Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.

Impact of tofogliflozin on hepatic outcomes: a systematic review.

PURPOSE: Studies have demonstrated a high prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients. The aim was to review the effect of tofogliflozin on hepatic outcomes in T2DM patients. METHODS: A literature search in PubMed, Science Direct and Cochrane Central Register of Controlled Trials was conducted for randomised clinical trials of tofogliflozin by applying predetermined inclusion and exclusion criteria. RESULTS: A total number of four randomised clinical trials, including 226 subjects, were included in the review. There was a significant decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in the tofogliflozin group as compared to the control or active comparator groups. Additionally, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) levels were also significantly decreased in the tofogliflozin group. However, no significant difference was observed in levels of adiponectin. CONCLUSION: Overall, an improvement in levels of hepatic parameters was observed in T2DM patients with concurrent liver disorders. However, a large number of clinical trials are needed to prove the efficacy of tofogliflozin on hepatic outcomes in patients with T2DM.

Efficacy and safety of nelarabine in patients with relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis.

Nelarabine is approved for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients who relapse following at least two different chemotherapy regimens. Previous studies have evaluated the efficacy and safety of nelarabine with chemotherapy in the treatment of R/R T-ALL. However, the results are inconsistent. This review aimed to summarize findings on efficacy and safety data in R/R T-ALL patients administered with the drug nelarabine. The present review conducted a comprehensive search of MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until 15 January 2022. Thirteen studies fulfilled the eligibility criteria with a total of 2508 patients. The efficacy of nelarabine was studied in terms of complete remission (CR) and partial remission (PR). Included studies reported overall random-effects pooled prevalence of CR and PR were 37.2 (95% CI: 22.8, 51.5) and 10.2 (95% CI: 4.9, 15.5), respectively. Most common adverse events associated with nelarabine were neutropenia, thrombocytopenia, fatigue, infections, and reversible peripheral neuropathy. Nelarabine is being used as salvage therapy as a bridge to hematopoietic stem cell transplantation and the findings of this meta-analysis indicate that it is an effective and safe treatment to be used in addition to the first-line treatment for R/R T-ALL.

Gestational Age at Delivery and Neonatal Outcomes among Infants with Gastroschisis in the Children's Hospitals Neonatal Consortium (CHNC).

OBJECTIVE: The effect of gestational age (GA) on gastroschisis outcomes is unclear and delivery timing varies in practice. We aimed to correlate clinical outcomes of infants with gastroschisis and GA at delivery in the Children's Hospitals Neonatal Consortium (CHNC). STUDY DESIGN: This was a retrospective multicenter cohort study of infants with gastroschisis admitted to CHNC neonatal intensive care units (NICUs) from 2010 to 2016. Patients were categorized by GA: 32 to 346/7, 35 to 366/7, and ≥37 weeks. Respiratory and feeding interventions, mortality, length of stay, and common complications were compared. RESULTS: In 2021 for patients with gastroschisis, median GA at delivery was 36.3 weeks (interquartile range [IQR] 35.1, 37.3) and mean birth weight 2,425 g (IQR 2,100, 2,766). Overall mortality was low and there was no difference across GA groups. Infants <35 weeks' gestation had the greatest need for respiratory and feeding interventions. Complications such as medical necrotizing enterocolitis (NEC), cholestasis, and central line-associated blood stream infection were less common in infants ≥37 weeks. Feeding initiation and full feeds were earliest in term infants, compared with infants between 35 and 366/7 weeks, and longest in infants <35 weeks. Prematurity had a significant negative association with breast milk exposure. Enteral feeding tube support at discharge increased with prematurity. Compared with term, infants born between 35 and 366/7 weeks' gestation had a higher incidence of medical NEC and lower exposure to mother's milk at discharge but the need for respiratory interventions or tube feeding at discharge was similar. CONCLUSION: Premature infants with gastroschisis had more neonatal complications including respiratory interventions, longer NICU stay, longer time to full enteral feeds, and higher need for tube feeds at discharge as compared with those delivered at term. Differences were greatest for those <35 weeks GA. While overall mortality remains low, these results provide additional information about GA at birth in gastroschisis, with no evidence of benefit from preterm delivery. KEY POINTS: · Respiratory support was greatest for those with <35 weeks gestation.. · NEC and cholestasis increase with prematurity.. · Term infants have better feeding outcomes..

