Effect of lead exposure on histone modifications: A review.

Lead at any levels can result in detrimental health effects affecting various organ systems. These systematic manifestations under Pb exposure and the underlying probable pathophysiological mechanisms have not been elucidated completely. With advancements in molecular research under Pb exposure, epigenetics is one of the emerging field that has opened many possibilities for appreciating the role of Pb exposure in modulating gene expression profiles. In terms of epigenetic alterations reported in Pb toxicity, DNA methylation, and microRNA alterations are extensively explored in both experimental and epidemiological studies, however, the understanding of histone modifications under Pb exposure is still in its infant stage limited to experimental models. In this review, we aim to present a synoptic view of histone modifications explored in relation to Pb exposure attempting to bring out this potential lacunae in research. The scarcity of studies associating histone modifications with Pb toxicity, and the paucity of their validation in human cohort further emphasizes the strong research potential of this field. We summarize the review by presenting our hypotheses regarding the involvement of these histone modification in various diseases modalities associated with Pb toxicity.

Comparative outcomes of systemic diseases in people with type 2 diabetes, or obesity alone treated with and without GLP-1 receptor agonists: a retrospective cohort study from the Global Collaborative Network : Author list.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored. OBJECTIVE: This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity. METHODS: We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers. RESULTS: In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001). CONCLUSIONS: GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms.

Genetic Patterns of Oral Cavity Microbiome in Patients with Sickle Cell Disease.

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus, followed by Fusobacterium nucleatum, Prevotella, and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa, Prevotella scoposa, and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius, Actinomyces graevenitzii, Actinomyces odontolyticus, and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora's constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.

The Molecular Comorbidity Network of Periodontal Disease.

Periodontal disease, a multifactorial inflammatory condition affecting the supporting structures of the teeth, has been increasingly recognized for its association with various systemic diseases. Understanding the molecular comorbidities of periodontal disease is crucial for elucidating shared pathogenic mechanisms and potential therapeutic targets. In this study, we conducted comprehensive literature and biological database mining by utilizing DisGeNET2R for extracting gene-disease associations, Romin for integrating and modeling molecular interaction networks, and Rentrez R libraries for accessing and retrieving relevant information from NCBI databases. This integrative bioinformatics approach enabled us to systematically identify diseases sharing associated genes, proteins, or molecular pathways with periodontitis. Our analysis revealed significant molecular overlaps between periodontal disease and several systemic conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and inflammatory bowel diseases. Shared molecular mechanisms implicated in the pathogenesis of these diseases and periodontitis encompassed dysregulation of inflammatory mediators, immune response pathways, oxidative stress pathways, and alterations in the extracellular matrix. Furthermore, network analysis unveiled the key hub genes and proteins (such as TNF, IL6, PTGS2, IL10, NOS3, IL1B, VEGFA, BCL2, STAT3, LEP and TP53) that play pivotal roles in the crosstalk between periodontal disease and its comorbidities, offering potential targets for therapeutic intervention. Insights gained from this integrative approach shed light on the intricate interplay between periodontal health and systemic well-being, emphasizing the importance of interdisciplinary collaboration in developing personalized treatment strategies for patients with periodontal disease and associated comorbidities.

Pulp stones in unerupted teeth: a retrospective analysis using cone-beam computed tomography.

BACKGROUND: A pulp stone is a calcified mass that develops in the dental pulp of any tooth. Despite many studies examining the relationship between pulp stone formation and non-oral factors, the methods used in these studies have been unable to explain the exact role of these factors alone as distinct from probable effects within the oral cavity environment. Considering that totally unerupted (impacted or developing) teeth are unexposed to the oral cavity's environmental and functional conditions, they provide a more suitable material for studying the effects of these non-oral factors on pulp stone formation. This research study aimed to investigate pulp stones in unerupted teeth and the associated factors in a Saudi subpopulation. METHODS: The study included 644 cone-beam computed tomography images, with 496 (50.9%) maxillary and 479 (49.1%) mandibular teeth. Of the investigated patients, 293 (45.5%) were men, and 351 (54.5%) were women. The age range was 15-76 years. A chi-square test was used to investigate the associations between pulp stones and age, gender, and history of systemic disease and chronic medication use. RESULTS: Pulp stones in unerupted teeth were present in 24.2% of the examined dental jaws and 18.6% of the examined teeth. There was no statistically significant relationship between pulp stones and gender (p > 0.05). A significantly greater percentage of pulp stones were found with increasing age (p = 0.000). Additionally, a significantly increased number of pulp stones was observed in patients with systemic diseases and chronic medications (p < 0.05). CONCLUSIONS: The results support the idea that pulp stones can be present in any type of unerupted tooth. This study provides additional evidence of the increased incidence of pulp stones with age, systemic disease, and chronic medications.

