Presence of single nucleotide polymorphisms in transforming growth factor ß and insulin-like growth factor 1 in class II malocclusions due to retrognathic mandible.

AIM: The aim of this study was to evaluate specific single nucleotide polymorphisms (SNP) of transforming growth factor-beta (TGF-ß) (rs1800469) and insulin-like growth factor-1 (IGF-1) (rs17032362) genes in Class II individuals with a normal maxilla and retrognathic (short) mandible.

Comparative Evaluation of the Effect of Photobiomodulation on Pain Reduction in Individuals Undergoing Segmental Retraction Using a Closing Loop: A Randomized Controlled Clinical Trial.

BACKGROUND: Pain following orthodontic treatment is a common reason for apprehension and treatment discontinuation. Research on modalities to control pain in orthodontic patients has gained special attention. Low-level laser therapy (LLLT) is studied as an alternative pain management modality free of the adverse effects of analgesic medications. OBJECTIVES: This study evaluated the effectiveness of photobiomodulation therapy (PBMT) for pain control following the activation of a closing loop for canine retraction. METHOD: This is a split-mouth, placebo-controlled, single-blinded randomized clinical trial that evaluated 16 patients who need canine retraction using closing loops. Two maxillary quadrants were allotted into test and control groups using the coin toss method. In the test group, a low-intensity laser with 810 nm wavelength for 60 seconds in pulsated non-contact mode was used in the buccal, palatal, mesial, and distal regions of the canine immediately after activating the loop. The control site received placebo radiation. The pain level was recorded 2, 24, 48, and 72 hours after intervention in the control and test groups using the Visual Analogue Scale (VAS). The test and control groups were compared using Student's t-test. A p-value ≤0.05 was considered statistically significant. Analyses were conducted using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, New York, United States). RESULT: Both groups had a significant statistical difference in the pain score. The laser group showed a statistically significant lower pain score compared to the control group at all time points. CONCLUSION: Photobiomodulation by 810 nm 300 mW diode laser can effectively reduce pain following the retraction of maxillary canines.

Comparative evaluation of clinical success of Stainless Steel and Bioflx crowns in primary molar - A 12 month split mouth prospective randomized clinical trial.

PURPOSE: The purpose of this clinical trial was to assess and compare the clinical outcomes of Bioflx crowns (BFCs) with stainless steel crowns (SSCs) in primary molars (PMs). MATERIALS AND METHODS: This prospective split-mouth randomized controlled clinical trial was conducted between March 2022 and June 2023. Thirty-eight patients (17 females and 21 males) with a mean age of 5.21 years participated in this study. Each child (n = 38) received both SSC and BFC. Clinical and radiographic follow-up was performed at baseline, 3, 6, and 12 months using the modified United States Public Health System scoring criteria to evaluate various parameters. RESULTS: At the 3 and 6 months' follow-up, no significant difference was observed between the two groups. However, at 1-year follow-up, a statistically significant difference (P < 0.05) was evident in the frequency between the two groups for the criteria of crown retention after cementation and anatomic form of the crown, indicating a preference for SSC over prototype 1 BFC. CONCLUSION: The 12-month results indicate that BFC performed similarly to the established SSC for the restoration of PMs providing better esthetics.

Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

Next-Generation Sequencing (NGS): Platforms and Applications.

The demand for accurate, faster, and inexpensive sequencing of deoxyribonucleic acid (DNA) is increasing and is driving the emergence of next-generation sequencing (NGS) technologies. NGS can provide useful insights to help researchers and clinicians to develop the right treatment options. NGS has wide applications in novel fields in biology and medicine. These technologies are of great aid to decode mysteries of life, to improve the quality of crops to detect the pathogens, and also useful in improving life qualities. Thousands to millions of molecules can be sequenced simultaneously in parallel using various NGS methods. NGS can identify and characterize the microbial species more comprehensively than culture-based methods. Recently, the NGS approach has been used for oral microbial analysis.

REMINERALIZING POTENTIAL OF CALCIUM SUCROSE PHOSPHATE IN WHITE SPOT LESIONS: A SYSTEMATIC REVIEW.

