Acute Liver Failure With Liver Enzymes >5,000 in Sickle Cell Disease.

Sickle cell disease is a hemoglobinopathy often complicated by painful vaso-occlusive episodes, acute chest syndrome, stroke, and myocardial infarction. Sickle cell intrahepatic cholestasis (SCIC) is a rare and potentially fatal complication of sickle cell disease. SCIC is thought to involve progressive hepatic injury due to sickling within sinusoids. We present the case of a young patient with SCIC and acute liver failure, requiring prompt treatment with exchange transfusion. Our case describes features that should raise suspicion for hepatic failure in SCIC and highlights exchange transfusion as a successful management approach in similar patients with an otherwise high risk of mortality.

An observational study on the prevalence of choledochal cyst with pancreatitis: Geographical implications and management.

The objective of this study was to analyse the prevalence, risk factors and need for intervention in a sample of Indian children with choledochal cyst (CDC) complicated by pancreatitis with a special focus on chronic pancreatitis. A retrospective review of medical records of children admitted with CDC over 11 years was done and pancreatitis identified using INSPPIRE guidelines. Children were divided into two groups-one having choledochal cyst alone and the other choledochal cyst along with pancreatitis to determine associated risk factors. 40.2% of children with CDC had pancreatitis based on elevation of enzymes or radiological imaging. Age, total bilirubin and indirect bilirubin, requirement of intervention was significantly higher in the group with pancreatitis. 47% of those with radiological features of pancreatitis had imaging features of chronic pancreatitis. Chronic pancreatitis has not been reported previously in children with CDC and maybe peculiar to the Indian subcontinent.

Efficacy of titratable mandibular advancement device versus continuous positive airway pressure therapy in the treatment of obstructive sleep apnea: A clinical crossover trial.

Background: To compare efficacy of continuous positive airway pressure (CPAP) and oral appliance (OA) in management of various grades of obstructive sleep apnea (OSA). Methods: Thirty polysomnography diagnosed cases of OSA were divided into three groups based on baseline apnea hypopnea index (AHI) as follows: group 1: mild OSA (AHI = 5-14.9), group 2: moderate OSA (AHI = 15-29.9), and group 3: severe OSA (AHI >30) with 10 patients in each group. Half of the patients in each group were randomly allocated to CPAP or OA therapy, and crossover of therapy was performed after two months. AHI, Epworth's Sleepiness Scale (ESS), and mean oxygen saturation (SPO2) were measured at baseline, after each arm of treatment and after the crossover. A questionnaire survey including information regarding pretreatment sleep symptoms and improvement after therapy was performed at above time frames. At the end of therapy, the patients were surveyed regarding satisfaction and perceived effectiveness with both modalities. Results: CPAP was more efficacious in reducing AHI and SPO2 as compared with OA across the three study groups. The improvement in most sleep-related symptoms was higher with CPAP. The satisfaction and perception on effectiveness of treatment were higher with OA than CPAP across three study groups (P-value<0.05 for all). Conclusions: OA is an effective alternative to CPAP across all grades of OSA in selected cases, which is more preferred owing to higher effectiveness and satisfaction among the patients.

Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection.

During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects. Interestingly, our data revealed an association between severe coronavirus disease 2019 (COVID-19) and DDP4, namely that DPP4 levels increased in the plasma of patients with COVID-19 and were correlated with age and disease progression. Although we could not determine the direct effect of DDP4 on viral replication, mechanistic studies in cell culture revealed a negative impact on the expression of the tight junction protein zonula occludens-1 (ZO-1), which contributes to epithelial barrier function. Mass spectrometry analysis indicated that DPP4 overexpressing cells exhibited a decrease in ZO-1 and increased expression of pro-inflammatory cytokines and chemokines. By investigating the effect of DPP4 on the barrier function of human primary cells, we detected an increase in ZO-1 using DPP4 inhibitors. These results provide an important contribution to our understanding of DPP4 in the context of senescence, suggesting that DPP4 plays a major role as part of the SASP. Our results provide evidence that cellular senescence, a hallmark of aging, has an important impact on respiratory infections.

