Mating-induced release of oxytocin in the mouse lateral septum: Implications for social fear extinction.

In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and females, both of which have been linked to reduced stress responsiveness and anxiolysis. Also, in a murine model of social fear conditioning (SFC), enhanced brain OXT signaling in lactating mice, specifically in the lateral septum (LS), was reported to underlie reduced social fear expression. Here, we studied the effects of mating in male mice on anxiety-related behaviour, social (and cued) fear expression and its extinction, and the activity of OXT neurons reflected by cFos expression and OXT release in the LS and amygdala. We further focused on the involvement of brain OXT in the mating-induced facilitation of social fear extinction. We could confirm the anxiolytic effect of mating in male mice irrespective of the occurrence of ejaculation. Further, we found that only successful mating resulting in ejaculation (Ej+) facilitated social fear extinction, whereas mating without ejaculation (Ej-) did not. In contrast, mating did not affect cues fear expression. Using the cellular activity markers cFos and pErk, we further identified the ventral LS (vLS) as a potential region participating in the effect of ejaculation on social fear extinction. In support, microdialysis experiments revealed a rise in OXT release within the LS, but not the amygdala, during mating. Finally, infusion of an OXT receptor antagonist into the LS before mating or into the lateral ventricle (icv) after mating demonstrated a significant role of brain OXT receptor-mediated signaling in the mating-induced facilitation of social fear extinction.

Risk factors for Peri-implantitis: An umbrella review of meta-analyses of observational studies and assessment of biases.

OBJECTIVES: To perform a comprehensive quantitative and qualitative analysis of the findings from previously published meta-analyses and to assess existing biases. DATA/SOURCES: A search was conducted for meta-analyses of observational studies investigating the association between any risk factor and peri­implantitis in PubMed, Scopus, Cochrane Database of Systematic Reviews, and Epistemonikos, from inception until October 2023 (PROSPERO: CRD42024512408). STUDY SELECTION: From a total of 5002 publications, 51 full-text articles were evaluated for eligibility, and 12 articles that described 41 unique meta-analyses evaluating the association between risk factors and periimplantitis were selected. Among 41 associations, 24 associations were significant. None of the associations were graded as convincing evidence. Two associations, presence of periodontitis (OR = 3.84 [95 % CI 2.58,5.72]) and cigarette smoking (RR=2.07 [95 % CI 1.41,3.04]) were graded as highly suggestive. Eight associations, diabetes mellitus, hyperglycaemia, lack of prophylaxis, history of chronic periodontal disease, ongoing or history of periodontal disease, implants located in the anterior region of the jaw (maxillary and mandibular), osteoprotegerin (OPG) gene polymorphisms, and lack of keratinized mucosal width were graded as suggestive evidence. CONCLUSIONS: Periodontitis and cigarette smoking are highly suggestive risk factors for peri­implantitis. The remaining risk factors which are suggestive require more high-quality studies to be performed to upgrade the level of evidence. CLINICAL SIGNIFICANCE: The highly suggestive and suggestive risk factors for peri­implantitis summarized in this umbrella review should be rigorously assessed, monitored and managed by clinicians to reduce the risk peri­implantitis, as well as to form part of the preoperative consent process.