The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Oral and Gut Microbiota Dysbiosis Due to Periodontitis: Systemic Implications and Links to Gastrointestinal Cancer: A Narrative Review.

Periodontitis can disrupt oral and gut microbiota, leading to dysbiosis that affects overall systemic health. Besides the spread of periodontal pathogens by the hematogenous route, they can also be translocated into the gastrointestinal tract, possibly intervening in the neoplastic process in the gastrointestinal tract. This manuscript reviews the relationship between oral and gut microbiota due to periodontitis, discussing systemic health implications and potential links to gastrointestinal cancer. This article highlights the significance and effect of dysbiosis in the gut, emphasizing the importance of maintaining oral health to prevent systemic diseases. Lastly, it will go through therapeutic innovations such as probiotics and oral microbiota analysis tools for systemic disease detection. These findings will mark the integration of oral health management in clinical practice to lower systemic disease risk and improve overall patient outcomes. Aim of work: This manuscript aims to unravel the pathological interaction between oral and gut microbiota and their bidirectional effect on systemic diseases. Materials and methods: The review was performed using the MEDLINE and ScienceDirect databases. Reviewed articles were published in English between the year 2015 and 2024. The search used keywords such as ("oral microbiota" AND "periodontal disease") OR ("oral microbiota" AND "gastrointestinal cancer") OR ("Porphyromonas gingivalis" AND "periodontal disease") OR ("Helicobacter pylori" AND "gastric cancer") OR ("gut microbiome" AND "inflammatory bowel disease") OR ("oral microbiome" AND "systemic diseases"). Conclusions: The dysbiotic change in the oral cavity due to periodontitis is linked directly and indirectly to systemic diseases such as IBS, neurodegenerative diseases, muscle joint diseases, respiratory infections, and gastrointestinal cancer; this underscores the importance of maintaining oral hygiene for prophylaxis of oral diseases and the prevention of systemic diseases. A better understanding of the interconnections between oral health and systemic diseases will integrate oral health management to offer new prevention, diagnostic, and treatment opportunities to improve overall patient outcomes.

[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

The impact of VEGF on cancer metastasis and systemic disease.

Metastasis is the leading cause of cancer-associated mortality and the underlying mechanisms of cancer metastasis remain elusive. Both blood and lymphatic vasculatures are essential structures for mediating distal metastasis. The vasculature plays multiple functions, including accelerating tumor growth, sustaining the tumor microenvironment, supplying growth and invasive signals, promoting metastasis, and causing cancer-associated systemic disease. VEGF is one of the key angiogenic factors in tumors and participates in the initial stage of tumor development, progression and metastasis. Consequently, VEGF and its receptor-mediated signaling pathways have become one of the most important therapeutic targets for treating various cancers. Today, anti-VEGF-based antiangiogenic drugs (AADs) are widely used in the clinic for treating different types of cancer in human patients. Despite nearly 20-year clinical experience with AADs, the impact of these drugs on cancer metastasis and systemic disease remains largely unknown. In this review article, we focus our discussion on tumor VEGF in cancer metastasis and systemic disease and mechanisms underlying AADs in clinical benefits.

Metabolomic phenotyping of obesity for profiling cardiovascular and ocular diseases.

BACKGROUND: We aimed to evaluate the impacts of metabolomic body mass index (metBMI) phenotypes on the risks of cardiovascular and ocular diseases outcomes. METHODS: This study included cohorts in UK and Guangzhou, China. By leveraging the serum metabolome and BMI data from UK Biobank, this study developed and validated a metBMI prediction model using a ridge regression model among 89,830 participants based on 249 metabolites. Five obesity phenotypes were obtained by metBMI and actual BMI (actBMI): normal weight (NW, metBMI of 18.5-24.9 kg/m2), overweight (OW, metBMI of 25-29.9 kg/m2), obesity (OB, metBMI ≥ 30 kg/m2), overestimated (OE, metBMI-actBMI > 5 kg/m2), and underestimated (UE, metBMI-actBMI < - 5 kg/m2). Additional participants from the Guangzhou Diabetes Eye Study (GDES) were included for validating the hypothesis. Outcomes included all-cause and cardiovascular (CVD)-cause mortality, as well as incident CVD (coronary heart disease, heart failure, myocardial infarction [MI], and stroke) and age-related eye diseases (age-related macular degeneration [AMD], cataracts, glaucoma, and diabetic retinopathy [DR]). RESULTS: In the UKB, although OE group had lower actBMI than NW group, the OE group had a significantly higher risk of all-cause mortality than those in NW prediction group (HR, 1.68; 95% CI 1.16-2.43). Similarly, the OE group had a 1.7-3.6-fold higher risk than their NW counterparts for cardiovascular mortality, heart failure, myocardial infarction, and coronary heart disease (all P < 0.05). In addition, risk of age-related macular denegation (HR, 1.96; 95% CI 1.02-3.77) was significantly higher in OE group. In the contrast, UE and OB groups showed similar risks of mortality and of cardiovascular and age-related eye diseases (all P > 0.05), though the UE group had significantly higher actBMI than OB group. In the GDES cohort, we further confirmed the potential of metabolic BMI (metBMI) fingerprints for risk stratification of cardiovascular diseases using a different metabolomic approach. CONCLUSIONS: Gaps of metBMI and actBMI identified novel metabolic subtypes, which exhibit distinctive cardiovascular and ocular risk profiles. The groups carrying obesity-related metabolites were at higher risk of mortality and morbidity than those with normal health metabolites. Metabolomics allowed for leveraging the future of diagnosis and management of 'healthily obese' and 'unhealthily lean' individuals.