Estimation of exocrine pancreatic insufficiency in children with acute pancreatitis using the 13C mixed triglyceride breath test.

BACKGROUND: /Objective: The extent of exocrine pancreatic insufficiency (EPI) in the paediatric population with acute pancreatitis (AP) is unknown. The primary objective was to use a 6 h stable-isotope breath test to determine the prevalence of EPI in children with AP. The secondary objective was to determine the diagnostic ability of a 4 h abbreviated breath test in the detection of EPI. METHODS: 13C-mixed triglyceride (MTG) breath test was used to measure fat digestibility in 12 children with AP and 12 normal children. EPI was diagnosed based on a cumulative dose percentage recovery (cPDR) cut-off value < 26.8% present in literature. To reduce the test burden, the diagnostic accuracy of an abbreviated 4 h test was evaluated, using a cPDR cut-off that was the 2.5th percentile of its distribution in control children. RESULTS: The cPDR of cases was significantly lower than that of controls (27.71 ± 7.88% vs 36.37 ± 4.70%, p = 0.005). The cPDR during acute illness was not significantly different to that at 1 month follow up (24.69 ± 6.83% vs 26.98 ± 11.10%, p = 0.52). The 4 h and 6 h breath test results correlated strongly (r = 0.93, p < 0.001) with each other. The new 4 h test had 87.5% sensitivity and 93.8% specificity for detecting EPI. CONCLUSION: Two-thirds (66.7%) of this sample of children with AP had EPI during admission, which persisted at 1 month follow up. The 4 h abbreviated 13C-MTG breath test has good diagnostic ability to detect EPI in children and may improve its clinical utility in this age group.

A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor.

PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy. RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed. CONCLUSIONS: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.

Developing a module for early clinical exposure: Experience of five years.

BACKGROUND: Preclinical students often fail to appreciate the clinical relevance of basic sciences during the first year of undergraduate medical training, leading them to lose interest in the subject, and preventing them from achieving the desired goals. In order to rectify this gap in the curriculum, Medical Council of India (MCI) in 2011 published a document announcing curricular strategies including Early Clinical Exposure (ECE) to effectively modify the Indian system of education. Lack of proper guidance prevented many institutions from implementing ECE. Since our institution had run a similar program of "Clinical Observership" as early as 2001, we were able to implement ECE in an efficient way. MATERIALS AND METHODS: Early clinical exposure was implemented as a structured program, with the participation of 10 clinical departments since 2013. Feedback from the students, soon after ECE and also from the batch of CRRIs, who had undergone this program while they were preclinical students amply support the effectiveness of ECE in its contents and methods of implementation. Manual content analysis was performed on open comments. After reading the responses, they were broken down to meaning units, and these were then condensed. The condensed meaning units were labeled with codes. The codes were grouped into categories. Themes were derived from the categories. RESULTS: Out of the 70 CRRIs, 52 responded to the questionnaire. All the CRRIs except one said that ECE was very helpful during their clinical postings and internship period. They suggested that the number of hours of posting should be increased and also reiterated the fact that a greater number of clinical departments could be included in the program. Though the beneficial effects were felt in all the domains of learning, the most remarkable impact was felt in the affective domain, wherein changes are not easy to come by. DISCUSSION: Recently, National Medical Council has come out with plans of including ECE in the syllabus with strict time schedule. It is felt that the faculty will find our experience of running the program for the past five years helpful in implementing this program, for the fullest benefit of the preclinical students.

Surgical versus nonsurgical treatment of acute Achilles ruptures in the high demand patient: Using decision analysis to help clinical decisions.