Comparative effectiveness of interventions for the treatment of peri-implantitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Extensive research has been carried out on the various aspects of diagnosing and treating peri-implantitis. However, clinical guidelines for the management of peri-implantitis based on high quality evidence are lacking. PURPOSE: The purpose of this systematic review with network meta-analysis was to analyze the current evidence on nonsurgical and surgical interventions for the treatment of peri-implantitis and synthesize clinical guidelines based on high quality evidence. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until July 2023. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451056). A network meta-analysis was performed on data from randomized controlled trials that assessed nonsurgical and surgical interventions for the treatment of peri-implantitis. The interventions were ranked according to their efficacy using surface under the cumulative ranking (SUCRA) system. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to assess the level of certainty of evidence. RESULTS: A total of 45 articles were included in the quantitative analysis. The GRADE approach determined a moderate to high level of certainty of evidence. Among the nonsurgical interventions, mechanical debridement with adjunctive systemic antibiotics was significant in improving probing depth at 3 months and beyond 6 months, clinical attachment loss at 3 months, and clinical attachment loss beyond 6 months. Mechanical debridement with adjunctive topical antibiotics was significant in improving probing depth beyond 6 months, clinical attachment loss at 3 months, clinical attachment loss beyond 6 months, and radiographic bone loss beyond 6 months. Mechanical debridement with adjunctive photodynamic therapy was significant in improving probing depth beyond 6 months, clinical attachment loss at 3 months, clinical attachment loss beyond 6 months, and radiographic bone loss beyond 6 months. Mechanical debridement with adjunctive systemic antibiotics and photodynamic therapy was significant in improving probing depth beyond 6 months. Among surgical interventions, open flap debridement with implant surface decontamination and open flap debridement with decontamination and adjunctive photodynamic therapy were significant in improving probing depth at 3 months. CONCLUSIONS: Mechanical debridement with adjunctive systemic antibiotics or photodynamic therapy results in improved clinical outcomes.

Comparative effectiveness of types of denture adhesives in enhancing retention and function of complete dentures: a systematic review with network meta-analysis.

OBJECTIVES: The purpose of this systematic review with network meta-analysis was to assess the comparative efficacy of various types of denture adhesives in complete denture patients. MATERIAL AND METHODS: A search was conducted for trials published in Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until July 2023 (PROSPERO: CRD42023451045). A network meta-analysis was performed to assess the comparative efficacy of different denture adhesive types and ranked using the Surface Under the Cumulative Ranking (SUCRA) system. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the level of certainty of evidence. RESULTS: Seventeen articles were included in the quantitative analysis. Cream denture adhesives significantly increased bite force in both incisal region (RR = 7.63[95%CI: 3.34, 11.91]) (P < .05) as well as premolar and molar regions (RR = 33.66[95%CI: 15.15, 52.16]). Cream adhesives significantly improved retention of dentures as assessed by the reduced number of denture dislodgments (RR = -5.35[95%CI: -9.93, -0.77]) (P = 0.022), Kapur's index of retention (maxillary denture) (RR = 0.80[95%CI: 0.18, 1.42]) (P = 0.012) and Kapur's index of retention (mandibular denture) (RR = 1.27[95%CI: 0.67, 1.87]) (P < .05). Powder adhesives significantly increased premolar and molar bite force (RR = 36.00[95%CI: 16.20, 55.79]) (P < .05) and Kapur's index of retention (mandibular denture) (RR = 1.54[95%CI: 0.58, 2.49]) (P = 0.002). None of the adhesives were statistically significant for remaining outcomes. CONCLUSIONS: Cream and powder denture adhesives are effective in enhancing the retention of mandibular dentures (Kapur's index) and bite force in the premolar/molar region in complete denture wearers (moderate level of certainty of evidence). CLINICAL RELEVANCE: Cream and powder denture adhesives are effective in improving the retention and function of complete dentures.

Ventricular Tachycardia.

Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of ventricular tachycardia (VT) that is refractory to single dose anti-arrhythmic management. Background: Electrical storm, defined as three or more episodes of sustained VT, ventricular fibrillation, or appropriate shocks from an implantable cardioverter defibrillator within 24 hours,1 has a mortality rate up to 14% in the first 48 hours.2 Ventricular tachycardia may present in a heterogenous fashion, not only with stable versus unstable clinical presentations, but also with different electrocardiographic morphologies and etiologies.1 Understanding how to rapidly diagnose, treat, and utilize second or third-line treatments is vital in the setting of refractory ventricular tachycardia rather than relying on the success of first-line agents. Appreciation for what medications are readily available in your crash cart and medication dispensing cabinet is critical for timely management for refractory ventricular tachycardia. Educational Objectives: At the conclusion of the simulation session, learners will be able to: 1) identify the different etiologies of VT, including structural heart disease, acute ischemia, and acquired or congenital QT syndrome; 2) describe confounding factors of VT, such as electrolyte abnormalities and sympathetic surge; 3) describe how to troubleshoot an unsuccessful synchronized cardioversion, including checking equipment connections, increasing delivered energy, and changing pad placement; 4) compare and contrast treatments of VT based on suspected underlying etiology; 5) describe reasons to activate the cardiac catheterization lab other than occlusive myocardial infarction; and 6) identify appropriate disposition of the patient to the cardiac catheterization lab. Educational Methods: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of VT. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Research Methods: Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. Results: The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form3 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Twelve learners completed a feedback form. This session received 6 and 7 scores (consistently effective/very good and extremely effective/outstanding, respectively) other than three isolated 5 scores. The lowest average score was 6.67 for "Before the simulation, the instructor set the stage for an engaging learning experience." The highest average score was 7 for "The instructor helped me see how to improve or how to sustain good performance." The form also includes an area for general feedback about the case at the end. Illustrative examples of feedback include: "Excellent care and debrief." Specific scores are available upon request. Discussion: This is a cost-effective method for reviewing VT diagnosis and management. The case may be modified for appropriate audiences, such as describing what medications may be readily available in a free-standing emergency department or pre-hospital setting. Topics: Medical simulation, ventricular tachycardia, cardiac emergencies, dysrhythmias, cardiology, emergency medicine.

