turn, facilitates the identification of high-risk individuals and the development of improved treatment strategies, ultimately enhancing patient outcomes. Thus, in this review, our aim has been to underscore the primary mechanisms underlying the development of gallbladder dysplasia and neoplasia.

Using 8-Hydroxy-2'-Deoxiguanosine (8-OHdG) as a Reliable Biomarker for Assessing Periodontal Disease Associated with Diabetes.

In recent years, research has shown that oxidative stress plays a significant role in chronic inflammatory conditions. The alteration of the oxidant/antioxidant balance leads to the appearance of free radicals, important molecules involved in both diabetes mellitus and periodontal disease. Diabetes is considered to be one of the major risk factors of periodontal disease and the inflammation characterizing this condition is associated with oxidative stress, implicitly resulting in oxidative damage to DNA. 8-Hydroxydeoxyguanosine (8-OHdG) is the most common stable product of oxidative DNA damage caused by reactive oxygen species, and its levels have been reported to increase in body fluids and tissues during inflammatory conditions. 8-OHdG emerges as a pivotal biomarker for assessing oxidative DNA damage, demonstrating its relevance across diverse health conditions, including neurodegenerative disorders, cancers, inflammatory conditions, and periodontal disease. Continued research in this field is crucial for developing more precise treatments and understanding the detailed link between oxidative stress and the progression of periodontitis. The use of the 8-OHdG biomarker in assessing and managing chronic periodontitis is an area of increased interest in dental research, with the potential to provide crucial information for diagnosis and treatment.

Atherosclerosis in Patients with Congenital Hemophilia: A Focus on Peripheral Artery Disease.

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy.

Cyclodextrins (CDs) are a family of carrier molecules used to improve the pharmacokinetic parameters of therapeutic molecules. These cyclic oligosaccharides have medical and pharmaceutical applications by being able to form inclusion complexes with molecules that are poorly soluble in water. The benefits of these complexes are directed towards improving the chemical and biological properties-i.e., solubility, bioavailability, stability, non-toxicity and shelf life of drug molecules. Since the 1960s, the first inclusion complexes used in therapeutics were those with α-, ß- and γ-CD, which proved their usefulness, but had certain degrees of particularly renal toxicity. Currently, to correct these deficiencies, ß-CD derivatives are most frequently used, such as sulfobutylether-ß-CD, hydroxypropyl-ß-CD, etc. Therefore, it is of interest to bring to the attention of those interested the diversity of current and potential future clinical applications of inclusion complexes in veterinary medicine and to present the contribution of these inclusion complexes in improving drug efficacy. The most important biological activities of ß-CD complexed molecules in the veterinary field are summarized in this short review.

The Role of the Prognostic Inflammatory and Nutritional Index (PINI) in the Evolution of Patients with Chronic Kidney Disease and Other Pathologies.

BACKGROUND: Protein-energy loss and inflammation are the main risk factors in the occurrence of complications in hemodialysis patients. The Prognostic Inflammatory and Nutritional Index (PINI) is a simple, inexpensive test to identify the early onset of inflammation and malnutrition in hemodialysis patients, critically ill subjects and those with malignancies. METHODS: A systemic review of English literature was conducted on the topic published between 1985 and 2022. A focused and sensitive search strategy was applied to the PUBMED database to identify relevant scientific articles in English. Once articles were identified, a detailed quality and bias assessment was performed. Two independent researchers analyzed the detailed data extraction. RESULTS: PINI proved to be a sensitive, powerful, low-cost and simple test. PINI has been useful in assessing evolution and prognostics in clinical care, with values above one being associated with a high risk of mortality and morbidity. It is useful in cases with surgical and postoperative complications, long hospitalization, as well as increased associated expenses. CONCLUSIONS: This is the first review of the literature on the above-mentioned topic (PINI) and is a valuable candidate for validating prognosis in patients with different pathologies.

Mitochondrial Dysfunction, Oxidative Stress, and Therapeutic Strategies in Diabetes, Obesity, and Cardiovascular Disease.

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis. Mitochondria are responsible for the majority of cellular ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, cellular aging, and cancer. In this article, we describe the pathophysiological changes in, and mitochondrial role of, metabolic disorders (diabetes, obesity, and cardiovascular disease) and their correlation with oxidative stress. We highlight the genetic changes identified at the mtDNA level. Additionally, we selected several representative biomarkers involved in oxidative stress and summarize the progress of therapeutic strategies.

The Role and Involvement of Stem Cells in Periodontology.