BACKGROUND: Recent literature suggests that functional treatment of acute non-insertional Achilles tendon ruptures yields outcomes (re-rupture and function) similar to those of surgery, but does not address the unique issues in treating high performance athletes or other high demand patients. METHODS: Decision analysis was used to develop an estimate of outcome utility for both types of treatment using published Costs and Quality-Adjusted Life Years (QALYs) values. The expected value for either treatment was then calculated for high, intermediate, and normal demand patients, using the specific functional needs of the patients. RESULTS: Nonoperative treatment is the preferred management for normal demand patients, while high and intermediate demand patients are more likely to experience better expected functional outcomes from surgery. CONCLUSION: The combination of a decision analysis and expected value analysis provides evidence-based support for the existing intuitive recommendations that favor surgical treatment in elite athletes and other high demand patients. LEVEL OF EVIDENCE: III.

A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas.

PURPOSE: This study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of milademetan, a small-molecule murine double minute-2 (MDM2) inhibitor, in patients with advanced cancers. PATIENTS AND METHODS: In this first-in-human phase I study, patients with advanced solid tumors or lymphomas received milademetan orally once daily as extended/continuous (days 1-21 or 1-28 every 28 days) or intermittent (days 1-7, or days 1-3 and 15-17 every 28 days) schedules. The primary objective was to determine the recommended phase II dose and schedule. Secondary objectives included tumor response according to standard evaluation criteria. Predefined analyses by tumor type were performed. Safety and efficacy analyses included all patients who received milademetan. RESULTS: Between July 2013 and August 2018, 107 patients were enrolled and received milademetan. The most common grade 3/4 drug-related adverse events were thrombocytopenia (29.0%), neutropenia (15.0%), and anemia (13.1%). Respective rates at the recommended dose and schedule (260 mg once daily on days 1-3 and 15-17 every 28 days, ie, 3/14 days) were 15.0%, 5.0%, and 0%. Across all cohorts (N = 107), the disease control rate was 45.8% (95% CI, 36.1 to 55.7) and median progression-free survival was 4.0 months (95% CI, 3.4 to 5.7). In the subgroup with dedifferentiated liposarcomas, the disease control rate and median progression-free survival were 58.5% (95% CI, 44.1 to 71.9) and 7.2 months overall (n = 53), and 62.0% (95% CI, 35.4 to 84.8) and 7.4 months with the recommended intermittent schedule (n = 16), respectively. CONCLUSION: An intermittent dosing schedule of 3/14 days of milademetan mitigates dose-limiting hematologic abnormalities while maintaining efficacy. Notable single-agent activity with milademetan in dedifferentiated liposarcomas has prompted a randomized phase III trial (MANTRA).

Expert Consensus Recommendations on Time in Range for Monitoring Glucose Levels in People with Diabetes: An Indian Perspective.

Keeping up with the global scenario, diabetes prevalence is on rise in India. Inadequate glycemic control is a major cause of diabetes-related morbidity and mortality. The conventional standards of care (SOC) in diabetes, including self-monitoring of blood glucose and measurement of glycated hemoglobin, have supported achievement of glycemic control, yet there are a few limitations. With the use of current technologies and metrics, such as continuous glucose monitoring (CGM) and standardized CGM data reporting, the continuous real-time glucose levels can be measured, and importantly, the percentage of time above, below, and within the target glucose range can be calculated, which facilitates patient-centric care, a current goal in diabetes management. International consensus recommendations endorse the incorporation of CGM and CGM data reporting in SOC for diabetes management. The guidelines provide time in range (TIR) thresholds for different patient populations and different types of diabetes. However, extrapolation of these global guidelines does not aptly cover the Indian population, which has diverse diet, culture, and religious practices. In this context, a consensus meeting was held in India in 2021 with experts in the field of diabetes care. The purpose of the meeting was to develop consensus recommendations for TIR thresholds for different patient profiles in India. Those expert recommendations, together with an evidence-based review, are reported here. The aim of this agreement is to aid clinicians across India to routinely use CGM and CGM data reports for optimizing individualized diabetes care, by implementing clinical targets for TIR.

Influence of Serum Levels of Vitamin D on Insulin Resistance in Patients with Type II Diabetes Mellitus.

