Connecting the Dots: Hydration, Micronutrients, and Immunity.

Dehydration, often unnoticed, can occur in adults due to heat-related illnesses, viral infections, and upper respiratory tract infections, leading to deficits in fluids, electrolytes, and energy (FEE), even without diarrhea. This fluid deficit, in turn, impairs immunity at cellular and molecular levels. Physiologically, the immune system rapidly reacts to threats by adjusting its structural permeability, allowing water and small solutes to be passed, facilitated by proteins like aquaporins (AQPs). These AQPs are also essential for immune cell communication and adjustments of the cytoskeleton for functions like chemotaxis and phagocytosis. Apart from hydration, maintaining an optimal intake of essential micronutrients, including vitamins C and E, copper, zinc, and selenium, is also critical for supporting immune function and acting as antioxidants. Transient alterations in immune function caused by acute stressors or nondiarrheal conditions heighten vulnerability to coexisting illnesses, particularly cold and upper respiratory tract infections, while also elevating the likelihood of recurrent health issues. Supplementing fluids with known FEE content according to quality standards and enhanced taste is recommended during acute illness and until complete recovery. Thus, dehydration, caused by various acute conditions, can impair immunity and delay recovery. Prioritizing hydration and nutrition in healthcare and general settings is imperative, even when diarrhea is absent.

Association of Physicians of India Expert Recommendations on Oral Fluid, Electrolytes, and Energy Management during Transition Care and Discharge for Hospitalized Patients with Nondiarrheal Illnesses.

Acute nondiarrheal illnesses (NDIs) involve overt or subclinical dehydration, requiring rehydration and electrolyte repletion. Dehydration is frequently under-recognized and under-managed, both in outpatient departments (OPDs) and inpatient departments (IPDs). Postadmission dehydration is associated with longer hospital stays and higher inhospital mortality rates. Recognizing and understanding dehydration in hospitalized patients is necessary due to the adverse outcomes associated with this condition. In this article, we aimed to develop practical consensus recommendations on the role of oral fluid, electrolyte, and energy (FEE) management in hospitalized patients with FEE deficits in NDI. The modified Delphi consensus methodology was utilized to reach a consensus. A scientific committee comprising eight experts from India formed the panel. Relevant clinical questions within three major domains were formulated for presentation and discussion: (1) burden and factors contributing to dehydration in hospitalized patients; (2) assessment of fluid and electrolyte losses and increased energy requirements in hospitalized patients; and (3) management of FEE deficits in hospitalized patients [at admission, during intravenous (IV) therapy, IV to oral de-escalation, and discharge]. The consensus level was classified into agreement (mean score ≥4), no consensus (mean score <4), and exclusion (mean score <4 after the third round of discussion). The questions that lacked agreement were discussed during the virtual meeting. The experts agreed that the most common factors contributing to dehydration in patients with NDI hospitalized in IPDs include decreased oral fluid intake, increased fluid loss due to the illness, insensible fluid loss, and a lack of awareness among doctors about dehydration, which can result in poor fluid intake. Time constraints, discontinuity of care, lack of awareness of the principles of fluid balance, lack of formal procedures for enforcing hydration schemes, and lack of adequate training are most often barriers to the assessment of hydration status in hospital settings. Experts used hydration biomarkers, such as changes in body weight, serum, or plasma osmolality; fluid intake; and fluid balance charts; along with urine output, frequency, quantity, and color, to determine hydration status in hospital settings. Experts agreed that appropriate FEE supplementation in the form of ready-to-drink (RTD) fluids can restore FEE deficits and shorten the length of hospital stays in hospitalized patients at admission, during de-escalation from IV to oral therapy, and at discharge. RTD electrolyte solutions with known concentrations of electrolytes and energy are good choices to avoid taste fatigue and replenish FEE in hospitalized patients during transition care and at discharge.

Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.

Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.

Comprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing Factor U2AF1 in Leukemia Cells.

