Link between gut microbiota dysbiosis and chronic kidney disease.

During chronic kidney disease (CKD), typical alterations in the gut microbiota are observed. The kidney no longer plays the role of the main excretory organ as this function is performed by the intestine. In CKD patients, an alteration of intestinal permeability and a degradation of the protective mucous layer are observed. These changes in the intestinal barrier allow the passage of bacterial material from the intestine to the bloodstream through the intestinal wall. This phenomenon contributes to the induction of the chronic inflammatory state, typical of CKD. In nephropathic patients, there is an increase in circulation of p-cresyl sulfate (p-CS), indoxyl sulphate (IS), indole-3 acetic acid (IAA) and trimethylamine-N-oxide (TMAO), all gut-derived uremic toxins. The changes in gut microbiota composition are related to CKD stage and this phenomenon is exacerbated in hemodialysis (HD) adult and pediatric patients. Interestingly, it is observed a positive shift in gut microbiota composition after renal transplantation and at the same time a reduction of circulating gut-derived uremic toxins. Either gut dysbiosis or uremic toxins accumulation contribute to the CKD onset and progression.

Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.

Developing and validating ultrasound-based radiomics models for predicting high-risk endometrial cancer.

OBJECTIVES: The primary aim of this study was to develop and validate radiomics models, applied to ultrasound images, capable of differentiating from other cancers high-risk endometrial cancer, as defined jointly by the European Society for Medical Oncology, European Society of Gynaecological Oncology and European Society for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) in 2016. The secondary aim was to develop and validate radiomics models for differentiating low-risk endometrial cancer from other endometrial cancers. METHODS: This was a multicenter, retrospective, observational study. From two participating centers, we identified consecutive patients with histologically confirmed diagnosis of endometrial cancer who had undergone preoperative ultrasound examination by an experienced examiner between 2016 and 2019. Patients recruited in Center 1 (Rome) were included as the training set and patients enrolled in Center 2 (Milan) formed the external validation set. Radiomics analysis (extraction of a high number of quantitative features from medical images) was applied to the ultrasound images. Clinical (including preoperative biopsy), ultrasound and radiomics features that were statistically significantly different in the high-risk group vs the other groups and in the low-risk group vs the other groups on univariate analysis in the training set were considered for multivariate analysis and for developing ultrasound-based machine-learning risk-prediction models. For discriminating between the high-risk group and the other groups, a random forest model from the radiomics features (radiomics model), a binary logistic regression model from clinical and ultrasound features (clinical-ultrasound model) and another binary logistic regression model from clinical, ultrasound and previously selected radiomics features (mixed model) were created. Similar models were created for discriminating between the low-risk group and the other groups. The models developed in the training set were tested in the validation set. The performance of the models in discriminating between the high-risk group and the other groups, and between the low-risk group and the other risk groups for both validation and training sets was compared. RESULTS: The training set comprised 396 patients and the validation set 102 patients. In the validation set, for predicting high-risk endometrial cancer, the radiomics model had an area under the receiver-operating-characteristics curve (AUC) of 0.80, sensitivity of 58.7% and specificity of 85.7% (using the optimal risk cut-off of 0.41); the clinical-ultrasound model had an AUC of 0.90, sensitivity of 80.4% and specificity of 83.9% (using the optimal cut-off of 0.32); and the mixed model had an AUC of 0.88, sensitivity of 67.3% and specificity of 91.0% (using the optimal cut-off of 0.42). For the prediction of low-risk endometrial cancer, the radiomics model had an AUC of 0.71, sensitivity of 65.0% and specificity of 64.5% (using the optimal cut-off of 0.38); the clinical-ultrasound model had an AUC of 0.85, sensitivity of 70.0% and specificity of 80.6% (using the optimal cut-off of 0.46); and the mixed model had an AUC of 0.85, sensitivity of 87.5% and specificity of 72.5% (using the optimal cut-off of 0.36). CONCLUSIONS: Radiomics seems to have some ability to discriminate between low-risk endometrial cancer and other endometrial cancers and better ability to discriminate between high-risk endometrial cancer and other endometrial cancers. However, the addition of radiomics features to the clinical-ultrasound models did not result in any notable increase in performance. Other efficacy studies and further effectiveness studies are needed to validate the performance of the models. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy of the Andresen activator before peak growth in class II patients.

