Knowledge and perception regarding molar incisor hypomineralisation among dental students and dental hygienist students in Spain: a cross-sectional study.

BACKGROUND: Molar incisor hypomineralisation (MIH) has a high prevalence in the Spanish pediatric population and is a precursor of carious lesions in teeth in which it is present. Although this pathology is included in the curricula of the Degree in Dentistry and the Training Cycle in Oral Hygiene in our country, the contents currently taught seem to be insufficient in relation to the level of knowledge that we have today about this condition. METHODS: A digital questionnaire of 18 questions was sent to a sample of 448 students attending the 4th and 5th year of the Degree in Dentistry and 2nd year of the Training Cycle in Oral Hygiene from different universities and vocational training centers in the Valencian Community. Descriptive and multivariate statistical analysis of the data was subsequently performed. RESULTS: Of the 290 questionnaires that were obtained, 53.8% were from students attending the 2nd year of a training course in oral hygiene and 46.2% were from students pursuing a degree in dentistry. Most of the respondents had heard about MIH (75.2%), mainly through master classes. However, most students had difficulties distinguishing MIH lesions from other lesions (58.3%). The degree of knowledge about MIH was greater among dental students in all the aspects evaluated: prevalence, diagnosis, prevention, and treatment. Of all the students, 83.8% were interested in increasing their training on MIH, especially in the areas of diagnosis and treatment. CONCLUSION: The results of the present study justify the need to expand the content on MIH, both theoretical and practical, in the educational curricula of the Degree in Dentistry and Integrated Vocational Training Centers in Spain.

Perioperative Opioid Consumption is Not Reduced in Cyanotic Patients Presenting for the Fontan Procedure.

Adequate pain control is a critical component of the perioperative approach to children undergoing repair of congenital heart disease (CHD). The impact of specific anatomic and physiologic disturbances on the management of analgesia has been largely unexplored at the present time. Studies in other pediatric populations have found an association between chronic hypoxemia and an increased sensitivity to the effects of opioid medications. The purpose of this retrospective study was to examine perioperative opioid administration and opioid-associated adverse effects in children undergoing surgical repair of CHD, with a comparison between patients with and without chronic preoperative cyanosis. Patients between the ages of 2 and 5 years whose tracheas were extubated in the operating room were included and were classified in the cyanotic group if they presented for the Fontan completion. The primary outcomes of interest were intraoperative and postoperative opioid administration. Secondary outcomes included pain scores and opioid-related side effects. The study cohort included 156 patients. Seventy-one underwent the Fontan procedure, twelve of which were fenestrated. Fontan patients received fewer opioids intraoperatively (11.33 µg/kg fentanyl equivalents versus 12.56 µg/kg, p = 0.03). However, there were no differences with regards to opioid consumption postoperatively and no correlation between preoperative oxygen saturation and total opioid administration. There were no differences between groups with regards to the respiratory rate nadir, postoperative pain scores, or the incidence of opioid-related side effects. In contrast to other populations with chronic hypoxemia exposure, children with cyanotic CHD did not appear to have increased sensitivity to the effects of opioid medications.

Altered frequencies of Th17 and Treg cells in children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder with an etiopathophysiology that seems to include immune alterations. Previous studies have suggested that variations in the levels of circulating T cell subpopulations may be involved in psychiatric diseases. However, the role of these cells in OCD remains unexplored. Hence, the present study aimed to examine the levels of T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells in patients with early-onset OCD and healthy controls. METHODS: The assessment was performed in 99 children and adolescents with OCD and 46 control subjects. The percentages of circulating Th1, Th2, Th17 and Treg cells were evaluated using flow cytometry. RESULTS: OCD patients had significantly higher levels of Th17 cells and lower percentages of Treg cells than healthy controls (p = 0.001 and p = 0.005, respectively). Furthermore, levels of Th17 cells progressively increased with the duration (p = 0.005) and severity of OCD (p = 0.008), whereas the percentages of Treg cells significantly declined with the duration of the disorder (p = 1.8 × 10-5). CONCLUSIONS: These results provide more evidence of the involvement of immune dysregulation, specifically an imbalance in the levels of circulating T helper and regulatory T cells, in the pathophysiology of early-onset OCD.