BACKGROUND: Vitamin D plays an important role in bone and modulates mineral metabolism and immune function with probable link to several chronic and infectious conditions. In vivo studies have revealed that vitamin D deficiency reduces insulin secretion capacity of the islet beta cells in pancreas. Several studies have shown a correlation between vitamin D levels and insulin resistance, nonetheless, extensive studies showing the relationship between the two are lacking especially among southern Indian population. So the present study was aimed at evaluating the relationship between vitamin D and insulin resistance by using homeostatic model assessment-insulin resistance (HOMA-IR). MATERIALS AND METHODS: In a cross-sectional study, 184 people among which 92 were diabetic and 92 were nondiabetic were recruited at RL Jalappa Hospital, Kolar in the Department of Medicine between May 2018 and April 2019. Fasting serum insulin (I0), fasting plasma glucose (G0), hemoglobin A1c (HbA1C), renal function test, liver function test (LFT), lipid profile, and vitamin D levels were estimated. IBM SPSS version 22 was used for statistical analysis. RESULTS: The prevalence of vitamin D deficiency in our study was (72) 78.2% among diabetic cases and (59) 64.1% among the nondiabetic controls, with the diabetic cases showing lower levels of vitamin D than the controls, however, it was not statistically significant. There was no significant difference in homeostatic model assessment-beta-cell function (HOMA-B) and HOMA-IR between vitamin D deficient and nondeficient groups among cases and controls. CONCLUSION: Vitamin D deficiency is prevalent in both type II diabetes mellitus (T2DM) as well as nondiabetic. Furthermore, there is no association between vitamin D deficiency and insulin resistance or beta-cell function.

46 XY disorder of sex development (DSD) due to 5 alpha (SRD5A2) deficiency - Experience from a multidisciplinary Pediatric Gender Clinic.

BACKGROUND: SRD5A2 deficiency leads to incomplete masculinization of individuals with a 46 XY karyotype. A definitive diagnosis in early infancy facilitates decisions concerning choice of sex of rearing and management. AIM: To review the clinical presentation, diagnosis, treatment and outcome of children with 46 XY DSD due to SRD5A2 deficiency at a Paediatric Gender Clinic. STUDY DESIGN AND METHODS: Retrospective review of cases of SRD5A2 deficiency (2000-15) managed with a standard protocol at a multidisciplinary clinic. Demographic data, clinical presentation, physical findings, investigations (hormonal profile, imaging, genitoscopy), psychological evaluation (child, family), medical and surgical management, outcome and follow up were collated and analyzed. RESULTS: There were 12 cases aged 3 days-14 years at presentation, 3 had parental consanguinity. Eight were reared as males and 4 as females. Specialist referral was sought for hypospadias (5), atypical genitalia (5) or incongruent pubertal masculinization (2). All had chordee, symmetrical inguinoscrotal gonads, rugose labioscrotum and proximal hypospadias (perineoscrotal -9, perineal -3). Both pubertal cases had significant masculinization and no gynecomastia. The median testosterone/dihydrotestosterone ratio was 22.1(IQR-8.6-55.7). Despite a classical phenotype, four (2 prepubertal, 2 pubertal) had a ratio <10. Genitoscopy showed urogenital sinus remnant (4) and hypoplastic verumontanum (5). Sex reassignment was done in 4. Surgical management was staged and completed by 4 years in those with infantile presentation. Besides correction of chordee and urethroplasty in 11, other procedures included orchidopexy (5), excision of a urogenital sinus remnant (4) and correction of penoscrotal transposition (4). The urethroplasty was single staged in 3. All operated cases were followed up (mean age at last follow up - 10.63 years, mean follow up period - 7.25 years). The overall cosmetic result was satisfactory, but the phallic structure remained relatively small across prepubertal period. Uroflowmetry curves were normal in 9. All showed penile tumescence/erection and two peripubertal cases had typical secondary sexual characters. All cases, including those with sex reassignment, have a well-adjusted male psyche. DISCUSSION AND CONCLUSION: The diagnosis, management and longitudinal follow up of cases of SRD5A2 deficiency at a multidisciplinary gender clinic is presented. Diagnostic dilemmas with low T/DHT ratios remained in a third of cases. Most were diagnosed in infancy and assigned a male sex of rearing, all underwent staged masculinizing genitoplasty. Those with sex reassignment also fared well with comprehensive management after family counseling.