Andresen activator (AA) is a functional appliance used to correct Class II malocclusion in growing patients. It corrects the malocclusion stimulating mandibular growth and determining a palatoversion of the upper incisors and a vestibularization of the lower incisors. The aim of this study was to analyze the treatment efficacy of class II malocclusion due to mandibular hypodevelopment before peak growth. Fourteen subjects with class II relationship of the skeletal bases and cervical vertebrae maturation stage 1 or 2 were enrolled in the study. Cephalometric analyses were carried out using landmarks derived from the analyses of Pancherz, Ricketts, Tweed and Steiner. A significant decrease (P less than 0.05) in ANB angle was found (-2.29±3.05°) after treatment, which was expression of an improvement in maxillo-mandibular sagittal skeletal relationships. There was also a significant reduction of OJ after treatment (-4.44±2.36 mm; P less than 0.001), indicating a vestibularization of the mandibular incisors and a palatoversion of the maxillary incisors, and a correction of the molar relationship. The favorable effects of the Andresen activator for the correction of the mandibular defect can be found even prior to peak growth; the achieved class I relationship maintains a correct mandible position in time, ensuring a proper skeletal growth. .

Evaluation of pain, swelling and trismus after extraction of impacted third molars relative to the use of betamethasone in submucusal infiltration.

The aim of this study was to evaluate the anti-inflammatory effect of a single 4 mg injection of submucosal betamethasone after extraction of impacted third molars. Single-centre, single-blinded, parallel group study; Forty-three patients were submitted to impacted third molar extraction. In this study, 4 mg single-dose submucosal betamethasone was injected in the interventional group, while in the control group nothing was injected. Postoperative measurement included pain via the VAS scale, swelling and trismus with facial measurements and maximum mouth openings, and finally nerve sensitivity. There was a significant difference between the two groups regarding trismic pain and edema. The use of a single 4 mg submucosal betamethasone injection leads to a reduction of oedema, trismus and pain in patients undergoing impacted third molar extraction. .

Tooth agenesis: part 2. Orthodontic treatment and prosthetic possibilities.

Dental agenesis has a great clinical significance due to its frequency during daily practice and the therapeutic problems that can arise from it. This paper will explore all the aspects to consider in order creating a proper multidisciplinary treatment plan: in particular, orthodontic, prosthetic and implantologic therapeutic alternatives are described for the rehabilitation of the different areas of the dental arches. In fact, dental agenesis is a problem that often requires the intervention of specialists from the different fields of dentistry and its treatment must meet aesthetics needs, stomatognathic function and patient satisfaction.

Bi-layered collagen nano-structured membrane prototype collagen matrix CM-10826 for oral soft tissue regeneration: an in vivo ultrastructural study on 13 patients.

A new developed collagen matrix CM-10826 (CM) of porcine origin designed to be used as oral soft tissue substitute was investigated before and after implantation by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). In a case series biopsy specimens were harvested from thirteen patients at 10, 20, 30, 43 days after abutment surgery for uncovering dental implants. The in vivo histological evaluations of each patient were performed via micro-coring of newly formed oral mucosa in the area covered by CM (test side) or left uncovered (control). Results showed that CM can be integrated in connective and epithelial tissues within 10 days, can be completely resorbed within 20 days and it is able to reduce inflammatory infiltrates and to stimulate both fibroblast/epithelial cell proliferation and neo-angiogenesis. Generally it seems to be superior in promoting soft tissue healing compared to that induced by secondary intention healing. Furthermore, it is able to act as a scaffold for soft-tissue regeneration, allowing the proliferation of keratinocytes from the wound edges and favoring neovascularization and growth of connective tissue in the mesh of porous layer. It appears that a CM might function in oral surgery as a substitute for autologous grafts and to avoid secondary intention healing in soft tissue defects.

An overview of socket preservation.

Socket preservation is a surgical procedure whose aim is to limit the physiological resorption of the alveolar ridge that occurs after a dental extraction, in order to have sufficient bone to perform an implant placement. 16 articles regarding socket preservation procedures were identified through scientific archives and analysed. The biological rationale, the graft materials and the predictive factors are identified to help the clinicians in their practice. Socket preservation is an effective treatment to prevent bone resorption if performed after an atraumatic extraction with the use of biomaterials and membranes. It is also important not to forget local and systemic predictive factors.

