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ABSTRACT: Background: Intellectual and developmental disabilities (IDDs), including autism spectrum disorder (ASD), often lead to sensory challenges and dental anxiety, complicating oral healthcare. Sensory adapted dental environment (SADE) can alleviate anxiety and enhance cooperation during dental procedures, but awareness and implementation among dentists remain limited. Objective: To assess general dentists' knowledge, attitudes, and practices regarding SADE and identify gaps for targeted educational programs. Methods: A survey of 500 dentists in Tamil Nadu, India, collected data on demographics, SADE knowledge, attitudes, and practices. Analysis included descriptive statistics and significance tests. Results: Most respondents were female (68.6%), aged 21–30 (90.9%), with a BDS degree (76.0%), and having 1–10 years of experience (94.8%). Primary fears for children in dental settings were injections (45.7%) and white coats (41.8%). Nonpharmacologic techniques were preferred by 86.8% of dentists. While 49.5% were aware of SADE, only 30.3% had implemented it. Most recognized its benefits (78.7%) and believed it reduces anxiety (81.9%). Despite interest (84.7%), concerns about costs (53.0%) hindered implementation. Conclusion: Strong interest and perceived benefits of SADE exist among dentists, but cost concerns and limited understanding hinder its implementation. Enhanced education and resources are vital for broader SADE adoption, potentially improving dental care for individuals with IDDs. [ABSTRACT FROM AUTHOR]

Objective: Differentiating forms of autoimmune encephalitis (AE) from other causes of seizures helps expedite immunotherapies in AE patients and informs studies regarding their contrasting pathophysiology. We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)‐based metabolomics could differentiate AE from drug‐resistant epilepsy (DRE), and stratify AE subtypes. Methods: This study recruited 238 patients: 162 with DRE and 76 AE, including 27 with contactin‐associated protein‐like 2 (CASPR2), 29 with leucine‐rich glioma inactivated 1 (LGI1) and 20 with N‐methyl‐d‐aspartate receptor (NMDAR) antibodies. Plasma samples across the groups were analyzed using NMR spectroscopy and compared with multivariate statistical techniques, such as orthogonal partial least squares discriminant analysis (OPLS‐DA). Results: The OPLS‐DA model successfully distinguished AE from DRE patients with a high predictive accuracy of 87.0 ± 3.1% (87.9 ± 3.4% sensitivity and 86.3 ± 3.6% specificity). Further, pairwise OPLS‐DA models were able to stratify the three AE subtypes. Plasma metabolomic signatures of AE included decreased high‐density lipoprotein (HDL, −(CH2)n−, –CH3), phosphatidylcholine and albumin (lysyl moiety). AE subtype‐specific metabolomic signatures were also observed, with increased lactate in CASPR2, increased lactate, glucose, and decreased unsaturated fatty acids (UFA, –CH2CH=) in LGI1, and increased glycoprotein A (GlycA) in NMDAR‐antibody patients. Interpretation: This study presents the first non‐antibody‐based biomarker for differentiating DRE, AE and AE subtypes. These metabolomics signatures underscore the potential relevance of lipid metabolism and glucose regulation in these neurological disorders, offering a promising adjunct to facilitate the diagnosis and therapeutics. [ABSTRACT FROM AUTHOR]

Activity of GFR/PI3K/AKT pathway inhibitors in glioblastoma clinical trials has not been robust. We hypothesized variations in the pathway between tumors contribute to poor response. We clustered GBM based on AKT pathway genes and discovered new subtypes then characterized their clinical and molecular features. There are at least 5 GBM AKT subtypes having distinct DNA copy number alterations, enrichment in oncogenes and tumor suppressor genes and patterns of expression for PI3K/AKT/mTOR signaling components. Gene Ontology terms indicate a different cell of origin or dominant phenotype for each subgroup. Evidence suggests one subtype is very sensitive to BCNU or CCNU (median survival 5.8 vs. 1.5 years; BCNU/CCNU vs other treatments; respectively). AKT subtyping advances previous approaches by revealing additional subgroups with unique clinical and molecular features. Evidence indicates it is a predictive marker for response to BCNU or CCNU and PI3K/AKT/mTOR pathway inhibitors. We anticipate Akt subtyping may help stratify patients for clinical trials and augment discovery of class-specific therapeutic targets.