Feature tracking cardiac magnetic resonance imaging to assess cardiac manifestations of systemic diseases.

Feature-tracking cardiac magnetic resonance (FT-CMR), with the ability to quantify myocardial deformation, has a unique role in the evaluation of subclinical myocardial abnormalities. This review aimed to evaluate the clinical use of cardiac FT-CMR-based myocardial strain in patients with various systemic diseases with cardiac involvement, such as hypertension, diabetes, cancer-therapy-related toxicities, amyloidosis, systemic scleroderma, myopathies, rheumatoid arthritis, thalassemia major, and coronavirus disease 2019 (COVID-19). We concluded that FT-CMR-derived strain can improve the accuracy of risk stratification and predict cardiac outcomes in patients with systemic diseases prior to symptomatic cardiac dysfunction. Furthermore, FT-CMR is particularly useful for patients with diseases or conditions which are associated with subtle myocardial dysfunction that may not be accurately detected with traditional methods. Compared to patients with cardiovascular diseases, patients with systemic diseases are less likely to undergo regular cardiovascular imaging to detect cardiac defects, whereas cardiac involvement in these patients can lead to major adverse outcomes; hence, the importance of cardiac imaging modalities might be underestimated in this group of patients. In this review, we gathered currently available data on the newly introduced role of FT-CMR in the diagnosis and prognosis of various systemic conditions. Further research is needed to define reference values and establish the role of this sensitive imaging modality, as a robust marker in predicting outcomes across a wide spectrum of patients.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

Comparison of oxidative stress markers in the saliva, gingival crevicular fluid, and serum samples of pregnant women with gestational diabetes and healthy pregnant women.

BACKGROUND AND OBJECTIVE: To compare oxidative stress (OS) markers in the saliva, gingival crevicular fluid (GCF), and serum samples of pregnant women with gestational diabetes (GDM) and healthy pregnant women and to investigate the association between periodontal health/diseases and OS and GDM. METHOD: Eighty women with GDM and 80 healthy pregnant women were included in the study. Medical and clinical anamnesis was obtained from all the pregnant women included in the study, and their plaque index (PI), gingival index (GI), bleeding on probing (BoP), probing pocket depth (PPD), and clinical attachment level (CAL) measurements were performed. GCF, saliva, and serum samples were collected for the measurements of the local and systemic total antioxidant status (TAS) and total oxidant status (TOS). RESULTS: Clinical periodontal parameters were found to be significantly higher in the GDM group compared to the control group. The serum and saliva TAS, TOS, and TAS/TOS values were significantly lower in the GDM group than in the control group. In the analysis of the GCF samples, the mean TAS and TAS/TOS values were significantly lower and the TOS value was significantly higher in the GDM group than in the control group. The multivariate reduced model indicated that gravidity, salivary TAS/TOS, and GCF TAS were significant independent variables in the development of GDM (p < .05). CONCLUSION: Our results indicated that the OS of serum, saliva, and GCF samples increased in patients with GDM compared to healthy pregnant women. The role of local OS parameters in GDM may be associated with elevated clinical periodontal parameters.

Ocular images-based artificial intelligence on systemic diseases.