Tooth agenesis: part 1. Incidence and diagnosis in orthodontics.

Dental agenesis has a great clinical significance due to its frequency during daily practice and the therapeutic problems that can arise from it. This paper will explore the incidence of dental agenesis, its diagnosis and how this anomaly affects the teeth differently. The second subsequent paper will look at its treatment and management.

Trans-nasal endoscopic and intra-oral combined approach for odontogenic cysts.

Maxillary cysts are a common finding in maxillofacial surgery, dentistry and otolaryngology. Treatment is surgical; a traditional approach includes Caldwell-Luc and other intra-oral approaches. In this article, we analyse the outcomes of 9 patients operated on using a combined intra-oral and trans-nasal approach to the aforementioned disease. Although the number of patients is small, the good results of this study suggest that the combined approach might be a reliable treatment option.

Predicting seizures in untreated temporal lobe epilepsy using point-process nonlinear models of heartbeat dynamics.

Symptoms of temporal lobe epilepsy (TLE) are frequently associated with autonomic dysregulation, whose underlying biological processes are thought to strongly contribute to sudden unexpected death in epilepsy (SUDEP). While abnormal cardiovascular patterns commonly occur during ictal events, putative patterns of autonomic cardiac effects during pre-ictal (PRE) periods (i.e. periods preceding seizures) are still unknown. In this study, we investigated TLE-related heart rate variability (HRV) through instantaneous, nonlinear estimates of cardiovascular oscillations during inter-ictal (INT) and PRE periods. ECG recordings from 12 patients with TLE were processed to extract standard HRV indices, as well as indices of instantaneous HRV complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra) obtained through definition of inhomogeneous point-process nonlinear models, employing Volterra-Laguerre expansions of linear, quadratic, and cubic kernels. Experimental results demonstrate that the best INT vs. PRE classification performance (balanced accuracy: 73.91%) was achieved only when retaining the time-varying, nonlinear, and non-stationary structure of heartbeat dynamical features. The proposed approach opens novel important avenues in predicting ictal events using information gathered from cardiovascular signals exclusively.

Restless legs syndrome and post polio syndrome: a case-control study.

BACKGROUND AND PURPOSE: The aim was to investigate the prevalence of restless legs syndrome (RLS), fatigue and daytime sleepiness in a large cohort of patients affected by post polio syndrome (PPS) and their impact on patient health-related quality of life (HRQoL) compared with healthy subjects. METHODS: PPS patients were evaluated by means of the Stanford Sleepiness Scale and the Fatigue Severity Scale (FSS). The Short Form Health Survey (SF-36) questionnaire was utilized to assess HRQoL in PPS. RLS was diagnosed when standard criteria were met. Age and sex matched healthy controls were recruited amongst spouses or friends of PPS subjects. RESULTS: A total of 66 PPS patients and 80 healthy controls were enrolled in the study. A significantly higher prevalence of RLS (P < 0.0005; odds ratio 21.5; 95% confidence interval 8.17-57) was found in PPS patients (PPS/RLS+ 63.6%) than in healthy controls (7.5%). The FSS score was higher in PPS/RLS+ than in PPS/RLS- patients (P = 0.03). A significant decrease of SF-36 scores, including the physical function (P = 0.001), physical role (P = 0.0001) and bodily pain (P = 0.03) domains, was found in PPS/RLS+ versus PPS/RLS- patients. Finally, it was found that PPS/RLS+ showed a significant correlation between International Restless Legs Scale score and FSS (P < 0.0001), as well as between International Restless Legs Scale score and most of the SF-36 items (physical role P = 0.0018, general health P = 0.0009, vitality P = 0.0022, social functioning P = 0.002, role emotional P = 0.0019, and mental health P = 0.0003). CONCLUSION: Our findings demonstrate a high prevalence of RLS in PPS, and that RLS occurrence may significantly influence the HRQoL and fatigue of PPS patients. A hypothetical link between neuroanatomical and inflammatory mechanisms in RLS and PPS is suggested.

Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia.

Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD.

Salivary levels of IgA in healthy subjects undergoing active orthodontic treatment.