Functional involvement of septal miR-132 in extinction and oxytocin-mediated reversal of social fear.

Social interactions are critical for mammalian survival and evolution. Dysregulation of social behavior often leads to psychopathologies such as social anxiety disorder, denoted by intense fear and avoidance of social situations. Using the social fear conditioning (SFC) paradigm, we analyzed expression levels of miR-132-3p and miR-124-3p within the septum, a brain region essential for social preference and avoidance behavior, after acquisition and extinction of social fear. Here, we found that SFC dynamically altered both microRNAs. Functional in vivo approaches using pharmacological strategies, inhibition of miR-132-3p, viral overexpression of miR-132-3p, and shRNA-mediated knockdown of miR-132-3p specifically within oxytocin receptor-positive neurons confirmed septal miR-132-3p to be critically involved not only in social fear extinction, but also in oxytocin-induced reversal of social fear. Moreover, Argonaute-RNA-co-immunoprecipitation-microarray analysis and further in vitro and in vivo quantification of target mRNA and protein, revealed growth differentiation factor-5 (Gdf-5) as a target of miR-132-3p. Septal application of GDF-5 impaired social fear extinction suggesting its functional involvement in the reversal of social fear. In summary, we show that septal miR-132-3p and its downstream target Gdf-5 regulate social fear expression and potentially mediate oxytocin-induced reversal of social fear.

The Microbiome of Peri-Implantitis: A Systematic Review of Next-Generation Sequencing Studies.

(1) Introduction: Current evidence shows that mechanical debridement augmented with systemic and topical antibiotics may be beneficial for the treatment of peri-implantitis. The microbial profile of peri-implantitis plays a key role in identifying the most suitable antibiotics to be used for the treatment and prevention of peri-implantitis. This systematic review aimed to summarize and critically analyze the methodology and findings of studies which have utilized sequencing techniques to elucidate the microbial profiles of peri-implantitis. (2) Results: Fusobacterium, Treponema, and Porphyromonas sp. are associated with peri-implantitis. Veillonella sp. are associated with healthy implant sites and exhibit a reduced prevalence in deeper pockets and with greater severity of disease progression. Streptococcus sp. have been identified both in diseased and healthy sites. Neisseria sp. have been associated with healthy implants and negatively correlate with the probing depth. Methanogens and AAGPRs were also detected in peri-implantitis sites. (3) Methods: The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023459266). The PRISMA criteria were used to select articles retrieved from a systematic search of the Scopus, Cochrane, and Medline databases until 1 August 2023. Title and abstract screening was followed by a full-text review of the included articles. Thirty-two articles were included in the final qualitative analysis. (4) Conclusions: A distinct microbial profile could not be identified from studies employing sequencing techniques to identify the microbiome. Further studies are needed with more standardization to allow a comparison of findings. A universal clinical parameter for the diagnosis of peri-implantitis should be implemented in all future studies to minimize confounding factors. The subject pool should also be more diverse and larger to compensate for individual differences, and perhaps a distinct microbial profile can be seen with a larger sample size.