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder.

BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16-), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls. Moreover, proinflammatory cytokine production (GM-CSF, IL-1ß, IL-6, IL-8, and TNF-α) was measured by multiplex Luminex analysis in isolated monocyte cultures, in basal conditions, after exposure to lipopolysaccharide (LPS) to stimulate immune response or after exposure to LPS and the immunosuppressant dexamethasone. RESULTS: OCD patients had significantly higher percentages of total monocytes and CD16+ monocytes than healthy controls, mainly due to an increase in the intermediate subset but also in the non-classical monocytes. Monocytes from OCD patients released higher amounts of GM-CSF, IL-1ß, IL-6, IL-8, and TNF-α than healthy controls after exposure to LPS. However, there were no significant differences in basal cytokine production or the sensitivity of monocytes to dexamethasone treatment between both groups. Based on monocyte subset distribution and cytokine production after LPS stimulation, patients receiving psychoactive medications seem to have an intermediate inflammatory profile, that is, lower than non-medicated OCD individuals and higher than healthy controls. CONCLUSIONS: These results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD.

Visual diagnosis: 8-day-old hypotonic newborn with sparse hair.

A hypotonic newborn or infant with pale skin and sparse, friable, hypopigmented, or depigmented hair should have his copper and ceruloplasmin plasma levels evaluated because this is the usual clinical presentation of Menkes disease. Menkes disease is an X-linked recessive disease caused by a defect in the ATP7A gene, identified in 95% to 98% of the cases. Identifying the mutation confirms the diagnosis and allows for prenatal counseling and diagnosis in a future pregnancy. When administered within the first few months of life, copper histidinate, given subcutaneously in a dose of 50 to 150 mg/kg per day, appears to be effective not only by increasing life expectancy from 3 to 13 years but also by improving neurologic symptoms and neurodevelopmental outcomes in approximately 30% of the patients.

Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis.

Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth advantage was abolished in the gut of germ-free mice and restored in gnotobiotic mice colonized with members of the classes Bacteroidia and Clostridia. Reactive oxygen species (ROS) produced during the host response caused lysis of commensal microbes, resulting in the release of microbiota-derived aspartate that was used by S. Tm, in concert with nitrate-dependent anaerobic respiration, to outcompete commensal Enterobacteriaceae. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent S. Tm expansion during colitis.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients, such as iron. Pathogens scavenge iron using siderophores, including enterobactin; however, this strategy is counteracted by host protein lipocalin-2, which sequesters iron-laden enterobactin. Although this iron competition occurs in the presence of gut bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron and sustains its resilience in the inflamed gut by utilizing siderophores produced by other bacteria, including Salmonella, via a secreted siderophore-binding lipoprotein XusB. Notably, XusB-bound enterobactin is less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella, allowing the pathogen to evade nutritional immunity. Because the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the host-pathogen interactions and nutritional immunity.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients such as iron. Pathogens scavenge iron using siderophores, which is counteracted by the host using lipocalin-2, a protein that sequesters iron-laden siderophores, including enterobactin. Although the host and pathogens compete for iron in the presence of gut commensal bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron in the inflamed gut by utilizing siderophores produced by other bacteria including Salmonella, via a secreted siderophore-binding lipoprotein termed XusB. Notably, XusB-bound siderophores are less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella , allowing the pathogen to evade nutritional immunity. As the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the interactions between pathogen and host nutritional immunity.

Sphingolipid paracrine signaling impairs keratinocyte adhesion to promote melanoma invasion.

Melanoma is the deadliest form of skin cancer due to its propensity to metastasize. It arises from melanocytes, which are attached to keratinocytes within the basal epidermis. Here, we hypothesize that, in addition to melanocyte-intrinsic modifications, dysregulation of keratinocyte functions could initiate early-stage melanoma cell invasion. We identified the lysolipid sphingosine 1-phosphate (S1P) as a tumor paracrine signal from melanoma cells that modifies the keratinocyte transcriptome and reduces their adhesive properties, leading to tumor invasion. Mechanistically, tumor cell-derived S1P reduced E-cadherin expression in keratinocytes via S1P receptor dependent Snail and Slug activation. All of these effects were blocked by S1P2/3 antagonists. Importantly, we showed that epidermal E-cadherin expression was inversely correlated with the expression of the S1P-producing enzyme in neighboring tumors and the Breslow thickness in patients with early-stage melanoma. These findings support the notion that E-cadherin loss in the epidermis initiates the metastatic cascade in melanoma.