Embelin ameliorates cognitive dysfunction and progression of kindling in pentylenetetrazol-induced kindling in mice by attenuating brain inflammation.

OBJECTIVE: This study was conducted to evaluate the effect of embelin (EMB) on various epileptic models and related brain inflammation. METHODS: Male Swiss albino mice were administered EMB (5, 10, and 20 mg/kg/p.o.) in acute and chronic study for 7 days and 35 days, respectively. Acute study included increasing current electroshock (ICES) and pentylenetetrazol (PTZ)-induced seizure test. Step-down latency (SDL) and forced swim test (FST) were performed to evaluate cognitive functions and depression-like behavior, respectively. Chronic study included PTZ-induced kindling. Levels of inflammatory biomarkers, namely interleukin-1 beta (IL-1ß), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were estimated in the hippocampus and cortex of the kindled brains by ELISA technique. Further, neurotransmitters (NTs), namely gamma aminobutyric acid (GABA), glutamate, and dopamine, were estimated by using validated liquid chromatography-mass spectrometry (LC-MS) method followed by ultra-high-performance liquid chromatography (UHPLC). RESULTS: Embelin (EMB) treatment increased the seizure threshold to hind limb extension (HLE) in the ICES test and decreased the seizure scores in the kindling experiment. Significantly low levels of IL-1ß, IL-1Ra, IL-6, and TNF-α were observed in the hippocampus of PTZ + EMB (10 and 20 mg/kg)-treated groups compared with PTZ+ vehicle-treated group. Significantly lower levels of IL-1Ra, IL-6, and TNF-α compared with PTZ+ vehicle-treated group were observed in the cortex of PTZ + EMB (10 and 20 mg/kg)-treated groups, while IL-1ß levels were found to be significantly lower only in the cortex of PTZ + EMB (20 mg/kg)-treated group. Increased levels of dopamine and GABA and decreased levels of glutamate in both hippocampus and cortex were observed in EMB + PTZ-treated groups compared with vehicle + PTZ-treated group. Latency of step down was found to be increased and immobility time in FST was decreased in EMB + PTZ groups compared with vehicle + PTZ group. CONCLUSION: Embelin suppressed epileptogenesis in the kindled mice via neurochemical modulation of neurotransmitters and inhibiting the inflammatory pathway. Further, EMB was also observed to be protecting the kindled animals from cognition and depression-like behavior.

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis.

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease. METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. CONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients.

Cross-cultural adaptation and psychometric properties of the Hindi version of Child Perception Questionnaire (CPQ11-14 ) in school children.

BACKGROUND: There is a need to validate OHRQoL measures in Hindi to assess the OHRQoL of Indian children. AIM: To develop a Hindi version of the CPQ11-14 and to appraise its validity and reliability for use among North Indian children aged 11-14 years. DESIGN: The cross-culturally adapted Hindi version of CPQ11-14 was achieved by forward translation, backward translation, committee review, and pretesting. A total of 1000 children were recruited from schools, chosen by two-stage cluster random sampling technique. After completing the self-administered questionnaire CPQ11-14 by the child, oral examination was conducted using decayed/missing/filled teeth (DMFT) index, malocclusion index, and Dean's fluorosis index. Test-retest reliability was checked on 100 participants after one week. RESULTS: The floor effect was present in 3.6% individuals, and there was no ceiling effect. Cronbach's alpha for the overall CPQ11-14 scale was 0.963. Intra-class correlation (ICC) coefficient was 0.952 for the entire scale. Cronbach's alpha value for test-retest was 0.918. There was a non-significant change in domain-level and overall median CPQ11-14 scores with an increase in DMFT scores. For malocclusion and fluorosis, there was a statistically significant increase in overall and domain-level scores with increased severity scores. CPQ11-14 and individual domains significantly correlated with both the global questions. CONCLUSION: Hindi version of CPQ11-14 is a reliable scale to assess OHRQoL in Hindi speaking 11- to 14-year-old children.

A Comparative Quantitative Assessment of Salivary Iga and Alpha Amylase in Caries Free and Caries Active Children.