Detection, processing and reinforcement of social cues: regulation by the oxytocin system.

Many social behaviours are evolutionarily conserved and are essential for the healthy development of an individual. The neuropeptide oxytocin (OXT) is crucial for the fine-tuned regulation of social interactions in mammals. The advent and application of state-of-the-art methodological approaches that allow the activity of neuronal circuits involving OXT to be monitored and functionally manipulated in laboratory mammals have deepened our understanding of the roles of OXT in these behaviours. In this Review, we discuss how OXT promotes the sensory detection and evaluation of social cues, the subsequent approach and display of social behaviour, and the rewarding consequences of social interactions in selected reproductive and non-reproductive social behaviours. Social stressors - such as social isolation, exposure to social defeat or social trauma, and partner loss - are often paralleled by maladaptations of the OXT system, and restoring OXT system functioning can reinstate socio-emotional allostasis. Thus, the OXT system acts as a dynamic mediator of appropriate behavioural adaptations to environmental challenges by enhancing and reinforcing social salience and buffering social stress.

Comparative effectiveness of fiber and metal posts in the restoration of endodontically treated teeth: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Different varieties of fiber and metal intraradicular posts have been used for the restoration of endodontically treated teeth with insufficient sound tooth structure. Evidence on the comparative efficacy of posts in a clinical setting is insufficient to provide clear clinical guidelines and recommendations. PURPOSE: The purpose of this systematic review with network meta-analysis was to assess the comparative efficacy of fiber and metal posts used for the restoration of endodontically treated teeth. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until November 2022. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022384340). A network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of fiber posts and metal posts for the restoration of endodontically treated teeth. Subgroup analyses were performed to compare all the varieties of fiber and metal posts. The types of posts were ranked according to their efficacy using the Surface Under the Cumulative Ranking (SUCRA) system. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the level of certainty of evidence. RESULTS: Twenty-five articles were included in the quantitative analysis. Fiber posts (RR=0.15 [95% CI: 0.06, 0.33]) significantly prevented tooth fracture as compared with no posts. Prefabricated carbon fiber posts (RR=0.06 [95% CI: 0, 0.54]) ranked highest followed by custom glass fiber posts (RR=0.15 [95% CI: 0.04, 0.52]) and prefabricated glass fiber posts (RR=0.22 [95% CI: 0.07, 0.62]) in the outcome of tooth fracture. Metal posts (RR=0.24 [95% CI: 0.12, 0.46]) ranked higher than fiber posts (RR=0.39 [95% CI: 0.27, 0.56]) in the outcome of debonding. Custom gold alloy posts (RR=0.12 [95% CI: 0.03, 0.48]), prefabricated gold alloy posts (RR=0.04 [95% CI: 0.00, 0.87]), and prefabricated titanium posts (RR=0.21 [95% CI: 0.10, 0.45]) had higher rankings in the outcome of debonding or loss of retention of a post followed by custom glass fiber posts (RR=0.37 [95% CI: 0.21, 0.63]) and prefabricated glass fiber posts (RR=0.38 [95%CI: 0.25, 0.58]). Prefabricated glass fiber posts (RR=0.40 [95% CI: 0.20, 0.81]) had statistically significant differences in the outcome of secondary caries. The GRADE approach determined a moderate level of certainty of evidence. CONCLUSIONS: The use of a fiber post when indicated results in reduced risk of tooth fracture as compared with no post. Prefabricated carbon fiber posts, prefabricated glass fiber posts, and custom glass fiber posts reveal a lower risk of tooth fracture. Overall, the use of prefabricated glass fiber posts had a lower risk of tooth fracture, debonding, and secondary caries. However, more trials with longer follow-up periods are recommended to enhance the certainty of evidence.

Isolation and characterization of emerging Mpox virus from India.