An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism.

The mechanisms by which the early-life microbiota protects against environmental factors that promote childhood obesity remain largely unknown. Using a mouse model in which young mice are simultaneously exposed to antibiotics and a high-fat (HF) diet, we show that Lactobacillus species, predominant members of the small intestine (SI) microbiota, regulate intestinal epithelial cells (IECs) to limit diet-induced obesity during early life. A Lactobacillus-derived metabolite, phenyllactic acid (PLA), protects against metabolic dysfunction caused by early-life exposure to antibiotics and a HF diet by increasing the abundance of peroxisome proliferator-activated receptor γ (PPAR-γ) in SI IECs. Therefore, PLA is a microbiota-derived metabolite that activates protective pathways in the small intestinal epithelium to regulate intestinal lipid metabolism and prevent antibiotic-associated obesity during early life.

Evaluation of AQP4 functional variants and its association with fragile X-associated tremor/ataxia syndrome.

Introduction: Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult FMR1 premutation carriers (55-200 CGGs). Clinical symptoms in FXTAS patients usually begin with an action tremor. After that, different findings including ataxia, and more variably, loss of sensation in the distal lower extremities and autonomic dysfunction, may occur, and gradually progress. Cognitive deficits are also observed, and include memory problems and executive function deficits, with a gradual progression to dementia in some individuals. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the central nervous system. Changes in AQP4 activity and expression have been implicated in several central nervous system disorders. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with brain-water homeostasis, and neurodegeneration disease. To date, this association has not been studied in FXTAS. Methods: To investigate the association of AQP4 SNPs with the risk of presenting FXTAS, a total of seven common AQP4 SNPs were selected and genotyped in 95 FMR1 premutation carriers with FXTAS and in 65 FMR1 premutation carriers without FXTAS. Results: The frequency of AQP4-haplotype was compared between groups, denoting 26 heterozygous individuals and 5 homozygotes as carriers of the minor allele in the FXTAS group and 25 heterozygous and 2 homozygotes in the no-FXTAS group. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of FXTAS. Discussion: Although AQP4 has been implicated in a wide range of brain disorders, its involvement in FXTAS remains unclear. The identification of novel genetic markers predisposing to FXTAS or modulating disease progression is critical for future research involving predictors and treatments.

Salmonella enterica serovar Typhimurium uses anaerobic respiration to overcome propionate-mediated colonization resistance.

The gut microbiota benefits the host by limiting enteric pathogen expansion (colonization resistance), partially via the production of inhibitory metabolites. Propionate, a short-chain fatty acid produced by microbiota members, is proposed to mediate colonization resistance against Salmonella enterica serovar Typhimurium (S. Tm). Here, we show that S. Tm overcomes the inhibitory effects of propionate by using it as a carbon source for anaerobic respiration. We determine that propionate metabolism provides an inflammation-dependent colonization advantage to S. Tm during infection. Such benefit is abolished in the intestinal lumen of Salmonella-infected germ-free mice. Interestingly, S. Tm propionate-mediated intestinal expansion is restored when germ-free mice are monocolonized with Bacteroides thetaiotaomicron (B. theta), a prominent propionate producer in the gut, but not when mice are monocolonized with a propionate-production-deficient B. theta strain. Taken together, our results reveal a strategy used by S. Tm to mitigate colonization resistance by metabolizing microbiota-derived propionate.

Diagnostic Validity in Occlusal Caries Detection of ICDAS II, DIAGNOdent, Radiography and a Combination of the Three Methods: An In Vitro Study.

