Disrupting Maternal Behavior and Inducing Cannibalism Due to Valproic Acid: An Unexplored Insight.

Introduction: Valproic acid (VPA) is the most widely used chemical to develop the preclinical model of autism spectrum disorder (ASD). However, in addition to inducing autism, it causes different teratogenic effects like teeth malformation, tail kink, and abnormal body growth in offspring. So far, no study has explored VPA-induced maternal misbehavior, miscarriage, and maternal cannibalism. We aimed to determine the cannibalistic effects of VPA in pregnant female Wistar rats and VPA's influence on causing miscarriage frequency. Methods: Our study was conducted on pregnant Wistar rats. On gestation day (GD) 12.5, they were treated with VPA (600 mg/kg intraperitoneal) dissolved in saline at 250 mg/mL concentration. The observations were mean litter size, mean male/female pups, mean mortality, maternal cannibalism, mean number of pups alive, cannibalism of malformed pups, miscarriage, survival analysis of pups, and odds and risk ratio were calculated for deaths observed in both study (control and VPA-treated) groups. The study was conducted till the weaning period. Results: VPA-exposed pregnant females portrayed significantly decreased litter size (P<0.0001), significantly higher cannibalistic behavior (P=0.0023), and significantly higher cannibalism of malformed pups (P=0.0484) than the control group. VPA had caused complete pregnancy loss (miscarriage) in 5 pregnant females. Moreover, the VPA group's mortality percentage (P=0.0019) was significantly higher than the control group. Conclusion: Overall, VPA has marked teratogenic effects (anatomical and morphological changes in offspring) with maternal behavior disruption, which causes cannibalism in Wistar female rats. The current manuscript findings can aid in investigating the novel mechanisms involved in maternal behavior disruption during the development of the VPA autism model.

Unleashing the therapeutic role of cannabidiol in dentistry.

Cannabidiol (CBD) found in Cannabis sativa is a non-psychoactive compound which is capable of binding to CB1 and CB2 receptors. CBD has recently gained interest in dentistry although it has not been explored sufficiently yet. The therapeutic effects of CBD include anti-inflammatory, analgesic, antioxidant, biological and osteoinductive properties. The aim of this review is to highlight these effects with respect to various oral conditions and shed light on the current limitations and prospects for the use of CBD in maintaining oral health.

Assessment of mechanical allodynia in healthy teeth adjacent and contralateral to endodontically diseased teeth: a clinical study.

Objectives: The present study investigated the prevalence of mechanical allodynia (MA) in healthy teeth adjacent and contralateral to endodontically diseased teeth. Materials and Methods: This cross-sectional study included 114 patients with symptomatic irreversible pulpitis and apical periodontitis in permanent mandibular first molars who possessed healthy teeth adjacent and contralateral to the endodontically diseased tooth. The mechanical sensitivity of the teeth was determined by percussion testing. The presence or absence of pain on percussion in the teeth adjacent and contralateral to the endodontically diseased tooth and the tooth distal to the contralateral symmetrical tooth was recorded according to coding criteria. The prevalence of MA was computed as a percentage, and binary logistic regression analysis was done. The Fisher exact test and Mann-Whitney U test were used for binary and ordinal data. Results: Age and sex did not influence the prevalence of MA. An increased prevalence of MA was found in patients with higher levels of spontaneous pain (p < 0.001). The prevalence of allodynia was 57% in teeth adjacent to endodontically diseased teeth and 10.5% in teeth contralateral to endodontically diseased teeth. In addition, on the ipsilateral side, there were more painful sensations distal to the diseased tooth than mesially. Conclusions: Despite being disease-free, teeth adjacent and contralateral to endodontically diseased teeth exhibited pain on percussion. There was a direct association between the severity of the patient's pain and the presence of MA.

Comparing the Efficacy of 5% EMLA Cream and 20% Benzocaine Gel on Gingival Tissue Surrounding Non-Carious Cervical Lesions for Reduction of Pain Following Rubber Dam Clamp Placement: A Split-Mouth Randomized Clinical Trial.