BACKGROUND: This systematic review aimed to evaluate the remineralizing efficacy of calcium sucrose phosphate (CaSP) for the treatment of white spot lesions (WSLs) that commonly occur after orthodontic treatment with fixed appliances using various randomized controlled trials (RCTs) available in the literature to date. HIGHLIGHTS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, RCTs that assessed the efficacious remineralizing potential of CaSP on WSLs and demineralized enamel and compared it with either no intervention or other remineralizing agents were selected. The methodological rigor of the included studies was subjected to the Risk of Bias tool-2 (ROB-2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools. Furthermore, a Begg's Funnel Plot was used to assess publication bias. The qualitative analysis encompassed a corpus of 36 studies. The remineralization potential of CaSP was investigated using an array of parameters, including surface microhardness, surface morphology, surface roughness, mineral content, and lesion size and depth. Based on the ROB-2 tool, most of the included studies were judged to be high risk, largely attributable to the presence of attrition bias. Using the GRADE framework, the certainty of evidence was determined to be moderate. CONCLUSION: This systematic review reveals that CaSP yields favorable outcomes in terms of increased surface microhardness and calcium-phosphate content, reduced demineralized area and surface roughness, and enhanced surface topography.

Use of electrical stimulation for accelerated orthodontics in humans: a systematic review and meta-analysis.

AIM: The main objective of this systematic review is to comprehensively evaluate all the relevant studies to evaluate the effectiveness of electrical stimulation to accelerate orthodontic tooth movement in human patients. METHODS: Using a suitable search strategy, various databases like PubMed, CENTRAL, Scopus and Google Scholar were surveyed for relevant randomized controlled trials (RCTs); after which a hand search of related orthodontic journals was completed. The risk of bias of studies was checked using Cochrane's ROB-2 tool. The quality of evidence of the included studies was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Rate of orthodontic tooth movement was compared and thus efficiency of electrical stimulation to accelerate tooth movement was assessed. Meta-analysis was done on 2 studies out of the 4; rate of orthodontic tooth movement was compared at two time periods after start of treatment (3rd month and 5th month) with standardized mean difference (SMD) as summary estimate, with p < 0.05 denoting statistical significance. Publication bias was checked using a funnel plot. RESULTS: Via exploration of the online databases and hand searching, 1080 studies were found after removing duplicates. After full text assessment, 13 studies in total were selected that used electrical stimulation, out of which 4 studies were included in the qualitative analysis as they met the inclusion criteria. The meta-analysis was done for 3rd month and 5th month with SMD as 0.69(-1.26-0.12) and 1.64(-3.44-0.16), respectively. The strength of evidence in the meta-analysis is moderate. There was no publication bias as shown by funnel plot. DISCUSSION: The studies included showed increased risk of selection and performance bias. Also due to the limited number of studies available, there was difficulty in reaching definitive conclusions. The meta-analysis showed a significant difference among the control and experimental group for the 3rd month. CONCLUSION: Even though a positive correlation is found between electrical stimulation and acceleration of orthodontic tooth movement, it is advised to conduct further studies, particularly with human participants, to establish a more conclusive outcome. REGISTRATION: This review has received no funding. The protocol for the study was registered in the Prospective Registration of Systematic Review (PROSPERO)(CRD42023495077).

Chitosan and neem gum-based polyelectrolyte complex for design of allantoin loaded biocomposite film: In-vitro, ex-vivo, and in-vivo characterization.

Presently, the preference for chitosan (CS) and gum polysaccharides in biomedical applications including drug delivery and wound healing has been extensively documented. Despite this, the demerits of CS and gum polysaccharides such as poor mechanical properties, degradation rate, swelling, etc., limit their applications for designing biocomposite films for drug delivery. Therefore, the anticipated work aims to design a CS and neem gum polysaccharides (NGP) polyelectrolyte complex-based allantoin (AT)-loaded (CS/NGP-AT) biocomposite film for improved wound healing. In brief, CS, NGP, and CS/NGP-AT-based biocomposite films were prepared using the solvent-casting method, and in-vitro, ex-vivo, and in-vivo characterizations were performed to assess the performance of these biocomposite films compared to their counterparts. In this, diffractogram and thermogram analysis assured the conversion of crystalline AT into an amorphous form. The optimized CS/NGP/AT-3 formulation exhibited controlled water absorption, appropriate water uptake capacity, good water retention ability, excellent water vapor transmission rate, controlled degradation rate, enhanced mechanical properties, cell and blood biocompatibility, etc. Furthermore, it offered improved antimicrobial, anti-inflammatory, and antioxidant potential. The optimized film provided a modified release (88.3 ± 0.3 %) of AT from the film for up to 48 h. Wound healing experiments on rats and their histopathology studies confirmed a significantly higher rate of wound recovery within 14 days compared to the control and CS/NGP film, attributable to the combined effects of CS, NGP, and AT. In conclusion, the fabricated CS/NGP-based biocomposite film presents promising prospects as an excellent candidate for wound healing applications.