In this study, we compare the efficacy and diagnostic concordance of the ICDAS, the radiographic criterion and the instrument known as the DIAGNOdent fluorescence laser pen on occlusal caries lesions using a histological section as the gold standard. Of 100 teeth that did not present cavitated occlusal lesions or occlusal fillings, 80 were chosen through a randomization program and examined by two previously trained and calibrated researchers. Subsequently, the teeth were sectioned with a diamond disk and observed under an optical microscope. The results were studied for caries with a limit established in enamel and caries with extension to dentin. The intra-examiner (0.821-0.933) and inter-examiner (0.817-0.924) reproducibility obtained for both ICDAS and DIAGNOdent for the diagnosis of borderline enamel caries was high. Similarly, intra-examiner (0.686-1.000) and inter-examiner (0.809-0.944) reproducibility for diagnosis of caries with dentin extension was also high for both methods. The sensitivity obtained was 0.76 (ICDAS), 0.87 (DIAGNOdent) and 0.58 (Rx), whereas the specificity obtained was 0.66 (ICDAS), 0.4 (DIAGNOdent) and 0.77 (Rx) for lesions limited to enamel. For lesions with extension to dentin, the sensitivity obtained was 0.73 (ICDAS), 0.82 (DIAGNOdent) and 0.09 (Rx), and the specificity obtained was 0.79 (ICDAS), 0.52 (DIAGNOdent) and 0.97 (Rx). Sensitivity increases in both cases by combining diagnostic methods. In conclusion, ICDAS and DIAGNOdent are better diagnostic methods than Rx for the detection of occlusal caries, and the combination of these methods helps to obtain a better diagnosis.

Unplanned Postoperative Reintubation in Children with Bronchial Asthma.

Unplanned postoperative reintubation is a serious complication that may increase postsurgical hospital length of stay and mortality. Although asthma is a risk factor for perioperative adverse respiratory events, its association with unplanned postoperative reintubation in children has not been comprehensively examined. Our aim was to determine the association between a preoperative comorbid asthma diagnosis and the incidence of unplanned postoperative reintubation in children. This was a retrospective cohort study comprising of 194,470 children who underwent inpatient surgery at institutions participating in the National Surgical Quality Improvement Program-Pediatric. The primary outcome was the association of preoperative asthma diagnosis with early, unplanned postoperative reintubation (within the first 72 hours following surgery). We also evaluated the association between bronchial asthma and prolonged hospital length of stay (longer than the 75th percentile for the cohort). The incidence of unplanned postoperative reintubation in the study cohort was 0.5% in patients with a history of asthma compared with 0.2% in patients without the diagnosis (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.71-2.89). This association remained significant after controlling for several clinical characteristics (OR: 1.54, 95% CI: 1.17-2.20). Additionally, asthmatic children were more likely to require a hospital length of stay longer than the 75th percentile for the study cohort (adjusted OR: 1.05, 95% CI: 1.01-1.10). Children with preoperative comorbid asthma diagnosis have an increased incidence of early, unplanned postoperative reintubation and prolonged postoperative hospitalization following inpatient surgery. By identifying these patients as having higher perioperative risks, it may be possible to institute strategies to improve their outcomes.

Intestinal Inflammation Promotes MDL-1+ Osteoclast Precursor Expansion to Trigger Osteoclastogenesis and Bone Loss.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation, but many patients experience extra-intestinal disease. Bone loss is one common extra-intestinal manifestation of IBD that occurs through dysregulated interactions between osteoclasts and osteoblasts. Systemic inflammation has been postulated to contribute to bone loss, but the specific pathologic mechanisms have not yet been fully elucidated. We hypothesized that intestinal inflammation leads to bone loss through increased abundance and altered function of osteoclast progenitors. METHODS: We used chemical, T cell driven, and infectious models of intestinal inflammation to determine the impact of intestinal inflammation on bone volume, the skeletal cytokine environment, and the cellular changes to pre-osteoclast populations within bone marrow. Additionally, we evaluated the potential for monoclonal antibody treatment against an inflammation-induced osteoclast co-receptor, myeloid DNAX activation protein 12-associating lectin-1 (MDL-1) to reduce bone loss during colitis. RESULTS: We observed significant bone loss across all models of intestinal inflammation. Bone loss was associated with an increase in pro-osteoclastogenic cytokines within the bone and an expansion of a specific Cd11b-/loLy6Chi osteoclast precursor (OCP) population. Intestinal inflammation led to altered OCP expression of surface receptors involved in osteoclast differentiation and function, including the pro-osteoclastogenic co-receptor MDL-1. OCPs isolated from mice with intestinal inflammation demonstrated enhanced osteoclast differentiation ex vivo compared to controls, which was abrogated by anti-MDL-1 antibody treatment. Importantly, in vivo anti-MDL-1 antibody treatment ameliorated bone loss during intestinal inflammation. CONCLUSIONS: Collectively, these data implicate the pathologic expansion and altered function of OCPs expressing MDL-1 in bone loss during IBD.