Hemodynamic changes during exodontia in hypertensive and normotensive patients following injection of local anesthetics with and without epinephrine: a prospective comparative study / Cambios hemodinámicos durante la extracción en pacientes hipertensivos y normotensivos tras la inyección de anestésicos locales con y sin epinefrina: un estudio comparativo prospectivo

Introduction: Hypertensive patients are frequently encountered in routine dental practice and exodontia procedures. Possibility of cardiovascular complications can be anticipated in these patients. This study compares blood pressure, heart rate, and peripheral capillary oxygen saturation, in normotensive and hypertensive patients prior to, during and after dental extractions. Patients and methods: A prospective comparative study was carried out in 100 (N = 100) patients between the age group of 40-70 years. 50 patients diagnosed with Stage I hypertension and 50 patients who were normotensives, requiring extraction of tooth were recruited. They were further divided into four groups namely, A, B, C and D, each consisting of 25 (n = 25). Group A included patients with controlled hypertension who were administered local anesthesia with epinephrine, while Group B had patients with controlled hypertension who were administered local anesthesia without epinephrine. Group C had normotensive patients who were administered local anesthesia with epinephrine and normotensive patients who were administered local anesthesia without epinephrine were under group D. The patients were evaluated at preoperative, intra operatively and post-operative interval for blood pressure, heart rate and peripheral oxygen saturation. (AU)

Introducción: Con frecuencia, en la práctica dental habitual y en los procedimientos de exodoncia se encuentran pacientes hipertensos. En estos pacientes se pueden anticipar posibles complicaciones cardiovasculares. Este estudio compara la presión arterial, la frecuencia cardiaca y la saturación de oxígeno periférico en pacientes normotensos e hipertensos antes, durante y después de las extracciones dentarias. Pacientes y métodos: Se realizó un estudio comparativo prospectivo en 100 pacientes (n = 100) entre un grupo de edad de 40-70 años. Se reclutaron 50 pacientes con diagnóstico de hipertensión en estadio I y 50 pacientes normotensos que requirieron extracción dentaria. Se dividieron además en cuatro grupos, A, B, C y D, cada uno de los cuales constaba de 25 (n = 25). El grupo A incluyó pacientes con hipertensión controlada a los que se les administró anestesia local con epinefrina, mientras que el grupo B tenía pacientes con hipertensión controlada a los que se les administró anestesia local sin epinefrina. El grupo C tenía pacientes normotensos a los que se les administró anestesia local con epinefrina y los pacientes normotensos a los que se les administró anestesia local sin epinefrina estaban en el grupo D. En el intervalo preoperatorio, intraoperatorio y postoperatorio se evaluaron la presión arterial, frecuencia cardiaca y saturación de oxígeno periférico de los pacientes. (AU)

A comprehensive insight on the biological potential of embelin and its derivatives.

Naturally occurring bioactive molecules are known for their diverse biological applications such as antimicrobial, anticancer, anti-inflammatory, and analgesic activities. Also, some of the natural products act as medicinal drugs. Further, bioactive cell-permeable molecule embelin has been reported for its diverse biological activities such as antimalarial, anticancer, and anti-inflammatory in the literature. With the continuation of our research work on biologically active molecules, based on structural activity relationship and docking studies of embelin and its derivatives, we have reported target-specific anticancer and antimalarial activities of embelin and its analogs. Also, it has been reported in many recent research articles that embelin and its derivatives are known to possess medicinal properties. This review mainly highlights recent reports on broad-spectrum biological activities of the embelin and its analogs to date.

Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals.

The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses.

Evaluation and quantification of airway changes in Class II division 1 patients undergoing myofunctional therapy using twin block appliance.