Mpox (previously known as Monkeypox) has recently re-emerged, primarily through human-to-human transmission in non-endemic countries including India. Virus isolation is still considered as the gold standard for diagnosis of viral infections. Here, the qPCR positive skin lesion sample from a patient was inoculated in Vero E6 cell monolayer. Characteristic cytopathic effect exhibiting typical cell rounding and detachment was observed at passage-02. The virus isolation was confirmed by qPCR. The replication kinetics of the isolate was determined that revealed maximum viral titre of log 6.3 PFU/mL at 72 h postinfection. Further, whole genome analysis through next generation sequencing revealed that the Mpox virus (MPXV) isolate is characterized by several unique SNPs and INDELs. Phylogenetically, it belonged to A.2 lineage of clade IIb, forming a close group with all other Indian MPXV along with few from USA, UK, Portugal, Thailand and Nigeria. This study reports the first successful isolation and phenotypic and genotypic characterization of MPXV from India.

Comparative Efficacy and Safety of Interventions for the Treatment of Oral Lichen Planus: A Systematic Review and Network Meta-Analysis.

BACKGROUND: This systematic review and network meta-analysis aimed to assess comparative efficacy and safety of interventions to treat symptomatic, biopsy-proven oral lichen planus (OLP). METHODS: Search was conducted for trials published in Medline, Embase and Cochrane Central Register of Controlled Trials. Network meta-analysis was performed on data from randomized controlled trials that assessed efficacy and safety of interventions used in the treatment of OLP. Agents were ranked according to their effectiveness in treatment of OLP based on outcomes using surface under the cumulative ranking [SUCRA]. RESULTS: In total, 37 articles were included in the quantitative analysis. Purslane was clinically significant and ranked first in improving clinical symptoms [RR = 4.53; 95% CI: 1.45, 14.11], followed by aloe vera [RR = 1.53; 95% CI: 1.05, 2.24], topical calcineurin [RR = 1.38; 95% CI: 1.06, 1.81] and topical corticosteroid [RR = 1.35 95% CI: 1.05, 1.73]. Topical calcineurin demonstrated the highest incidence of adverse effects [RR, 3.25 [95% CI: 1.19, 8.86. Topical corticosteroids were significant in achieving clinical improvement of OLP with RR1.37 [95% CI: 1.03, 1.81]. PDT [MD = -5.91 [95% CI: -8.15, -3.68] and showed statistically significant improvement in the clinical score for OLP. CONCLUSIONS: Purslane, aloe vera and photodynamic therapy appear promising in treatment of OLP. More high-quality trials are recommended for strengthening the evidence. Although topical calcineurin is significantly efficacious in the treatment of OLP, significant adverse effects are a concern for clinical use. Based on the current evidence, topical corticosteroids are recommended for treatment of OLP owing to their predictable safety and efficacy.

Comparative effectiveness of interventions for the treatment of denture stomatitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Symptomatic denture stomatitis (DS) is a painful oral mucosal disorder that can impair quality of life in denture wearers. A complete cure of DS is difficult to achieve, and the most efficacious regimen to treat DS has not yet been conclusively established. PURPOSE: The purpose of this network meta-analysis was to assess the comparative efficacy of interventions used for the treatment of DS. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until February 2022 (PROSPERO Reg no: CRD42021271366). Network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of any form of intervention for the treatment of DS in denture wearers. Agents were ranked according to their effectiveness in the treatment of DS based on outcomes using surface under the cumulative ranking (SUCRA). RESULTS: A total of 25 articles were included in the quantitative analysis. Topical antifungal agents (risk ratio [RR]=4.37[95% confidence interval [CI]: 2.15,8.90), topical antimicrobial agents used along with systemic antifungal agents (RR=4.25[95% CI: 1.79,10.33]), systemic antifungal agents (RR=4.25[95% CI: 1.79,10.10]), photodynamic therapy (RR=4.25[95% CI: 1.75,8.98]), and topical plant products (RR=3.40[95% CI: 1.59,7.26]) were found to effectively improve DS. Microwave disinfection concurrently administered with topical antifungal agents (RR=7.38(95% CI: 2.75,19.81), microwave disinfection 7.38[95% CI: 2.75,19.81]), topical antifungal agents (RR=4.88[95% CI: 1.92,12.42]), topical plant products (RR=4.49[95% CI: 1.70,11.82]), systemic antifungal agents together with topical antimicrobial agents (RR=3.85[95% CI: 1.33,11.10]), topical antimicrobial agents (RR=3.39[95% CI: 1.17,9.81]), systemic antifungal agents (RR=3.37[95% CI: 1.21,9.34]), and photodynamic therapy or photochemotherapy (PDT) (RR=2.93[95% CI: 1.01,8.47]) were found to effectively resolve mycological DS. Topical antifungals ranked highest in the SUCRA ranking for clinical improvement, whereas microwave disinfection concurrently administered with topical antifungal agents ranked highest for mycological resolution. None of the agents demonstrated significant side effects except for topical antimicrobial agents which demonstrated altered taste and staining of oral structures. CONCLUSIONS: Available evidence suggests that topical antifungals, microwave, and systemic antifungals are effective in the treatment of DS, but confidence in these findings is low because of the limited number of studies and a high risk of bias. Additional clinical trials are needed on photodynamic therapy, topical plant products, and topical antimicrobials.