Mutations in RNA splicing factor genes including SF3B1, U2AF1, SRSF2, and ZRSR2 have been reported to contribute to development of myeloid neoplasms including myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML). Chemical tools targeting cells carrying these mutant genes remain limited and underdeveloped. Among the four proteins, mutant U2AF1 (U2AF1mut) acquires an altered 3' splice site selection preference and co-operates with the wild-type U2AF1 (U2AF1wt) to change various gene isoform patterns to support MDS cells survival and proliferation. U2AF1 mutations in MDS cells are always heterozygous and the cell viability is reduced when exposed to additional insult affecting U2AF1wt function. To investigate if the pharmacological inhibition of U2AF1wt function can provoke drug-induced vulnerability of cells harboring U2AF1 mut , we conducted a fragment-based library screening campaign to discover compounds targeting the U2AF homology domain (UHM) in U2AF1 that is required for the formation of the U2AF1/U2AF2 complex to define the 3' splice site. The most promising hit (SF1-8) selectively inhibited growth of leukemia cell lines overexpressingU2AF1 mut and human primary MDS cells carrying U2AF1 mut . RNA-seq analysis of K562-U2AF1mut following treatment with SF1-8 further revealed alteration of isoform patterns for a set of proteins that impair or rescue pathways associated with endocytosis, intracellular vesicle transport, and secretion. Our data suggested that further optimization of SF1-8 is warranted to obtain chemical probes that can be used to evaluate the therapeutic concept of inducing lethality to U2AF1 mut cells by inhibiting the U2AF1wt protein.

Strategies to Improve Colonoscopy Preparation in Inflammatory Bowel Disease. A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND AND AIMS: Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and surveillance for neoplasia. We performed a systematic review of randomised trials of various bowel preparations for colonoscopy in IBD. METHODS: We searched various electronic databases (PubMed, Embase, and CENTRAL) for studies reporting about the use of various strategies to improve colonoscopy preparation in IBD. We included only randomized clinical trials (RCTs). A network meta-analysis was done using a frequentist approach to compare the effectiveness of various bowel preparations. The risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcome parameters like compliance, tolerance, acceptance, and adverse effects were assessed qualitatively. RESULTS: Seven RCTs reporting about 960 patients were included. On comparison with 4 liter (L) of poliethylen glycol (PEG), oral sulfate solution (OR=1.1, 95%CI: 0.65-1.86); PEG2L/Ascorbate (OR=0.98, 95%CI: 0.65-1.48); PEG1L (OR=1, 95%CI: 0.55-1.81); PEG2L plus bisacodyl (OR=1.08, 95%CI: 0.71-1.65); PEG4L plus simethicone (OR=1, 95%CI: 0.67-1.50); PEG/ sodium picosulfate and magnesium citrate (SPMC) 1.5L (OR=0.99, 95%CI: 0.55-1.78); SPMC 2L (OR=1.09, 95%CI: 0.61-1.97) had similar effectiveness. Three RCTs reported compliance, five RCTs reported tolerance, two studies reported patient acceptance and five RCTs reported data on the willingness of patients to repeat the procedure in the future. Low-volume preparations had better compliance, tolerance, acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcomes after colonoscopy like cecal intubation rate, and change in electrolyte levels were found. CONCLUSION: Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.

Assessment of Hydration Status Using Conventional Method and Salivary Osmolarity as a Point-of-care Tool.

Dehydration is a well-known problem worldwide, and its assessment can be challenging due to confusing physical signs. The most effective way to assess hydration status is through the costly stable isotope methodology, but this approach has practical limitations. More commonly accepted and utilized indicators of hydration status are hematological and urinary parameters. However, hematological markers require invasive methods, and urinary markers have varying degrees of success in tracking hydration changes. While alterations in body weight can serve as a means of promptly evaluating hydration status, various factors such as food consumption, fluid intake, fecal losses, and urine production can impact these changes. Researchers have turned their attention to saliva as a potential marker and point-of-care (POC) testing to address the limitations of existing biomarkers. Saliva is appealing due to its easy collection process and similarities to extracellular fluid in terms of water and ion concentrations. Recent studies have shown that saliva flow rate, osmolarity/osmolality, and total protein concentration can effectively monitor changes in body mass during acute dehydration. Misdiagnosing dehydration can have severe clinical consequences, leading to morbidity and even mortality. This narrative review focuses on recognizing the significance of hydration assessment, monitoring, and the potential of salivary osmolarity (SOSM) as an assessment tool. Healthcare professionals can improve their practices and interventions to optimize hydration and promote overall wellness using such tools.

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.

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.

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.

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.

Remineralizing potential of Calcium Sucrose Phosphate in white spot lesions: A Systematic Review.

BACKGROUND: This systematic review aimedto 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 todate. 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 wereselected. 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 favorableoutcomes 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.

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.