OBJECTIVES: The aim of the study was to assess the salivary IgA (immunoglobulin A) and alpha amylase levels in the unstimulated whole saliva samples of caries-free and caries-active children and correlate it with the caries status and age. STUDY DESIGN: The salivary IgA and amylase was investigated in 100 children in the range of 8-12 years divided in two groups, control group (DMFT and/or deft = 0) and study group (DMFT/deft score ≥5). The salivary IgA was measured using kit based on two-site sandwich enzyme immunoassay principle and amylase was estimated using the vitro amyl slides. RESULTS: The mean salivary IgA and amylase levels in the saliva of the children in the control group was found to be significantly increased (p=.001 and p=.014 respectively) whereas the relationship between salivary IgA and amylase levels in the saliva of the children was found to be insignificant with the age (p=.392 and p=.306 respectively). CONCLUSIONS: The results indicated that salivary IgA and amylase levels in saliva increased significantly in caries free children and the level of salivary IgA and alpha amylase has no significant relation with the age of the children.

Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine.

In view of well-evidenced antiepileptic effects of melatonin and few reports of anticonvulsant action of agomelatine, the present study investigated whether agomelatine protects against pentylenetetrazole (PTZ)-induced kindling in mice and kindling-associated oxidative stress, depression, and impairment of spatial memory. In order to explore whether effects are mediated by melatonergic or serotonergic mechanisms, 1-(m-chlorophenyl) piperazine (mCPP), selective 5HT2c receptor agonist and luzindole, melatonergic receptor antagonist, were taken as pharmacological tools. In view of few hepatotoxic reports on agomelatine, the study evaluated effects on hepatic enzyme levels. Swiss strain albino mice were injected with PTZ (25mg/kg, i.p.) once every two days for 5weeks to induce kindling. The effects of agomelatine (10mg/kg, p.o.) alone and in combination with luzindole (2.5mg/kg, i.p.) or mCPP (7mg/kg, i.p.) on seizure severity during induction and % incidence of animals kindled at the end of 5weeks were recorded. Modified forced swim test was used for studying depression-like behavior while spontaneous alternation behavior was used for studying effects on spatial memory. Serum AST and ALT concentrations, cortical and hippocampal malondialdehyde, and reduced glutathione were measured. Agomelatine 10mg/kg, p.o. effectively delayed development of kindling, reduced seizure severity, and decreased % incidence. Luzindole reversed the protective effects of agomelatine while mCPP failed to show such a reversal, indicating melatonergic (and not serotonergic) mechanisms in the observed effects. Agomelatine also showed antioxidant effects that can partially contribute to its anticonvulsant action. In addition, it alleviated PTZ-kindling-associated behavioral despair and favorably modulated liver enzymes. Its effects on improvement of kindling-associated spatial memory could possibly be related to its effects on locomotor activity. Agomelatine, thus, could be explored as an adjunct to antiepileptic drugs for seizure control and for alleviating epilepsy-associated depression.

Intranasal pitavastatin attenuates seizures in different experimental models of epilepsy in mice.

This study was carried out to evaluate the effect of intranasal pitavastatin (PVS) on pentylenetetrazole (PTZ)-induced seizures, increasing current electroshock (ICES) seizures, and status epilepticus in mice. Intranasal PVS, 0.5 and 1.0mg/kg, showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control; however, the effects were dose-dependent and were more significant at higher dose. Further, intranasal PVS (1.0mg/kg) but not intravenous PVS (50.0mg/kg) showed effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal PVS (1.0mg/kg), thus making it a prospective therapeutic approach for acute seizures and status epilepticus.

Resveratrol suppressed seizures by attenuating IL-1ß, IL1-Ra, IL-6, and TNF-α in the hippocampus and cortex of kindled mice.

OBJECTIVE: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice. METHOD: Swiss albino mice were administered RESV (10, 20 and 40 mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25 mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1ß, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-α were assessed in the hippocampus and cortex of the kindled animals. RESULTS: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1ß, IL1-Ra, IL-6, and TNF-α in kindled mice. CONCLUSION: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.

Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro.