PURPOSE: To provide a summary of the research advances on ocular images-based artificial intelligence on systemic diseases. METHODS: Narrative literature review. RESULTS: Ocular images-based artificial intelligence has been used in a variety of systemic diseases, including endocrine, cardiovascular, neurological, renal, autoimmune, and hematological diseases, and many others. However, the studies are still at an early stage. The majority of studies have used AI only for diseases diagnosis, and the specific mechanisms linking systemic diseases to ocular images are still unclear. In addition, there are many limitations to the research, such as the number of images, the interpretability of artificial intelligence, rare diseases, and ethical and legal issues. CONCLUSION: While ocular images-based artificial intelligence is widely used, the relationship between the eye and the whole body should be more clearly elucidated.

Mönckeberg's medial arteriosclerosis in the oral and maxillofacial region: A pilot study.

OBJECTIVE: To evaluate the prevalence of medial vascular calcifications in the oral and maxillofacial region and their association with systemic diseases. MATERIALS AND METHODS: The study included 211 consecutive patients with systemic diseases (January 2015-May 2016). Medical history and radiographic images were evaluated. Univariate analysis (t-test) was performed for continuous variables (age). The Chi square test was applied for the categorical variables (Mönckeberg medial arteriosclerosis [MMA], gender). RESULTS: There was a 6.2% prevalence of MMA. The mean age of patients with MMA was 65.46 ± 13.38. The prevalence of kidney disease in patients with MMA was significantly higher than in those without MMA (p < 0.001). This finding was maintained even after adjusting for other systemic diseases (OR = 31.84 [8.63-136.78]). CONCLUSION: A significant prevalence of MMA in kidney disease patients was observed in this pilot study.

Severe chronic obstructive pulmonary disease is associated with reduced oral health conditions.

OBJECTIVES: This study aimed to investigate the association of explicitly severe chronic obstructive pulmonary disease (COPD) with oral conditions considering in-depth shared risk factors. METHODS: A case-control study was conducted with 104 participants, 52 with severe COPD and 52 matched controls without COPD. Dental and periodontal status were clinically assessed and oral health-related quality of life (OHRQoL) by OHIP-G14-questionnaire. RESULTS: Between COPD- and control-group, there were no statistically significant differences regarding age (66.02 ± 7.30), sex (female: 52 [50%]), smoking history (44.69 ± 23.23 pack years) and number of systemic diseases (2.60 ± 1.38). COPD patients demonstrated significantly fewer remaining teeth (12.58 ± 9.67 vs. 18.85 ± 6.24, p < 0.001) besides higher DMFT (decayed, missing and filled teeth) index (21.12 ± 5.83 vs. 19.10 ± 3.91, p = 0.036). They had significantly greater probing pocket depths (PPD: 3.24 mm ± 0.71 mm vs. 2.7 mm ± 0.37 mm, p < 0.001) and bleeding on probing (BOP: 34.52% ± 22.03% vs. 22.85% ± 17.94%, p = 0.003) compared to controls, but showed no significant difference in clinical attachment level or staging of periodontitis. The OHIP-G14 sum score was significantly higher in COPD patients (7.40 ± 7.28 vs. 3.63 ± 4.85, p = 0.002). Common risk factors such as educational status, physical activity, dentist visit frequency, oral hygiene regimens and dietary habits were less favourable in patients with COPD. CONCLUSIONS: COPD was significantly associated with higher tooth loss, PPD, BOP and DMFT besides lower OHRQoL.

A comparative retrospective study on the prevalence and therapeutic treatment of dental agenesis between healthy children and children with systemic disease or congenital malformation.

BACKGROUND: Dental agenesis (DA) in the permanent dentition is one of the most common dental anomalies, with a prevalence up to 2-10%. Therefore, the aim of this retrospective study was to investigate the prevalence and therapeutic treatment of DA in healthy children (HC) compared to children with systemic disease or congenital malformation (SD/CM). METHODS: Out of 3407 patients treated at the Department of Paediatric Dentistry of the Justus Liebig University Giessen (Germany) between January 2015 and December 2020, a total of 1067 patients (594 female, 473 male) aged between 4.5 and 18 years were included in this study due to DA. Besides the patients' general medical history and therapeutic treatments, panoramic radiographs were analysed. RESULTS: In contrast to the HC group with 9.7% DA, the SD/CM group showed a significantly higher prevalence of DA (19.8%; p < 0.05). The latter group was further classified into children with ectodermal dysplasia (4.4%), down syndrome (8.2%), cleft lip and palate (4.4%), intellectual disability/developmental delay (16.4%), and other genetic/organic diseases without intellectual disability (45.9%). Regarding therapeutic treatments, the HC group (59.5%) was significantly more often treated with an orthodontic gap opening compared to the SD/CM group (42.6%; p < 0.05), followed by orthodontic gap closing 36.5% in the HC group and 22.9% in the SD/CM group (p < 0.05), whereas no treatment was predominantly performed in the SD/CM group (37.7%) compared to the HC group (4%; p < 0.05). Furthermore, 50% in the SD/CM group required general anaesthesia for therapeutic treatment (vs. 8.1% in the HC group; p < 0.05). CONCLUSIONS: Children with SD/CM suffered more often from DA compared to HC that underlines multi- and interdisciplinary treatment of utmost importance. Furthermore, due to intellectual disability, common treatment methods can be complicated by insufficient compliance. This fact underlines the importance of an early attempt to establish the necessary cooperation enabling children with SD/CM to receive therapy.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E-deficient mice.