Efficacy of Teleconsultation-Based Rehabilitation in Children with Landry-Guillain-Barré Syndrome: An Open Label Randomized Controlled Trial (Tele Rehab-LGBS Trial).

OBJECTIVES: To evaluate the feasibility and efficacy of teleconsultation-based rehabilitation in children with Landry-Guillain-Barré syndrome (LGBS), measured with Medical Research Council (MRC) sum score and Hughes score. METHODS: A pragmatic, prospective, parallel open label randomized controlled trial was conducted among a total of 50 children with LGBS. The children were randomized using computer generated block randomization into 2 groups (25 in each group): Standard of care (Group A) and teleconsultation-based rehabilitation (Group B). Primary and secondary outcomes were measured with MRC sum score and Hughes score at 12- and 24-wk follow-up. RESULTS: The mean age was 6.4 ± 3.3 y; 29 (58%) were boys. Baseline MRC sum score (median, IQR), and Hughes score (median, IQR) in group A was 24 (7-31) and 5 (4-5) respectively; and in group B was 18 (9-24) and 4 (4-5) respectively. At discharge, median (IQR) MRC sum score in group A and B was 34 (28-41), and 30 (25-43) (p value = 0.31) respectively. Tele-rehabilitation was provided to group B for 24 wk with 96% compliance. At 12 wk, median MRC sum score in group A and group B were similar [48 (IQR 44-54) vs. 52 (IQR 46-60), p value = 0.08]. At 12 wk and 24 wk, median Hughes score in group A and B were similar. At 24 wk, 15 out of 23 subjects of group A and 18 out of 25 subjects of group B were ambulatory (p value = 0.61). CONCLUSIONS: Teleconsultation-based rehabilitation was feasible with a high compliance rate. The functional outcomes measured with MRC sum score and Hughes score were similar in both the groups at 12 and 24 wk follow-up. Teleconsultation-based rehabilitation has similar efficacy as physical rehabilitation.

Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats.

OBJECTIVES: Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI's presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats. METHODS: Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5 mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24 h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment. RESULTS: ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14 µg h/mL) and DARP (16.15±4.50 vs. 8.75±2.79 µg h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations. CONCLUSIONS: RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.

Naturalistic Evaluation of ERAS Bundle Implementation Feasibility in Elective Cesarean Deliveries of Tertiary Care Hospital in a Low-Middle-Income Country.

The present study assessed whether applying enhanced recovery after surgery (ERAS) guidelines for cesarean delivery is feasible in the tertiary care setting with an add-on objective to identify barriers to successful implementation. The cross-sectional study included women undergoing elective CS and willing to participate. The study attempted to understand barriers to ERAS implementation through timely interviewing study participants. Sixty-two patients participated in the study. Antenatal and fetal complications were observed in 39(63%) and 32(51%) participants. The study observed that at least 80% of the proposed components could be applied to 71% of the study population. All 15 components could be applied to 7(11.2%) patients, and at least 50% could be applied to 58(94%) patients. The least applied component was minimizing starvation by taking clear liquids until 2 hrs before surgery in 26(42%) patients due to waiting hours outside the operation-theater (OT). When fitness-for-discharge was assessed against the percent components of ERAS implemented, the area under the curve (AUC) value was 0.75, with a specificity value of 95.65% and a positive predictive value of 94.12%. In the postoperative ERAS bundle, fitness-for-discharge on day-two was statistically associated with early and frequent breastfeeding (p = 0.000) and prevention of intra-op hypotension (p = 0.03). In conclusion, the primary barriers to implementing ERAS were resource limitations in the form of single functional OT and limited doctors.