AIM: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors can not only lower blood glucose levels, but also alleviate cardiac remodeling after myocardial ischemia and hypertension. In the present study, we investigated the effects of a DPP-4 inhibitor (linagliptin) and a GLP-1 activator (liraglutide) on glucose- and angiotensin II (Ang II)-induced collagen formation and cytoskeleton reorganization in cardiac fibroblasts in vitro, and elucidated the related mechanisms. METHODS: Cardiac fibroblasts were isolated from the hearts of 6-week-old C57BL/6 mice, and then exposed to different concentrations of glucose or Ang II for 24 h. The expression of fibrotic signals (fibronectin, collagen-1, -3 and -4), as well as ERK1/2 and NF-κB-p65 in the fibroblasts was examined using Western blotting assays. F-actin degradation was detected under inverted laser confocal microscope in fibroblasts stained with Rhodamine phalloidin. RESULTS: Glucose (1-40 mmol/L) and Ang II (10-8-10-5 mol/L) dose-dependently increased the expression of fibronectin, collagens, phospho-ERK1/2 and phospho-NF-κB-p65 in cardiac fibroblasts. High concentrations of glucose (≥40 mmol/L) and Ang II (≥10-6 mol/L) caused a significant degradation of F-actin (less assembly F-actin fibers and more disassembly fibers). ERK1/2 inhibitor U0126 (10 µmol/L) and NF-κB inhibitor JSH-23 (10 µmol/L) both markedly suppressed glucose- and angiotensin II-induced fibronectin and collagen expressions in cardiac fibroblasts. Furthermore, pretreatment with liraglutide (10-100 nmol/L) or linagliptin (3 and 30 nmol/L) significantly decreased glucose- and Ang II-induced expression of fibrotic signals, phospho-ERK1/2 and phospho-NF-κB-p65 in cardiac fibroblasts. Moreover, pretreatment with liraglutide (30 nmol/L) or liraglutide (100 nmol/L) markedly inhibited glucose-induced F-actin degradation, however, only liraglutide inhibited Ang II-induced F-actin degradation. CONCLUSION: Linagliptin and liraglutide inhibit glucose- and Ang II-induced collagen formation in cardiac fibroblasts via activation of the ERK/NF-κB/pathway. Linagliptin and liraglutide also markedly inhibit glucose-induced F-actin degradation in cardiac fibroblasts, but only liraglutide inhibits Ang II-induced F-actin degradation.

Atorvastatin prevents development of kindling by modulating hippocampal levels of dopamine, glutamate, and GABA in mice.

PURPOSE: Atorvastatin (ATV) is widely used for the treatment of dyslipidemias. Recent evidence has shown that ATV has protection effects against seizures. However, the effect of ATV on certain neurotransmitter and oxidative stress markers associated with seizures had not been reported. Therefore, the present study aimed to evaluate the effects of ATV on oxidative stress markers on whole brain and GABA, glutamate, and dopamine levels in the hippocampus of PTZ-kindled mice. Additionally, effects of ATV on animal models of seizures, anxiety, and depression were also assessed. MATERIALS AND METHODS: Swiss albino mice were given ATV (20, 40, and 80mg/kg/p.o.) in an acute study. On the seventh day, animals were subjected to various neurological and neurobehavioral tests, viz, increasing current electroshock (ICES) test, pentylenetetrazole (PTZ)-induced seizures, Elevated Plus Maze (EPM), and Forced Swim Test (FST). For the development of kindling, a subconvulsant dose of PTZ, i.e., 25mg/kg, i.p., was administered every other day, and ATV in all the three doses was administered daily. Seizure score was continuously monitored until the development of kindling. Thiobarbituric acid reacting species (TBARS), glutathione, dopamine, GABA, and glutamate levels were also assessed in the brain tissues of mice. RESULTS: The results showed that in the ICES test, ATV 80mg/kg increased the seizure threshold to hind limb extension (HLE), and a complete protection against HLE was observed when ATV 80mg/kg was combined with a subanticonvulsant dose of phenytoin. Atorvastatin in all the tested doses suppressed the development of kindling, reduced lipid peroxidation, and increased glutathione levels. All doses of ATV maintained the normal levels of glutamate, GABA, and dopamine in kindled mice. CONCLUSION: Atorvastatin possesses anticonvulsant activity against electroconvulsions. It was found to suppress the development of PTZ kindling, presumably altering the redox status and hippocampal levels of dopamine, glutamate, and GABA.