Relationship between Periodontal Condition of the Pregnant Woman with Preterm Birth and Low Birth Weight.

The aim of this study was to determine the association between the mother's periodontal condition and perinatal complications, such as preterm birth (PTB) and/or low birth weight (LBW), in a cohort of women in Valencia, Spain. Other related factors, such as tobacco, were also analysed. A prospective cohort study was carried out in a sample of 102 women with a single foetus and ages ranging between 18 and 42 years. Sociodemographic and obstetric variables, caries status, percentage of bleeding, clinical attachment loss (CAL), and probing pocket depth (PPD) data have been collected and analysed. The mean age was 32.4 years, and the BMI was normal. The average weight of new-borns (NB) was 3034 g. A total of 9.8% of the women smoked during their pregnancy. Bleeding percentage was 16.43% (SD 14.81%) and PPDs > 3 mm 8.8 (SD 11.08). The mean of CAL > 0 mm was 1.14 (SD 2.83). The frequency of PTB and LBW was 26%. No statistically significant differences were found between probing depth > 3 mm or CAL > 1 mm, with PTB and/or LBW. Periodontal disease in the mother was not statistically significantly related to either PTB or LBW. Tobacco use during pregnancy showed a statistical significance linked to LBW, but not with PTB.

Anesthesia for thoracic surgery in infants and children.

The management of infants and children presenting for thoracic surgery poses a variety of challenges for anesthesiologists. A thorough understanding of the implications of developmental changes in cardiopulmonary anatomy and physiology, associated comorbid conditions, and the proposed surgical intervention is essential in order to provide safe and effective clinical care. This narrative review discusses the perioperative anesthetic management of pediatric patients undergoing noncardiac thoracic surgery, beginning with the preoperative assessment. The considerations for the implementation and management of one-lung ventilation (OLV) will be reviewed, and as will the anesthetic implications of different surgical procedures including bronchoscopy, mediastinoscopy, thoracotomy, and thoracoscopy. We will also discuss pediatric-specific disease processes presenting in neonates, infants, and children, with an emphasis on those with unique impact on anesthetic management.

Need for Orthodontic Treatment in Pupils Aged between 12 and 15 in the Valencian Region (Spain).

The World Health Organization recommends carrying out periodic epidemiological studies in order to provide a basis for the evaluation of the state of health of the population at any given time; in doing so, action strategies can be established for the treatment of different pathologies. The objective of this study is to evaluate the need for orthodontic treatment in adolescents at school aged between 12 and 15 in the Spanish autonomous region known as Comunidad Valenciana (hereafter: Valencian Region). A cross-sectional study was carried out on a sample of 539 12-year-old schoolchildren and 460 15-year-olds, respectively, selected by cluster sampling and representative of the school-aged population of the Valencian Region, using the IOTN-DHC, IOTN-AC, and DAI indices. The need for specific orthodontic treatment according to the IOTN-DHC was 12.6% at 12 years and 7% at 15. For the IOTN-AC and DAI indices, the treatment needs were 4.3% and 0.9% at 12 years and 30.1% and 20.9% at the age of 15. These results were similar to those obtained in the previous study carried out on the same target population. There was no significant association between the need for treatment and gender or social class. We conclude that the need for orthodontic treatment presents values similar to those obtained in 2010.

High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide.

A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.