Effect of Postmeal Fast-Acting Insulin Aspart Injection on the Frequency of Hypoglycemia among Pre-School Children with Type 1 Diabetes: An Open-Label, Cross-Over, Randomized Control Trial.

OBJECTIVES: To study the effect of postmeal Fast-acting insulin Aspart (Fiasp®) on the frequency of hypoglycemia compared to premeal injection among preschool children with type 1 diabetes. METHODS: A single-center trial was conducted among 65 pre-school children (6 mo to 6 y) with Type 1 diabetes for at least 6 mo, on multiple daily insulin injections. Children were randomized to receive their meal bolus postmeal or premeal for the first 3 mo, followed by cross-over at 3 mo. The two groups were compared at the end of 6 mo for the change in frequency of hypoglycemia and hyperglycemia, HbA1c, glycemic variability, and parental satisfaction. Ten children (5 in each group) underwent pharmacokinetic studies. The trial was approved by Institutional Ethics Committee and registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750. RESULTS: Fifty-four children completed the study, with 27 children in each group. There were no significant differences in the frequency of clinical (p = 0.921), severe (p = 0.167) or serious (p = 0.753) hypoglycemia in the two groups. There were no differences in secondary outcome parameters and pharmacokinetics. CONCLUSIONS: The premeal or postmeal injection of Fiasp® does not affect the frequency of hypoglycemia or other glycemic control parameters among pre-school children with Type 1 diabetes. TRIAL REGISTRATION: The trial is registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750.

Factors contributing to flares of ulcerative colitis in North India- a case-control study.

BACKGROUND: Ulcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized. METHODS: The present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI < 4 and a normal fecal calprotectin. A questionnaire evaluating recent infections, stress, drug intake (antibiotics, pain medication), adherence to therapy, and use of complementary and alternative therapy (CAM) was administered. RESULTS: We included 84 patients (51 with flare and 33 in remission) with a median age of 38 years, of whom 47 (55.9%) were males. The two groups were similar for baseline parameters, including age (38, 23-50 and 38, 25.5-48.5 years), male gender (52.9% and 60.6%), extent of disease, extraintestinal manifestations (21.6% and 12.1%), use of 5-aminosalicylates (76.5% and 90.9%). The thiopurine use was lower in those having a flare (15.7% and 36.4%). Amongst the predictors of flare, the recent infections (39.2% and 30.3%), recent travel (31.4 and 27.3%), eating outside food (47.1% and 39.4%), consumption of milk products (88.2% and 75.8%), use of pain medication (43.1% and 33.3%) and recent stress (62.7% and 60.6%) were similar between cases and controls. The rates of antibiotic use (29.4% and 6.1%), lack of adherence (50.9% and 15.2%), and intake of CAM (70.6% and 33.3%) were higher in those with flare. Patients attributed a lack of adherence to the cost of therapy, presumed cure (due to lack of symptoms), and fear of adverse effects. CONCLUSION: Lack of adherence to inflammatory bowel disease therapies and recent CAM and antibiotic intake was higher in patients with flares of UC. The study makes ground for educational intervention(s) promoting knowledge and adherence to IBD therapies.

Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.

OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.

Pharmacokinetic Assessment of Pyrazinamide and Pyrazinoic Acid in Carbon tetrachloride-induced Liver Injury Model in Wistar Rats.

Background: We investigated the pharmacokinetic behavior of pyrazinamide (PZA) and pyrazinoic acid (PA) in the presence of carbon-tetrachloride (CCl4) plus antitubercular treatment (ATT) drug-induced liver injury (DILI) in rats. Methods: Thirty rats utilized in the experiment were separated equally into five groups. Each rat was injected with 0.5 ml/kg CCl4 intra-peritoneal injection on day zero. Group, I rats did receive only CCl4 (single i.p. injection, 0.5 ml/Kg in olive oil in a 1:1 ratio). Groups II, III, IV, and V did receive daily oral PZA, PZA plus isoniazid (INH), rifampicin (RMP) plus pyrazinamide (PZA), and three drugs together, respectively, for 21-days. Pharmacokinetic sampling was performed at 0, 0.5,1,3,6,12 and 24 hours post-dosing on day-20. Liver function test (LFT) was assessed at days 0,1,7, and 21 days after CCl4 and ATT administration, and rats were sacrificed on the last experiment day. Results: ATT treatment maintained the liver function changes initiated by CCl4 administration. An evidential LFT rise was observed in groups administered with pyrazinamide. Co-administration of Isoniazid caused a 2.02 and 1.78 times increase in Area-under-the-curve (AUC) values of PZA and PA, respectively (p < 0.05). Histological and oxidative-stress changes supported the biochemical and pharmacokinetic observations. Conclusion: The enzyme inhibitory capacity of isoniazid is well-preservd in CCl4-induced liver injury.