Background: Local anesthetic systemic toxicity (LAST) in children occurs at an estimated rate of 8 per 100 000 blocks (95% CI 0.3 to 1.6). Due to the potential lethality of this iatrogenic complication, a better clarity of risk factors, clinical presentation, and prognosis may be clinically useful for contemporary treatment and prevention.Methods: An extensive literature search and detailed analysis of reported cases of LAST in patients less than 18 years of age published between April 2014 and August 2019 was performed. Clinical patterns were summarized.Results: Thirty-two cases of LAST were described in 17 published articles and 2 additional cases reported to lipidrescue.org, for a total of 34 cases. Three patients did not meet the inclusion criteria. Thirty-one cases were included in the analysis.Discussion: Infants represented a disproportionately large number of reports of LAST. The majority of local anesthetic doses were within currently published guidelines. Among the reported cases, penile and caudal blocks were the most commonly associated with LAST. Needle aspiration and test dosing with epinephrine failed to predict LAST with certainty. When LAST presented with severe cardiac compromise, intravenous lipid emulsion was given within 10 min in 43% of cases (13 of 30 reported cases). The vast majority of children were under general anesthesia when local anesthetic medications were administered. In children under general anesthesia, LAST presented with cardiac manifestations in 90% of cases (19 of 21 cases). There were no deaths or long-term morbidity reported. [ABSTRACT FROM AUTHOR]

Objective: To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this clinical setting.Methods: Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.Results: 10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. 9/23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (p<0.0001). Multivariate analysis identified six features which predicted autoantibody positivity (area under the curve=0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, MRI limbic system changes and the absence of conventional epilepsy risk factors. 11/14 (79%) patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score=0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (p<0.05).Conclusions: Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggests immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Vesicular nucleotide transporter (VNUT) is required for active accumulation of adenosine tri-phosphate (ATP) into vesicles for purinergic neurotransmission, however, the cell types that express VNUT in the central nervous system remain unknown. This study characterized VNUT expression within the mammalian retina and brain and assessed a possible functional role in purinergic signaling. Two native isoforms of VNUT were detected in mouse retina and brain based on RNA transcript and protein analysis. Using immunohistochemistry, VNUT was found to co-localize with tyrosine hydroxylase (TH) positive, dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, however, VNUT expression in extranigral non-DA neurons was also observed. In the retina, VNUT labeling was found to co-localize solely with TH-positive DA-cells. In the outer retina, VNUT-positive interplexiform cell processes were in close contact with horizontal cells and cone photoreceptor terminals, which are known to express P2 purinergic-receptors. In order to assess function, dissociated retinal neurons were loaded with fluorescent ATP markers (Quinacrine or Mant-ATP) and the DA marker FFN102, co-labeled with a VNUT antibody and imaged in real time. Fluorescent ATP markers and FFN102 puncta were found to co-localize in VNUT positive neurons and upon stimulation with high potassium, ATP marker fluorescence at the cell membrane was reduced. This response was blocked in the presence of cadmium. These data suggest DA neurons co-release ATP via calcium dependent exocytosis and in the retina this may modulate the visual response by activating purine receptors on closely associated neurons. [ABSTRACT FROM AUTHOR]

Introduction: Deep pits and fissures are more prone to caries development due to their complex morphological anatomy. Preventive measures, such as pit and fissure sealants, can help in the reduction of dental caries. Conventional sealants being hydrophobic in nature, require isolation. Sealants which are hydrophilic have been introduced as an alternative where isolation is difficult to achieve., Aim: To compare and evaluate the retention and marginal integrity of hydrophilic pit and fissure sealant (Embrace WetBond) with hydrophobic pit and fissure sealant (Clinpro) in permanent first molars., Materials and Methods: Sealants were applied randomly using the split-mouth design technique on 80 permanent first molars in children aged between 6 and 9 years and evaluation was done at 3, 6, 9, and 18 months., Results: The difference in retention rates between the groups was not significant using the Chi-squared test, though the WetBond group exhibited better results with 40% complete retention at the end of 18 months while in the Clinpro group, it was 37.50%. The marginal integrity in both the sealant groups was also found to be statistically insignificant. Caries incidence was found to be slightly higher in the Clinpro group., Conclusion: The clinical performance of Embrace WetBond was better when compared to Clinpro because of its moisture-tolerance capacity. Embrace Wetbond pit and fissure sealant can be the choice of material in cases where moisture control is a challenging issue., How to Cite This Article: Gyati O, Jain M, Sogi S, et al. Clinical Evaluation of Retention of Hydrophilic and Hydrophobic Pit and Fissure Sealants in Permanent First Molars: An 18 Months follow-up: Randomized Controlled Trial. Int J Clin Pediatr Dent 2023;16(2):350-356., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Thoracic high dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4-6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events., Competing Interests: Conflicts of Interest: None of the authors disclose conflicts of interest.