Periodontitis is a widespread inflammatory condition, characterized by a progressive deterioration of the supporting structures of the teeth. Due to the complexity of periodontal tissue and the surrounding inflammatory microenvironment, the repair of lesions at this level represents a continuous challenge. The regeneration of periodontal tissues is considered a promising strategy. Stem cells have remarkable properties, such as immunomodulatory potential, proliferation, migration, and multilineage differentiation. Thus, they can be used to repair tissue damage and reduce inflammation, potentially leading to periodontal regeneration. Among the stem cells used for periodontal regeneration, we studied dental mesenchymal stem cells (DMSCs), non-dental stem cells, and induced pluripotent stem cells (IPSCs). Although these cells have well documented important physiological characteristics, their use in contemporary practice to repair the affected periodontium is still a challenge.

Various Surgical Interventions in Treating Odontogenic Keratocyst: A Radiological Case Report.

The odontogenic keratocyst (OKC) is among the most aggressive odontogenic cysts because of its high recurrent rate. This study's objective was to describe a 7-year radiological and clinical follow-up of an OKC with two recurrences and a combination of surgical treatments. The cyst contents were drained at the biopsy to allow decompression, and then marsupialization (Partsch I) was carried out with good results. In the following two years, the endodontic and radiological evaluation of the neighboring teeth indicated endodontic avoidance. The remaining OKC enucleation (Partsch II) with chemical curettage and suture was performed two years after the first presentation, and the multifocal recurrences developed were also treated by enucleation and chemical curettage. At the last radiological follow-up, no recurrence was evident. Based on our experience, we concluded that patients diagnosed with a OKC should be radiologically evaluated at least once a year for at least 7 years, the endodontic diagnosis and treatment of neighboring teeth should be performed as early as possible, and the combination of surgical treatment and the long follow-up period is challenging.

The Effectiveness of Laser Applications and Photodynamic Therapy on Relevant Periodontal Pathogens (Aggregatibacter actinomycetemcomitans) Associated with Immunomodulating Anti-rheumatic Drugs.

Considering the current context of the increasing resistance of bacterial species to antibiotics and other antimicrobial agents, a major objective is to develop other antimicrobial approaches, which would be able to inactivate pathogens with considerable effectiveness. Two such methods are photodynamic disinfection therapy and laser irradiation. In view of the immunocompromised status of some patients under immunosuppressive therapy and potential drug interactions that can be established between systemic antimicrobial agents, the research of local, minimally invasive methods of inactivating periodontal pathogens in the context of these systemic therapies with modifying drugs of the immune response is justified. This in vitro study evaluated the antimicrobial action of a diode laser, wavelength 940 nm, and photodisinfection therapy at 670 nm (photosensitizer, 3,7 dimethyl phenothiazine chloride) on a type strain of Aggregatibacter actinomycetemcomitans, a known periodontal pathogen, in the presence and absence of active substances used in autoimmune disease therapy (Etanercept, Infliximab, Metothrexate). The association of a conventional antirheumatic drug with anti-TNF-α therapy determined a significantly greater inhibition of the strain of A. actinomycetemcomitans compared to monotherapy, in vitro. Photodisinfection caused a significant reduction in bacterial burden after a 30 s exposure in vitro, regardless of the pharmaceutical associations of biological and conventional disease-modifying antirheumatic drugs (DMARDs). Irradiation with a diode laser for 30 s at a power of 5 W caused a greater reduction compared to irradiation with 1 W. The application of laser and photodisinfection induced a significant reduction in Aggregatibacter actinomycetemcomitans in vitro and could be considered important adjunctive measures for the eradication of this oral pathogen in the context of immunomodulating therapy.

Cardiovascular Risk Factors in Patients with Congenital Hemophilia: A Focus on Hypertension.

Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.

Understanding the mechanisms of gallbladder lesions: A systematic review.