AIM: There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. METHODOLOGY: Twenty-four 5-week-old lipoprotein E knockout (apoE-/- ) mice were randomly divided into four groups: the CAP group, Con group, Co-CAP (cohoused with CAP) and Co-Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P. gingivalis was placed into the exposed pulp chamber, followed by coronal resin-based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co-CAP and Co-Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil-red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N-oxide (TMAO), and immunohistochemistry of flavin-containing monooxygenase 3 (FMO3) in liver were used to assess TMAO-related metabolic alterations. RESULTS: Alterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p < .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p < .05), which were positively correlated with serum TMAO levels (p < .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p < .05). CONCLUSION: Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.

Impact of systemic health on treatment outcomes in endodontics.

BACKGROUND: The healing of periapical lesions after root canal treatment (RCT) is not the result of the curative action of the treatment. The process of healing begins with inflammation, and is resolved by the clearance of the immunogen that induces the immune response. Then, the periapical tissue itself carries out the healing of the periapical lesion, by repair or by a combination of repair and regeneration, depending on the host's reparative response working properly. The ultimate objective of RCT is to achieve wound healing by removing the source of bacterial antigens and toxins, allowing chronic inflammatory tissue to become reparative tissue. Some systemic conditions increase the susceptibility of the host to infection or impair the tissue reparative response, maintaining the inflammatory process and periapical bone resorption after RCT. This can cause the failure of RCT and even the need for extraction of the affected tooth. OBJECTIVE: To analyse the scientific literature on the possible influence of systemic conditions on the treatment outcomes in endodontics, as well as to discuss the biological mechanisms that may be involved. METHODS: The search was carried out in PubMed, SCOPUS and EMBASE. The inclusion criteria established were original scientific articles reporting data about some systemic condition in relation to treatment outcomes in endodontics, including clinical studies and studies carried out in animal models. RESULTS: Systemic factors (age, nutrition, stress, hormones, smoking habits), and systemic diseases, such as diabetes, cardiovascular diseases, osteoporosis, HIV infection, inflammatory bowel disease, and others, can influence or interfere in the repair of periapical tissues after RCT. DISCUSSION: Some of these systemic diseases can alter bone turnover and fibroblast function, preventing or delaying periapical wound healing. Others can alter the microvasculature, reducing nutrients and oxygen supply to periapical tissues. As a result, these systemic conditions can decrease the success rate of RCT and provoke incomplete wound healing (typically granulomatous tissue formation) in the periapical region. CONCLUSIONS: The results of this narrative review show worse success rate of RCT, with higher percentage of postoperative radiolucent periapical lesions and higher proportion of non-retained teeth (RFT), associated with several systemic conditions, such as smoking habits and diabetes.

Is There An Association Between Periodontitis And Non-Alcoholic Fatty Liver Disease? A Systematic Review and Meta-Analysis.

BACKGROUND: Studies have reported varying relationships between periodontitis and non-alcoholic fatty liver disease (NAFLD). This review aimed to summarise evidence by pooling published data on the association between periodontitis and NAFLD. METHODS: PubMed, CENTRAL, Web of Science, and Embase databases were searched for cross-sectional, case-control, or cohort studies published up to 20th June 2022. The PICO statement was: In the general Population does the presence of periodontitis (Intervention) as compared to no periodontitis (Comparison) lead to NAFLD (Outcome). All included studies were to report the association between periodontitis and NAFLD using odds ratios (OR) or risk ratios with 95% confidence intervals (CI). Random effects meta-analysis was conducted to obtain pooled OR with 95% CI. RESULTS: Meta-analysis of seven studies with data of 192,815 participants found no association between periodontitis and NAFLD (OR: 1.04 95% CI: 0.97, 1.12). There was medium heterogeneity in the meta-analysis (I²=58%). The results did not change with the exclusion of any study. A small risk of NAFLD was noted in periodontitis patients on analysis of two cohort studies. Results were non-significant for other study types. Subgroup analysis based on the study population and diagnostic method for NAFLD also failed to find relationships. CONCLUSION: Current evidence fails to demonstrate a link between periodontitis and NAFLD.