Aim The aim of this study was to evaluate the effectiveness of 5% eutectic mixture of local anesthetics (EMLA) cream and 20% benzocaine gel in reduction of pain during rubber dam clamp placement in the treatment of non-carious cervical lesions (NCCLs). Methodology In this split-mouth single-blind randomized clinical trial, 50 adult participants were selected from the outpatient department. The test group was treated using 5% EMLA cream for three minutes, and visual analog scale (VAS) scores were recorded. The comparison group was treated using 20% benzocaine gel and procedure was repeated as that in the test group. After recording the VAS scores, NCCLs in both the groups were restored using composite restoration. Results In the included 50 participants, 70% were males, with an age group of 31-67 years. The mean VAS score at 3 minutes in EMLA group was significantly lower than that in benzocaine group. Conclusion Application of 5% EMLA cream for 3 minutes showed greater pain reduction during rubber dam clamp placement as compared to 20% benzocaine gel in adult patients with NCCLs.

Review on Hyaluronic Acid Functionalized Sulfur and Nitrogen Co-Doped Graphene Quantum Dots Nano Conjugates for Targeting of Specific Type of Cancer.

Many people lose their lives to cancer each year. The prevalence of illnesses, metabolic disorders, high-risk infections, and other conditions has been greatly slowed down by expanding scientific research. Chemotherapy and radiation are still the initial lines of treatment for cancer patients, along with surgical removal of tumors. Modifications have been made in chemotherapy since medicines frequently have substantial systemic toxicity and poor pharmacokinetics and still do not reach the tumor site at effective concentrations. Chemotherapy may now be administered more safely and effectively thanks to nanotechnology. Nanotechnology-based graphene quantum dots (GQDs) are very applicable in breast cancer detection, as a drug delivery system, and in the treatment of breast cancer because of their physical and chemical properties, lower toxicity, small size, fluorescence, and effective drug delivery. This paper analyzes the GQDs as cutting-edge platforms for biotechnology and nanomedicine also its application in drug delivery in cancer. It shows that GQDs can be effectively conjugated with hyaluronic acid (HA) to achieve efficient and target-specific delivery.

Prevalence of anti-HLA antibodies in COVID-19 convalescent plasma donors: an Indian experience.

BACKGROUND: COVID-19 convalescent plasma is one of the experimental therapies used widely in moderately sick COVID-19 patients. However, there are a few risks involved in plasma transfusion; notably, transfusion-related acute lung injury (TRALI) caused by antibodies against human leukocyte antigens (HLA). This study was designed to assess the prevalence of anti-HLA antibodies in convalescent plasma donors using the single antigen bead method. STUDY DESIGN AND METHODS: This was a hospital-based observational study of consecutive plasma donors. A total of 252 samples were screened for anti-HLA Class I and Class II antibodies using the microbead assay with the identification of anti-HLA Ab in positive samples being performed using a single antigen bead assay. Luminex-based normalized background cutoff ratios of 10.8 for Class I and 6.9 for Class II and mean fluorescence intensity cutoffs of 2500 for Class I and 1500 for Class II were used for screening and the single bead assay, respectively. RESULTS: Of 252 screened samples, 28 (11.1 %) were positive for Class I, Class II or both Class I and Class II anti-HLA antibodies in donors with no history of a previous immunizing event. Moreover, 20/252 (7.9%) donors without any history of prior immunization had specific anti-HLA antibodies of Class I or Class II or both by the single bead assay. CONCLUSIONS: The high prevalence of anti-HLA antibodies in our cohort of donors raises an urgent and immediate need for anti-HLA antibody screening in all convalescent plasma donors for safe therapy of COVID-19 patients.

An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis and regression. Propranolol is the mainstay of treatment for IH. It inhibits hemangioma vessel formation via a ß-adrenergic receptor independent off-target effect of its R(+) enantiomer on the endothelial specific transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss of SOX18 function confirmed R(+) propranolol mode of action on the MVP. Functional validation in preclinical IH models revealed that statins - targeting the MVP - are potent inhibitors of hemangioma vessel formation. We propose a novel SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. Our findings reveal novel pleiotropic effects of beta-blockers and statins acting on the SOX18-MVP axis to disable an endothelial specific program in IH, which may impact other scenarios involving pathological vasculogenesis and angiogenesis.

Evaluation of bone apposition on surface modified titanium implant in experimental animal model: A systematic review and meta-analysis.