Comparative Efficacy of Different Amoxicillin Dosing Regimens in Preventing Early Implant Failure-A Systematic Review with Network Meta-Analysis.

This systematic review and network meta-analysis aimed to assess the comparative efficacy and safety of antibiotics to prevent early implant failure in patients undergoing dental implant surgery. METHODS: The review was registered in PROSPERO [CRD42022319385]. A search was conducted for trials published in Medline, Cochrane, PubMed, and Scopus. A network meta-analysis was performed on the data from randomized controlled trials. Agents were ranked according to their effectiveness based on outcomes (implant failure, prosthetic failure, postsurgical complications, and adverse effects) using the surface under the cumulative ranking [SUCRA]. RESULTS: A total of 15 articles were included in the quantitative analysis. When compared to the placebo, 2 g of amoxicillin given 1 h preoperatively (RR = 0.42 (95%CI: 0.27, 0.67)), 2 g of amoxicillin given 1 h preoperatively with postoperative 500 mg thrice for 5 days (RR = 0.36 (95%CI: 0.15, 0.87)), and post-operative amoxicillin with clavulanic acid 625 mg 3 times daily for 5 days (RR = 0.38 (95%CI: 0.16, 0.90)) were effective in reducing early implant failures. In addition, 2 g of amoxicillin given 1 h preoperatively (RR = 0.42 (95%CI: 0.25, 0.73)) was the only protocol that was significant in the pairwise meta-analysis results. However, sensitivity analysis, which excluded trials with a high risk of bias, showed that none of the protocols were statistically significant in reducing early implant failure. CONCLUSIONS: A single 2 g dose of preoperative amoxicillin significantly reduces early implant failure in healthy individuals. More high-quality trials are required to establish this recommendation, as the quality of this evidence is weak.

HDAC1-mediated regulation of GABA signaling within the lateral septum facilitates long-lasting social fear extinction in male mice.

Social anxiety disorder (SAD) is caused by traumatic social experiences. It is characterized by intense fear and avoidance of social contexts, which can be robustly mimicked by the social fear conditioning (SFC) paradigm. The extinction phase of the SFC paradigm is akin to exposure therapy for SAD and requires learning to disassociate the trauma with the social context. Learning-induced acetylation of histones is critical for extinction memory formation and its endurance. Although class I histone deacetylases (HDACs) regulate the abovementioned learning process, there is a lack of clarity in isoforms and spatial specificity in HDAC function in social learning. Utilizing the SFC paradigm, we functionally characterized the role of HDAC1, specifically in the lateral septum (LS), in regulating the formation of long-term social fear extinction memory. We measured a local increase in activity-inducing HDAC1 phosphorylation at serine residues of social fear-conditioned (SFC+) mice in response to the extinction of social fear. We also found that LS-HDAC1 function negatively correlates with acute social fear extinction learning using pharmacological and viral approaches. Further, inhibition of LS-HDAC1 enhanced the expression of the GABA-A receptor ß1 subunit (Gabrb1) in SFC+ mice, and activation of GABA-A receptors facilitated acute extinction learning. Finally, the facilitation of extinction learning by HDAC1 inhibition or GABA-A receptor activation within the LS led to the formation of long-lasting extinction memory, which persisted even 30 days after extinction. Our results show that HDAC1-mediated regulation of GABA signaling in the LS is crucial for the formation of long-lasting social fear extinction memory.