Prevalence of depression in patients with type 2 diabetes attending an outpatient clinic in India.

BACKGROUND: Clinical studies have suggested that depression is common among patients with type 2 diabetes (T2D). Depression is an important factor which affects the management and complications of diabetes. However, the available data regarding its prevalence in India are limited. OBJECTIVES: To estimate the prevalence of depression in patients in India with T2D and to compare it with a non-diabetic group; and to determine the association of depression with glycaemic control and complications of diabetes in patients with T2D. METHODS: This case-control study was carried out over 5 months from May to September 2012 at a tertiary care hospital in India. Cases were patients with T2D and controls were individuals without diabetes. Depression was assessed using the Patient Health Questionnaire (PHQ)-9. The sociodemographic profile, duration of diabetes, presence of complications and other medical variables were also analysed. RESULTS: 260 subjects of Indian origin (162 men and 98 women; 130 with known T2D and 130 controls without T2D) were evaluated. The prevalence of depression in subjects with T2D was almost twice that in control subjects (46/130 (35.38%) vs 26/130 (20%); p=0.006). A statistically significant difference was found in the fasting blood glucose levels of subjects with depression and those without depression among the patients with T2D (145.70±53.92 vs 130.61±42.39; p=0.022), but depression was not found to be associated with any of the diabetic complications and glycaemic control. CONCLUSIONS: Our findings demonstrate that there is a higher prevalence of depression in Indian patients with T2D, which is almost twice that in those without T2D. Since patients with T2D are at higher risk of developing depression, assessment of depression should be performed as part of the routine practice in India. TRIAL REGISTRATION NUMBER: CTRI/2012/06/002747.

A systematic review and meta-analysis on efficacy and safety of Ganaxolone in epilepsy.

INTRODUCTION: Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy. METHODS: A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone. RESULTS: The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo. CONCLUSION: Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile. PROSPERO REGISTRATION NUMBER: CRD42023434883.

Comparison of the safety and efficacy of Mitomycin C 0.02% used intra-operatively by subconjunctival injection versus direct scleral application using sponges in phacotrabeculectomy: A prospective randomized controlled trial.

PURPOSE: To compare the safety and efficacy of subconjunctival injection (MMC: 0.02%) to those with subconjunctival application of sponges soaked in Mitomycin C (MMC: 0.02%) intra-operatively in patients who underwent phacotrabeculectomy. METHODS: A total of 68 patients undergoing phacotrabeculectomy were randomized into two groups; the sponge group received 0.02% MMC-soaked sponges (n = 38), and the injection group received subconjunctival injection of 0.02% MMC (n = 30). The primary outcome was post-operative mean intra-ocular pressure reduction (IOP). The secondary outcomes were bleb morphology using Indiana Bleb Appearance Grading Score (IBAGS) and anterior segment optical coherence tomography (AS-OCT), post-operative use of 5-fluorouracil, and complications rates. These were compared at 1 week and 1, 3, and 6 months post-operatively. Complete success was defined as ≥30% reduction in IOP without anti-glaucoma medications. RESULTS: In sponge and injection groups, the mean pre-operative IOP was 29.1 ± 8.1 and 29.8 ± 8.8 mmHg, respectively. At 6 months, IOP in sponge and injection groups reduced by 52% (14 ± 3.6 mmHg, P < 0.001) and 50% (15.2 ± 4.1 mmHg, P < 0.001), respectively. Complete success was observed in 90.9% in the sponge group and 95.83% in the injection group. Both groups had diffuse, shallow, relatively avascular blebs at 6 months using IBAGS and AS-OCT. A few complications were seen in the sponge group during this period, which were not vision-threatening. CONCLUSION: Subconjunctival MMC injection is an effective, safe, convenient, and time-saving alternative to sponge-soaked delivery of MMC in phacotrabeculectomy.

Observation and Assessment of the Parameters of Facial Esthetics in 6-year-old Children with Healthy Dentition.