The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly invasive, and it is known that chronic inflammation of the gallbladder can lead to preneoplastic abnormalities and subsequently malignant phenotypes. Gallbladder neoplasia has a low incidence but is associated with a very poor prognosis. An early diagnosis is therefore extremely important in order to improve the prognosis of patients. Immunohistochemical markers of the mucin family can distinguish between different types of gallbladder lesions. Mucins are glycoproteins that can be attached to threonine residues that are O-glycosylated (due to the hydroxyl group of this amino acid). Mucins are divided into two types: those that bind to the membrane, such as MUC1, and those that form gels or are secreted, such as MUC5AC. Various alterations in mucin expression have been revealed to be associated with the development of neoplasia, as they modulate cell growth, karyokinetic transformation, dedifferentiation, adhesion, invasion and immune surveillance. p53 is a tumor suppressor gene and is linked to the development of different types of neoplasia. The incidence of the p53 gene is variable in the pathophysiology of gallbladder cancer. Several studies have revealed an incidence of ~50% of the p53 gene in gallbladder tumors. Studying the immunohistochemical profile of mucins and the presence of different gene mutations in neoplastic lesions of the gallbladder and surrounding mucosa may contribute to the understanding of the pathophysiology of the disease and the mechanisms involved in tumor development, allowing the identification of patients at increased risk of developing neoplasia, thus leading to improved management.

H-FABP Levels and Psycho-Emotional Improvement of CABG Patients during Cardiac Rehabilitation.

(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and anxiety. Comprehensive cardiac rehabilitation is, therefore, essential to both physical and psychological recovery. (2) Methods: This is a unicentric, prospective study on 120 consecutive post-CABG patients undergoing a 6-month cardiac rehabilitation program based on physical exercise, Mediterranean diet principles, and Q10 coenzyme antioxidant supplements. H-FABP levels, depression, and anxiety scores (Hamilton HAM-D and HAM-A scales) were monitored after surgery and at 6 months. (3) Results: Mean H-FABP dropped from 60.56 to 4.81. Physical ability increased from 1-2 to 4-5 METS. Mean depression and anxiety improved from 15.88 to 6.96 and from 25.13 to 15.68, respectively. Median scores went down 50% for depression and 9% for anxiety. Explored associations between H-FABP and psycho-emotional status were statistically insignificant. (4) Conclusions: patients adhered to the program and improved significantly in all studied aspects. Clinical significance is discussed in the context of countries like Romania, where such programs are limited by systemic and financial constraints. Further research directions are identified.

Mycobacterium tuberculosis and Pulmonary Rehabilitation: From Novel Pharmacotherapeutic Approaches to Management of Post-Tuberculosis Sequelae.

Tuberculosis (TB) is still a worldwide public health burden, as more than 1.3 million deaths are expected to be reported in 2021. Even though almost 20 million patients have completed specific anti-TB treatment and survived in 2020, little information is known regarding their pulmonary sequelae, quality of life, and their need to follow rehabilitation services as researchers shifted towards proper diagnosis and treatment rather than analyzing post-disease development. Understanding the underlying immunologic and pathogenic mechanisms during mycobacterial infection, which have been incompletely elucidated until now, and the development of novel anti-TB agents could lead to the proper application of rehabilitation care, as TB sequelae result from interaction between the host and Mycobacterium tuberculosis. This review addresses the importance of host immune responses in TB and novel potential anti-TB drugs' mechanisms, as well as the assessment of risk factors for post-TB disease and usefulness of guidance and optimization of pulmonary rehabilitation. The use of rehabilitation programs for patients who successfully completed anti-tuberculotic treatment represents a potent multifaceted measure in preventing the increase of mortality rates, as researchers conclude that a patient with a TB diagnosis, even when properly completing pharmacotherapy, is threatened by a potential life loss of 4 years, in comparison to healthy individuals. Dissemination of pulmonary rehabilitation services and constant actualization of protocols could strengthen management of post-TB disease among under-resourced individuals.

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania.

PURPOSE: The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD). METHODS: We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations. RESULTS: 350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 > 220 ng/mL was a predictor of cardiovascular events, while the EF < 50% was a predictor for renal outcomes. For CKD patients with PCSK9 > 220 ng/mL and hsCRP > 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers. CONCLUSION: The results of this study show that PCSK9 > 220 ng/mL was predictor for cardiovascular events, while EF < 50% was predictor for CKD progression to ESRD. PCSK9 > 220 ng/mL and hsCRP > 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

Correlations between Salivary Immuno-Biochemical Markers and HbA1c in Type 2 Diabetes Subjects before and after Dental Extraction.