It has been reported that the immune system undergoes changes due to various factors, inflammation, surgery, medication, age and gender. The aim of this study was to investigate therapy-dependent changes of salivary IgA among healthy subjects undergoing active orthodontic treatment. The levels of IgA were determined at the beginning, and after 1,4, 8,16 weeks and 32 weaks of active orthodontic treatment. A total of 100 healthy individuals (aged 15-42 years) were enrolled in the study. Two milliliters of saliva were collected from all participants, and salivary IgA levels were measured by the ELISA technique. Mean salivary IgA levels were significantly higher in subjects after 1 week as compared to subjects at the beginning of orthodontic treatment (P < 0.01).. The mean levels of salivary IgA were significantly higher after 4 and 8 weeks of therapy than those observed in the control group (P < 0.00001 and P < 0.05, respectively) and reached the highest level at 16 weeks and then remained stable during treatment. Gender had no effect on the salivary levels of IgA as any significant differences were observed between men and women. The results highlight the importance of the salivary defense mechanism, translated through the increase in the levels of IgA, once orthodontic treatment is started.

Salivary calcium levels during orthodontic treatment.

Saliva contains many defense factors and plays a key role in oral metabolism. Salivary calcium, due to its affinity to be readily taken up by plaque, is an important factor not only with regard to the onset of periodontitis but also significantly with regard to dental health. The aim of this study was to estimate the salivary concentration of calcium, in a group of adults undergoing active orthodontic treatment. The levels of salivary calcium were determined at the beginning, and after 16 weeks of active orthodontic treatment. A total of 40 healthy individuals with a mean age of 23.9 years were enrolled in the study group, while 40 subjects served as controls. Two milliliters of saliva were collected from all participants, and salivary calcium levels were measured by biochemical assay. Mean salivary calcium levels were significantly higher in subjects after 16 weeks as compared to subjects at the beginning of orthodontic treatment and to the control group (p= 0.001). A significant association between higher salivary calcium levels and orthodontic treatment has been established, therefore, monitoring salivary calcium levels might be a useful tool to establish periodontal health status during active orthodontic treatment along with other inflammatory parameters.

Blood levels of interleukins in patients with ameloblastoma.

The aim of study was to determine and compare serum concentrations of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral ameloblastoma and healthy controls. Sixteen patients with ameloblastoma and 16 healthy controls were enrolled in this study. Cytokine concentrations were measured by chemiluminescent enzyme linked immunoassay. Serum concentrations of IL-1ß were below level of detection in all but four participants. No significant differences between the groups were observed in serum concentrations of IL-6. Serum TNF-α was significantly higher in control subjects than in ameloblastoma patients. Patients diagnosed with ameloblastoma have relatively normal levels of inflammatory cytokines in their blood and thus cannot be used as indicators of disease severity or for monitoring the treatment outcomes.

The benefits of Quercitin for dentistry and maxillofacial surgery: a systematic review.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is the major bioflavonoid in the human diet and belongs to an extensive class of polyphenolic flavonoid compounds almost ubiquitous in plants and plant food sources. The estimated average daily dietary intake of quercetin by an individual in the United States is 25 mg. In recent years, research about quercetin has evolved from animal studies to in vitro and in vivo studies and to human clinical studies and trials in order to establish its real properties and effects. In oral medicine, quercetin has been extensively studied, as a real increase in major diseases like cancers, periodontal disease, oral lesions, tooth decay and infections have been reported worldwide by health providers.It has been thus established that quercetin exhibits beneficial effects on oral health with its broad pharmacological properties, as preventive and therapeutic agent in dental caries with anti-inflammatory effect against oral pathogens, as well as an antioxidant and anti-cancer agent .The aim of the review is to present evidence-based aspect of treatment with quercetin in order to validate its tremendous role in dentistry and maxillofacial surgery.

Inclusion of all permanent mandibular molars and all maxillary second and third molars: a case report and review of the literature.

Simultaneous impactions of first, second, and third permanent molars on both mandibular sides together with the all maxillary second and third molars is a clinical situation never reported before in the literature and it might be a difficult challenge for maxillofacial surgeons and dentists. Early diagnosis and treatment of eruption disturbances contributes to optimal outcomes. This article reports the treatment of an adult with severe impaction of all mandibular first, second, and third molars together with all maxillary second and third molars, which limits the masticatory function and dental arch integrity. The impacted molars were surgically removed as the patients declined orthodontic treatment. The combined surgical-orthodontic approach represents a challenging treatment and the optimal one as it eliminates the need for prosthetic rehabilitation and implant replacement of the impacted molars, when accepted.