Purpose: To evaluate the response of peri-implant bone to smooth (machined) surface and surface-modified dental implants in healthy experimental animal models. Materials and Methods: Systematic electronic search was done for using PUBMED, SCOPUS, WEB OF SCIENCE, and EMBASE databases for potentially relevant records from the last 20 years. Duplicate screening and data extraction were performed to formulate the evidence tables and meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The outcome criteria were: 1. Bone Implant Contact (BIC) in percentage, 2. Removal Torque Values (RTV) in Ncm, 3. Implant stability Quotient (ISQ), Quality assessment was done using the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and SYRCLE RoB (Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias) tool. Results: Results were expressed as pooled mean difference for the respective groups viz. sandblasted and acid etched, laser modified, acid etched and anodized surface. The surface modified implants revealed somewhat higher BIC over machined surface (P < 0.01). Forest plot were drawn for all the outcome variables. Conclusions: Within the limitations of this study, the authors found a higher degree of osseointegration pertaining to bone to implant interface, RTV, and implant stability quotient (ISQ) with surface modified procedures which seemed to promote bone formation around peri-implant tissue during the early stages of healing. After analyzing all 37 included publications for the outcome of interest (BIC%, RTV, ISQ), a positive outcome was obtained for both subtractive and additive implant surface modifying procedures over machined implant surfaces when the data were pooled together. More advanced research work on healthy animal models needs to be investigated to review the impact of surface modifications on dental implant osseointegration.

Indian Society of Periodontology Good Clinical Practice Recommendations for Peri-implant Care.

Current implant therapy is a frequently employed treatment for individuals who have lost teeth, as it offers functional and biological advantages over old prostheses. Concurrently, active exploration of intervention strategies aims to prevent the progression of peri-implant diseases and manage the existing peri-implant tissue damage. Indian Society of Periodontology has recognized the need for systematic documents to update the everyday clinical practice of general dental practitioners and has provided evidence-based consensus documents, namely good clinical practice recommendations from time to time to raise the oral health-related awareness and standards of oral health-care delivery across the country. The current clinical practice recommendations focused on peri-implant care to bridge the gap between academic theory and clinical practice by compiling evidence-based suggestions for preventing and treating peri-implant diseases. Twenty-eight subject experts across the country prepared these recommendations after a thorough literature review and group discussions. The document has been prepared in three sections covering peri-implant health and maintenance, peri-implant mucositis, and peri-implantitis. It will be a quick and concise reference for oral implant practitioners in patient management. The guidelines provide distinct definitions, signs, and symptoms, treatment required; recall visit specifications for plausible clinical case situations, and home-care recommendations regarding maintaining peri-implant health. The document advocates combined efforts of oral implant practitioners and the population at large with evidence-based, integrated, and comprehensive peri-implant care. By providing accessible, applicable guidance, these guidelines would empower dental professionals to uphold the well-being of implant patients and ensure the long-term success of implant therapy.

Comparative evaluation of increase in temperature on the external root surface of teeth during retrieval of broken NiTi instrument using two ultrasonic tips and two power settings: An in vitro study.

Context: An unfavorable event that can hinder endodontic treatment and affect the outcome of root canal treatment is the separation of endodontic instruments. Endodontic instrument separation can occur due to clinical or metallurgical factors. Friction between the ultrasonic tip and the remaining dentin generates heat, which is subsequently transferred to the external root surface. Elevated temperatures exceeding 10°C above body temperature for more than a minute may result in injury to periodontal or bone tissue. Aim: The aim of this study was to evaluate and compare temperature rise on the external root surface of teeth during retrieval of broken NiTi instrument using two different ultrasonic tips and two power settings. Materials and Methods: In each group, a sample size of 8 was sufficient to attain a statistical power exceeding 90%, enabling the detection of a minimum mean difference of 0.9204 (delta) through a one-way ANOVA test at a 95% confidence level (alpha 0.05). After access opening and working length determination, samples were randomly distributed into two groups - Group 1 (A and B) - ProUltra tip at high and low power settings and Group 2 (A and B) - Cric Dental IR3 at high and low power settings. The temperature rise was measured using K-type thermocouple thermometer. The comparisons were analyzed using the Kruskal-Wallis test with pairwise comparisons using the Dunn's test. Results: Group 1A and Group 1B resulted in lower heat generation compared to Group 2A and 2B and its difference was statistically significant (P < 0.05). Minimum temperature rise is seen in the ProUltra group at lower power settings (Group 1A) at the apical level and maximum temperature rise is seen in the Cric Dental IR3 group at higher power settings (Group 2B) at the middle third level. Conclusion: It was found that there is a significant temperature rise seen when ultrasonic tips are used for the retrieval of separated files, especially at higher power settings. The ProUltra tip demonstrated the lowest temperature rise at lower power settings, particularly at the apical level, whereas the IR3 Cric Dental tip exhibited the highest temperature rise, notably at higher power settings and the middle third level.

An Evaluation of Random Donor Platelets Prepared from Overnight Stored Buffy Coat Method: A Better Alternative to the 6-h Restriction.