Transcriptome and chromatin alterations in social fear indicate association of MEG3 with successful extinction of fear.

Social anxiety disorder is characterized by a persistent fear and avoidance of social situations, but available treatment options are rather unspecific. Using an established mouse social fear conditioning (SFC) paradigm, we profiled gene expression and chromatin alterations after the acquisition and extinction of social fear within the septum, a brain region important for social fear and social behaviors. Here, we particularly focused on the successful versus unsuccessful outcome of social fear extinction training, which corresponds to treatment responsive versus resistant patients in the clinics. Validation of coding and non-coding RNAs revealed specific isoforms of the long non-coding RNA (lncRNA) Meg3 regulated, depending on the success of social fear extinction. Moreover, PI3K/AKT was differentially activated with extinction success in SFC-mice. In vivo knockdown of specific Meg3 isoforms increased baseline activity of PI3K/AKT signaling, and mildly delayed social fear extinction. Using ATAC-Seq and CUT&RUN, we found alterations in the chromatin structure of specific genes, which might be direct targets of lncRNA Meg3.

Neurobiology of the lateral septum: regulation of social behavior.

Social interactions are essential for mammalian life and are regulated by evolutionary conserved neuronal mechanisms. An individual's internal state, experiences, and the nature of the social stimulus are critical for determining apt responses to social situations. The lateral septum (LS) - a structure of the basal forebrain - integrates abundant cortical and subcortical inputs, and projects to multiple downstream regions to generate appropriate behavioral responses. Although incoming cognitive information is indispensable for contextualizing a social stimulus, neuromodulatory information related to the internal state of the organism significantly influences the behavioral outcome as well. This review article provides an overview of the neuroanatomical properties of the LS, and examines its neurochemical (neuropeptidergic and hormonal) signaling, which provide the neuromodulatory information essential for fine-tuning social behavior across the lifespan.

Development of an Online Asynchronous Clinical Learning Resource ("Ask the Expert") in Dental Education to Promote Personalized Learning.

This article describes the development and testing of an online asynchronous clinical learning resource named "Ask the Expert" to enhance clinical learning in dentistry. After the resource development, dental students from years 3 and 4 were randomly allocated to two groups (Group A-"Ask the Expert" and L-"lecturer-led"). All the students attempted a pre-test related to replacement of teeth in the anterior aesthetic zone. Group A (33 students) underwent an online case-based learning session of 60 minutes' duration without a facilitator, while Group L (27 students) concurrently underwent a case-based learning session of 60 minutes' duration with a lecturer facilitating the session. An immediate post-test was conducted followed by a retention test after one week. Student feedback was obtained. There was a significant increase in the test scores (maximum score 10) for both groups when comparing the pre-test (Group A-5.61 ± 1.34, Group L-5.22 ± 1.57) and immediate post-test scores (Group A-7.42 ± 1.34, Group L-8.04 ± 1.22; paired t-test, p < 0.001). However, no significant difference was observed in the test scores when comparing Group A to Group L for both the immediate post-test as well as the retention test (Group A-5.36 ± 1.29, Group L-5.33 ± 1.39 (independent sample t-test, p > 0.05). To conclude, adequately structured online asynchronous learning resources are comparable in their effectiveness to online synchronous learning in the undergraduate dental curriculum.

Increasing Reproducibility in Oral Microbiome Research.

Evidence on the role of the oral microbiome in health and disease is changing the way we understand, diagnose, and treat ailments. Numerous studies on diseases affecting the oral cavity have revealed a large amount of data that is invaluable for the advancements in diagnosing and treating these diseases. However, the clinical translation of most of these exploratory data is stalled by variable methodology between studies and non-uniform reporting of the data.Understanding the key areas that are gateways to bias in microbiome studies is imperative to overcome this challenge faced by oral microbiome research. Bias can be multifactorial and may be introduced in a microbiome research study during the formulation of the study design, sample collection and storage, or the sample processing protocols before sequencing. This chapter summarizes the recommendations from literature to eliminate bias in the microbiome research studies and to ensure the reproducibility of the microbiome research data.