Pharmacokinetic Assessment of Isoniazid and Acetylisoniazid in Carbon Tetrachloride-Induced Liver Injury Model in Wistar Rats.

Background: N-acetyl transferase 2 (NAT2) polymorphism testing could not see the light of success as a biomarker tool in tuberculosis management. Additionally, the antitubercular treatment (ATT) drug's reintroduction regimen variations exist because of the scarcity of robust preclinical evidence on ATT drug metabolism. Objective: The experiment was planned to understand the pharmacokinetic (PK) behavior of isoniazid and acetylisoniazid (AcINH) in a Wistar rat model of acute liver injury induced by carbon tetrachloride (CCl4) and preclinical drug-induced liver injury (DILI) model induced with CCl4 + anti-Tuberculosis (TB) drugs together. Materials and Methods: Thirty rats were used for the experiment and were divided into five groups. All rats were administered a single 0.5 ml/kg CCl4 intraperitoneal injection on day 0 to induce an animal model of DILI. Group I rats received CCl4 alone. Groups II-V were started on additional gavage feedings of isoniazid (H) alone, H plus rifampicin (R), H plus pyrazinamide (Z), and H, R, and Z together, respectively, daily for 21 days subsequently. Isoniazid and AcINH PK assessment was accomplished on day 20 of continuous once-daily dosing. Liver function test (LFT) monitoring was done at baseline on days 1, 7, and 21. On the last day of experiments, all experimental rats were sacrificed. Results: Three-week ATT administration sustained the CCl4-induced LFT changes. Area under the curve (AUC) values for isoniazid and AcINH were found to be 2.24 and 1.69 times higher in the H + R group compared with the CCl4 + H group, respectively (P < 0.05). Isoniazid and AcINH maximum concentration (Cmax) reached the highest, while isoniazid clearance reached the lowest in the H + R group. AcINH AUC increased by double in the CCl4 + Isoniazid+Rifampicin+Pyrazinamide (HRZ) group compared with the CCl4 + H group (P < 0.05). Biochemical, histological, and antioxidant changes were consistent with the new liver injury model's development. Conclusion: Rifampicin almost doubles up the isoniazid and AcINH exposure, in presence if DILI.

Comparison of stainless steel and titanium-molybdenum alloy closing loop archwires using numeric simulation model based on finite element method.

INTRODUCTION: The objective of this study was to determine and compare the moment-to-force (Mc/F) ratio and the type of tooth movement generated in the anterior and posterior segments in orthodontic space closure with stainless steel and titanium-molybdenum alloy loop archwires. METHODS: Three-dimensional model of the maxilla from which the first premolar was extracted, 18 × 25-mil slot stainless steel brackets, and 16 × 22-mil stainless steel and ß titanium-molybdenum alloy (TMA) closing loop archwires with anterior gable bend of 15° and posterior gable bend of 25° were constructed. The archwires were engaged in the brackets, and 1-mm activations were carried out, which were repeated 5 times. The anterior and posterior segment Mc/F ratio and the type of tooth movement generated by the 2 wires were compared. RESULTS: It was found that the Mc/F ratio for the anterior segment was approximately 5 mm, and for posterior teeth was approximately 10 mm for both stainless steel and TMA closing loop archwire. The anterior teeth exhibited controlled tipping, whereas the posterior teeth showed bodily tooth movement, which was in accordance with the Mc/F ratio that was obtained. CONCLUSIONS: The Mc/F ratio and the type of tooth movement exhibited by stainless steel and TMA closing loop archwires were similar in both anterior and posterior segments.