Preparing maximum platelets from all daily blood donations is essential to maintain adequate stock of platelets that may be feasible by storing buffy coat overnight. The overnight stored buffy coat method is prevalent in Europe and was not studied much in India. Therefore, a comparative study was planned to compare RDPs prepared from fresh and overnight stored buffy coat methods. In this study total of eighty RDPs were prepared. Forty RDPs were prepared by each method by matching similar platelet counts in whole blood in pairs and avoiding other bias. Quality analysis was done in various hematological, biochemical, metabolic, and activation parameters and with National guideline. RDPs prepared by the overnight stored buffy coat method had statistically higher mean platelet counts, lesser WBC contamination, lesser glucose concentration, higher lactate concentration, lesser pH, and higher MPV & PDW than RDPs prepared by the fresh buffy coat method. P selectin levels were lesser in the overnight stored category. The platelet yield in RDPs (extraction from the whole blood) was more in the overnight stored category. Compared with the national guideline, 87.5% of units passed the quality criteria in the fresh category compared to 100% of units in the overnight category. RDPs prepared from overnight stored buffy coats not only had better quality parameters but also were in a less activated state. Because of better quality and feasibility in blood centers, the overnight stored buffy coat method may also be used along with the traditional preparation method.

Nicotine prevalence among youth of rural Jaipur, Rajasthan.

Background: Children are more sensitive to tobacco advertisements than adults. The World Health Organization (WHO) reported that tobacco use has doubled in the past four decades particularly among the youth. Smoking among teenagers is an issue that affects countries worldwide. Objective: This study identified the prevalence of tobacco consumption among youth of rural Jaipur. We also studied, their age of initiation of tobacco and their correlation with the income and occupation of parents. Method: Community based cross-sectional type of study was conducted on youth of 15-24 years of age in 30 clusters in the Vatika, Jaipur. Cluster sampling technique was adopted. A semi-structured pretested and predesigned questionnaire was used for data collection. The inter-personal communication technique was used maintaining full confidentiality. All the results were transferred onto Microsoft excel sheet and evaluated statistically. Results: Out of 420 youths, 79.0% youths consumes nicotine in any form. More male subjects (90.9%) consume nicotine than females (62.8%) highly significantly. 33.1% youths started nicotine consumption <12 years. Youths from more income family(63.6%), illiterate father (76.2%), illiterate mother (74.4%), father having farming as occupation (67.2%), consumes more nicotine. more (88.6%) of youths consume nicotine with their friends. 58.1% parents oppose their children. Conclusion: The prevalence of nicotine intake was higher in boys than girls and majority of them consumes nicotine in any form gutka or beedi-cigarette. The reasons for such high dependence of nicotine according to the youth were lack of knowledge of the ill effects of nicotine intake and peer pressure. However, majority of the youth did not want to quit nicotine consumption.

Is There a Need for an Exogenous Activator Along with PRP for Early Knee Osteoarthritis? A Triple-Blinded Randomized Control Trial.

Background: In addition to other variables associated with PRP injections for Knee Osteoarthritis (OA), some confusion exists about the role of exogenous activators. The current study looks at matched groups getting PRP injections with or without activator (Calcium gluconate) in early knee OA patients. Methods: Patients of early OA knee meeting inclusion criteria were randomly divided into 2 groups; Group A (43 patients) received 8 ml PRP injection alone, and Group B (48 patients) received 8 ml PRP along with 2 ml Calcium gluconate as activator. The patients were evaluated at baseline, 6 weeks, 3 months and 6 months for WOMAC Pain and Total WOMAC scores; secondary variables assessed were VAS score and patient satisfaction. Results: The baseline characteristics of both groups were comparable. Leucocyte-depleted PRP with 5 times concentration and average absolute platelet numbers of 7.144 billion per knee was injected. Mean Pain WOMAC scores decreased in both groups from baseline (group A-8.68, group B-9.09) to final follow-up (group A-4.67, group B-5.11). Similarly, Mean Total WOMAC scores decreased from baseline (group A-37.81, group B-37.41) to (group A-21, group B-21.36) at the final follow-up in both groups. There was no significant difference between both groups, and both showed similar trends. Similar findings were noted for VAS scores. Patient satisfaction was also not different (group A, 90.69%, group B, 89.58%) at the end of 6 months. Conclusion: Our study concluded doubtful role of adding exogenous activator to PRP preparation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01159-7.