Dental extraction can trigger certain sequences of complex processes that involve both hard (alveolar bone) and soft tissue (periodontal ligament, gingiva) remodeling. Type 2 diabetes is a serious risk factor for many oral pathologies, both in terms of progression and severity, but also regarding subsequent rehabilitation possibilities. The aim of this study was to establish whether certain molecules: osteoprotegerin (OPG), kappa B nuclear factor receptor activator ligand (RANKL), hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α), interleukin 18 (IL-18), matrix metalloproteinase 9 (MMP-9) and oxidative stress markers-total oxidant status (TOS), total antioxidant capacity (TAC)-evaluated in saliva are modified post-extraction in type 2 diabetes mellitus subjects and whether there is a correlation with HbA1c levels. The aforementioned markers plus HbA1c were investigated in a group of systemically healthy subjects (n = 45) and in a type 2 diabetes mellitus group (n = 41) before and three months after a tooth extraction. Diabetes patients' recorded increased levels of OPG, RANKL, TNF-α, MMP-9, IL-18 and TOS compared to controls both pre- and post-extraction. In both study groups, the average OPG, HGF and TAC level recorded an upward trend three months post-extraction. TNF-α registered a statistically significant decrease only in the diabetes group after dental extraction, together with a decrement of mean HbA1c levels in the diabetes group. By plotting the ROC (receiver operating characteristic) curve, at baseline RANKL, TNF-α, IL-18, MMP-9, TOS and OPG were good predictors of HbA1c levels. Post-extraction, there was a significant correlation between HbA1c and oxidative status biomarkers, however the linear regression model indicated the influence of all studied salivary markers in HbA1c determinism, in a considerable proportion. In conclusion, our study demonstrated that several oxidative status markers and proinflammatory biomarkers are modified in the saliva of diabetic patients and they correlate to HbA1c levels, thus being potential indicators of the post-extraction healing status in the oral cavity.

Experimental EDX analysis of different periodontal splinting systems.

Physiological/normal tooth mobility may be defined as the slight displacement of the clinical crown of a tooth, which is allowed by the resilience of an intact and healthy periodontium, under the application of a moderate force. The factors influencing the success and longevity of dental splinting are the type of material used for the splint, the type of composite resin, the number and location of the dental units included for splinting (maxillary or mandibular arch). In periodontology, the term 'splint' is defined as the joining of two or more teeth into a rigid unit through restorations or fixed or removable devices. The purpose of using periodontal splints for tooth immobilization is to provide a period of rest in the areas where the healing process has begun and to allow normal functioning there where the tissues alone would not be able to withstand occlusal forces. The aim of the present study was to evaluate comparatively, by means of energy dispersive electron spectrometry (EDX), the chemical composition in the case of in vitro samples that structurally reproduce direct periodontal immobilization systems using fiberglass strips and fluid composite resins. The differences in the chemical composition of the investigated materials can influence their physiochemical properties, but also their biological and toxicological reliability. Elements such as C, O, Al, Si and Ba were identified as common elements among the resins tested in the present study. The only difference in terms of the component elements was found in the case of the fluid composite Clearfil Majesty ES Flow, which, apart from the elements mentioned, also presented Co in its structure.

Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania.

This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C > G, c.502G > A, c.1618G > A mutations in exon 2, exon 4, exon 11, and exon 13-15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations.

Evaluation of Oxidative Stress before and after Using Laser and Photoactivation Therapy as Adjuvant of Non-Surgical Periodontal Treatment in Patients with Rheumatoid Arthritis.

(1) Background: The aim of this split-mouth design study was to analyze the clinical periodontal indexes and oxidative stress markers in gingival crevicular fluid modifications after three periodontal disease treatment possibilities (scaling and root planning-SRP; SRP and diode laser-L; SRP and photodynamic therapy-PDT). (2) Methods: The study was conducted on 52 patients: systemically healthy subjects with periodontal disease-non-RA (n = 26); and test group (n = 26) subjects with rheumatoid arthritis and periodontal disease-RA. Clinical periodontal measurements (probing depth-PD; Löe and Silness gingival index-GI; papillary bleeding index-PBI; and periodontal community index of treatment needs-CPITN) and oxidative stress markers (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4 hydroxynonenal (4-HNE)) were analyzed at baseline (T0), after three sessions of periodontal treatment (T1), and 6 months after treatment (T2). (3) Results: Periodontal therapy improved clinical periodontal measurements and oxidative stress markers in both analyzed groups, with supplementary benefits for laser- and PDT-treated periodontal pockets. (4) Conclusions: The analyzed oxidative stress markers decreased significantly following non-surgical periodontal therapy in both rheumatoid arthritis and systemically healthy patients. All the periodontal disease treatment possibilities analyzed in this study offered clinical and paraclinical improvements; however, the association of laser with SRP and photodisinfection with SRP yielded the best clinical and paraclinical outcomes when compared to SRP alone.