Role of Biliary Stent in Recurrence of Biliary Stones and Complications After Stone Clearance in Patients Awaiting Cholecystectomy: A Randomized Trial.

INTRODUCTION: The role of prophylactic biliary stenting after clearance of choledocholithiasis in patients awaiting cholecystectomy for concomitant cholelithiasis is controversial. We planned a randomized controlled trial to study the effect of prophylactic biliary stenting after achieving biliary clearance in reducing recurrence of choledocholithiasis and biliary complications in patients awaiting cholecystectomy. METHODS: Patients with concomitant cholelithiasis and choledocholithiasis were included, and those who had evidence of clearance of choledocholithaisis (documented on occlusion cholangiogram during endoscopic retrograde cholangiography [ERC]) were randomized to prophylactic biliary stenting or no stenting. Choledocholithaisis recurrence rate (primary outcome), biliary complications and need for repeat/emergency ERC (secondary outcomes) were compared till 3 months after clearance. RESULTS: Between September 2021 and July 2022, 70 patients were randomized into group A, stenting (n = 35), and group B, no stenting (n = 35). Sixty-six patients were included in the final analysis. Baseline characteristics were comparable between the 2 groups. Ten (15.2%) patients had recurrence of choledocholithiasis, and it was comparable between the 2 groups (7/34 [20.6%] and 3/34 [9.4%], P = 0.306). Five patients (2 cholecystitis and 3 post-ERC pancreatitis) from the stent group while none from the no stent group developed complications, and this difference was statistically significant ( P = 0.024). None of the patients in both the groups needed emergency ERC during the follow-up. DISCUSSION: This randomized trial shows a higher complication rate with prophylactic stenting, while there is no benefit in preventing choledocholithiasis recurrence in patients waiting for cholecystectomy after biliary clearance (CTRI registration number: CTRI/2021/09/036538).

ipso-Cyclization of unactivated biaryl ynones leading to thio-functionalized spirocyclic enones.

Ceric ammonium nitrate (CAN)-promoted oxidative ipso-cyclization of unactivated biaryl ynones with S-centered radicals (SCN/SCF3) to access spiro[5,5]trienones has been established. This approach displayed excellent regioselectivity towards spirocyclization and tolerated a variety of functional groups. Dearomatization of hitherto unknown aryl/heteroaryl groups is also disclosed. DMSO is employed as a low-toxicity, inexpensive solvent as well as a source of oxygen.

Generic ibrutinib a potential cost-effective strategy for the first-line treatment of chronic lymphocytic leukaemia.

Though the chronic lymphocytic leukaemia (CLL) management options in India are still limited compared to the novel drug options in resource-rich settings, the availability of less costly generics and the government health insurance scheme has enabled many patients to access the newer drugs in India. The current study compared the cost-effectiveness and cost-utility of existing initial management options for the progression-free survival (PFS) time horizon from the patient's perspective. A two-health-state, PFS and progressive disease, Markov model was assumed for three regimens (generics): ibrutinib monotherapy, bendamustine-rituximab (B-R), and rituximab-chlorambucil (RClb) used as the frontline treatment of CLL patients in India. All costs, utilization of services, and consequences data during the PFS period were collected from interviewing patients during follow-up visits. The transition probability (TP) and average PFS information were obtained from landmark published studies. EQ-5D-5L questionnaires were utilized to assess the quality of life (QoL). Quality-adjusted life years (QALY) were measured during the PFS period. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were studied. Upon analysis, the entire monetary expense during the PFS time was ₹1581964 with ibrutinib, ₹171434 with B-R, and ₹91997 with RClb treatment arm. Pooled PFS and QALY gain was 10.33 and 8.28 years for ibrutinib, 4.08 and 3.53 years for the B-R regimen, and 1.33 and 1.23 years in RClb arms, respectively. Ibrutinib's ICER and ICUR were ₹214587.32 per PFS year gain and ₹282384.86 per QALY gain when assessed against the B-R regimen. Ibrutinib also performed better in ICER and ICUR against the RClb arm with ₹157014.29 per PFS year gain and ₹200413.6 per QALY gain. In conclusion, generic ibrutinib is a cost-effective initial line of management compared to other commonly used treatment regimes in resource-limited settings.