Unlocking the Therapeutic Potential: Sitagliptin's Multifaceted Approach in Drug-Resistant Epilepsy through a Novel Mechanism Inhibiting Protein Kinase C-γ and a Long-Term Potentiation Pathway.

Drug-resistant epilepsy is a prominent challenge in chronic neurological disorders. Valproate, commonly used to treat epilepsy, can fail due to various side effects and interactions, necessitating the exploration of alternative treatments. Our study primarily investigated sitagliptin's potential as a therapeutic agent for drug-resistant epilepsy. Employing computational modeling and enzyme assay testing, three lead compounds, emixustat, sitagliptin, and distigmine bromide, were evaluated against the target enzyme protein kinase C-γ. In vivo, experiments on a pentylenetetrazolium-induced lamotrigine-resistant epilepsy model were conducted to test sitagliptin's antiseizure effects, compared with the standard phenobarbital treatment. Emixustat and sitagliptin showcased strong inhibitory properties, while distigmine bromide was less effective in the enzyme assay. Mechanistic insights revealed sitagliptin's ability to modulate the seizure grade and first myoclonic jerk latency via oxidative stress markers, like reduced glutathione and glutathione peroxidase emphasizing its antioxidative role in epilepsy. Additionally, it demonstrated anti-inflammatory effects by significantly reducing proinflammatory markers interleukin-1ß and interleukin-6. The modulation of key genes of the long-term potentiation pathway, particularly protein kinase C-γ and metabotropic glutamate receptor 5, was evident through mRNA expression levels. Finally, sitagliptin showed potential neuroprotective properties, limiting pentylenetetrazolium-induced neuronal loss in the hippocampal region. Collectively, our findings suggest sitagliptin's multidimensional therapeutic potential for drug-resistant epilepsy specifically via a long-term potentiation pathway by inhibiting protein kinase C-γ.

Successful Management of Anomalous Lipton R-III Right Coronary Artery Chronic Total Occlusion.

Chronic total occlusion (CTO) of the coronary artery is a subset where cardiologists confront technical challenges most of the time during percutaneous coronary intervention (PCI). A congenital coronary anomaly is considered a critical challenge, especially when accompanied by CTO lesions. We report a case of a 64-year-old hypertensive and chronic smoker male who presented to our tertiary care center with chief complaints of Canadian Cardiovascular Society II angina. Coronary angiography revealed proximal right coronary artery CTO in a patient with an anomalous origin of coronary arteries arising from the right single sinus "Lipton R-III" which was managed successfully through PCI.

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain.

Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn. We found that macrophage and neutrophil recruitment closely mirrored the kinetics of pain development and identified cell-type-specific transcriptional programs associated with pain and its resolution. Using a comprehensive list of potential interactions mediated by receptors, ligands, ion channels and metabolites to generate injury-specific neuroimmune interactomes, we also uncovered that thrombospondin-1 upregulated by immune cells upon injury inhibited nociceptor sensitization. This study lays the groundwork for identifying the neuroimmune axes that modulate pain in diverse disease contexts.

Ultrafast Removal of Thorium and Uranium from Radioactive Waste and Groundwater Using Highly Efficient and Radiation-Resistant Functionalized Triptycene-Based Porous Organic Polymers.

Thorium (Th) and uranium (U) are important strategic resources in nuclear energy-based heavy industries such as energy and defense sectors that also generate significant radioactive waste in the process. The management of nuclear waste is therefore of paramount importance. Contamination of groundwater/surface water by Th/U is increasing at an alarming rate in certain geographical locations. This necessitates the development of strategic adsorbent materials with improved performance for capturing Th/U species from radioactive waste and groundwater. This report describes the design of a unique, robust, and radiation-resistant porous organic polymer (POP: TP-POP-SO3NH4), which demonstrates ultrafast removal of Th(IV) (<30 s)/U(VI) (<60 s) species present in simulated radioactive wastewater/groundwater samples. Thermal, chemical, and radiation stabilities of these POPs were studied in detail. The synthesized ammoniated POP revealed exceptional capture efficiency for trace-level Th (<4 ppb) and U (<3 ppb) metal ions through the cation-exchange mechanism. TP-POP-SO3NH4 shows a significant sorption capacity [Th (787 mg/g) and U (854 mg/g)] with an exceptionally high distribution coefficient (Kd) of 107 mL/g for Th. This work also demonstrates a facile protocol to convert a nonperforming POP, by simple chemical modifications, into a superfast adsorbent for efficient uptake/removal of U/Th.