Aim: This study was conducted to observe and assess the dental and facial parameters of esthetics in children with healthy dentition and evaluate whether they are comparable to those of adults. Materials and methods: An observational study included 70 children with ages ranging from 5 to 6 years who had come to the Department of Pediatric & Preventive Dentistry, Institute of Dental Studies & Technologies, Ghaziabad, Uttar Pradesh, India, with intact primary dentition. Standardized photographs of the children were taken and evaluated. Their facial and dental parameters were recorded and compared to that of those of adults. Result: The relation of tooth and facial components was established, and it was found that they were not in the same proportion as those of adults. Conclusion: The proportions of facial and dental parameters of esthetics of children at 6 years of age are different from those of adults. Clinical significance: Since esthetic rehabilitation of primary teeth is becoming an important requisite of successful dental treatment, it is important to establish a standard guideline of dental and facial parameters for children for prosthetic rehabilitation. How to cite this article: Potsangbam D, Agarwal N, Jabin Z, et al. Observation and Assessment of the Parameters of Facial Esthetics in 6-year-old Children with Healthy Dentition. Int J Clin Pediatr Dent 2023;16(4):608-611.

Comparative evaluation of antimicrobial efficacy of nanosilver solution, Azadirachta indica, sodium hypochlorite, and normal saline as root canal irrigants in primary teeth.

Background: Microorganisms are the main cause of pulpal and periapical diseases. Hence, the elimination of such potential microbes is achieved by endodontic treatment. Mechanical preparation is the main mechanism to reduce the bacterial load in canals which is enhanced by intracanal irrigants. Despite these procedures, some bacteria might persist within the canals. It is important to disinfect the pulp space and dentinal tubules thoroughly with an effective endodontic irrigant to prevent reinfection of a treated root canal. Aim: This study aimed to evaluate and compare the antimicrobial efficacy of nanosilver (NS) Solution, Azadirachta indica, sodium hypochlorite, and normal saline when used as irrigants in infected root canals of primary teeth. Settings and Design: The study was a prospective randomized control trial which was conducted as per the consort statement. Materials and Methods: Eighty pulpally involved primary teeth requiring endodontic treatment of children aged 5-12 years were selected for this study. The subjects were randomly allocated to 4 groups (3 irrigant and control groups) consisting of 20 children each where Group I = NS solution, Group II = A. indica, Group III = Sodium hypochlorite (2.5%), and Group IV = Control group. Microbiological samples were collected at the baseline (before irrigation) and postirrigation after biomechanical preparation using the selected irrigant. The samples were subjected to an anaerobic bacterial culture test. Microbial colonies were identified and expressed as colony forming units per milliliter. Statistical Analysis: Data were analyzed using one-way analysis of variance, Paired t-test, and Post hoc Bonferroni test. Results: NS solution showed the highest mean of 4.384 × 103 ± 1.019 followed by Sodium hypochlorite with a mean of 3.500 × 103 ± 1.193 and A. indica of 2.590 × 103 ± 0.778. Conclusion: Based on the results of this study, NS solution can be used as an alternative to other root canal irrigating solutions in primary teeth.

Longitudinal efficacy of Ertugliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

INTRODUCTION: Ertugliflozin, a sodium-glucose cotransporter-2 inhibitor, seems to improve glycemic control in type 2 diabetes mellitus (T2DM). We aim to evaluate the efficacy of Ertugliflozin across multiple time intervals (18, 26, and 52 weeks) in T2DM patients. METHODS: A literature search was conducted on electronic databases. Data was extracted from eligible studies at both 5 mg and 15 mg doses in monotherapy and as add-on therapy. Cochrane RevMan was used to perform the meta-analysis. RESULTS: Ertugliflozin, at both 5 mg and 15 mg doses, demonstrated a significant improvement in HbA1c levels at 18 weeks 5 mg [P = 0.00001], 15 mg [P = 0.05], and at 26 weeks in monotherapy 5 mg [P = 0.006], monotherapy 15 mg [P = 0.006], 5 mg as add-on therapy [P = 0.00001], 15 mg add-on therapy [P = 0.00001] respectively. At 52 weeks, the reduction in HbA1c was significant in 15 mg add-on therapy [P = 0.0001]. Additionally, ertugliflozin as an add-on therapy also led to a significant reduction in FPG, body weight, and systolic blood pressure. CONCLUSION: Ertugliflozin showed clinical efficacy in improving glycemic control, fasting plasma glucose, body weight, and systolic blood pressure in T2DM patients over the studied time intervals compared to placebo.