BACKGROUND: The purpose of the present study was to determine the airway changes in skeletal class II division 1 malocclusion patients with mandibular retrognathism, treated with Twin-Block (TB) appliance. METHODS: Airway assessment was carried for twelve patients (mean age 11.7 ± 1.1 years) who underwent myofunctional therapy using TB appliance for correction of skeletal class II division 1 malocclusion with mandibular retrognathism. Acoustic pharyngometry (AP) was used to assess and quantify the comparative changes in the upper airway, pretreatment and posttreatment. RESULTS: Data acquired was subjected to appropriate statistical analysis. The paired 't' test was used to compare pre-treatment (T0) and after the positive pterygoid response (T1). TB appliance increased mean minimum airway area by 0.28 ± 0.25 cm2 and mean airway by 0.47 ± 0.44 cm2 with 95% CI. Posttreatment minimum airway and mean area changes were found to be statistically significant (P-value<0.01). CONCLUSION: TB appliance therapy has a positive effect on upper airway and is beneficial for the treatment of sleep-related disorders associated with Class II division 1 malocclusion for achieving positive functional changes, esthetics, and healthier quality of life.

Novel Management of Hypersensitive Dentin Using Propolis-based Herbal Desensitizing Agents: An In Vitro Scanning Electron Microscopic Study.

AIM: The objective of this in vitro study was to assess the efficacy of novel propolis-based varnish against the two conventional varnishes on quantitative and qualitative assessments of occlusion of dentin tubules and resistance to erosive and abrasive wears employing scanning electron microscope (SEM). METHODS: Thirty human premolars free from caries extracted due to orthodontic reasons were included in the study. Experimental group was done based on treatment received and divided into three groups. Group A: ClinProXT Varnish (n = 10), Group B: MI Varnish (n = 10), and Group C: Propolis Varnish (n = 10) were applied. Teeth were cleaned and decoronation of crown was done with dentin disks. Dentin specimens of dimension 4 × 4 × 2 mm were prepared and subjected to finishing and polishing. The sample specimens were submersed in EDTA solution for a period of five minutes to open up the dentinal tubules. This was followed by treatment with varnishes and subjection to acidic-abrasive challenge. The specimens were analyzed with an image analyzer connected to SEM for the verification of the number of opened dentin tubules. The parameter assessed in SEM includes size, topography and surface characteristics of dentinal tubule were assessed. The obliteration potential of dentinal tubules was assessed with SEM images. Additionally, the dentin surface loss and resistance to acidic and abrasive wear were also evaluated with SEM. Data were analyzed with two-way analysis of variance (ANOVA) with post hoc Tukey's test. RESULTS: MI Varnish caused higher obliteration of dentin tubules followed by ClinproXT Varnish. Propolis Varnish showed the least obliteration of dentinal tubules among tested experimental groups. After acidic-abrasive challenge, Propolis Varnish was found to be more efficient with less material loss among the experimental groups tested. There was an insignificant difference among the MI Varnish and ClinProXT Varnish groups. CONCLUSION: Simulation of hypersensitive lesions mimicking the clinical scenario was a challenging task in this in vitro study. All varnishes tested in the study had good efficacy in the management of dentin hypersensitivity (DH). Propolis-based varnish had good resistance to material loss after subjection to acidic-abrasive challenge among the tested materials. The casein phosphopeptide (CPP)-amorphous calcium phosphate (ACP)-based MI Varnish had good efficacy to obliterate the dentinal tubules among the tested materials. It was prudent to select the varnishes with good long-term efficacy to survive in the clinical scenario which still remains a challenging task for the clinicians. CLINICAL SIGNIFICANCE: The stability of the varnish plays a vital role in maintenance of its long-term efficacy. The chemical nature along with the ability of the material to interact with the substrate plays a major role in management of DH.

Pharmacognosy, phytochemistry, and molecular studies of an important medicinal herb Achillea millefolium L.

Background: Achillea millefolium L. is traditionally important medicinal herb used for the treatment of various ailments from the centuries. Recent studies showed its biological activities on hay fever, hepato-biliary disorders, and as appetite enhancing drug. It is also reported to be used for the treatments of skin inflammations, wounds, cuts, and abrasions. Aim: To investigate preliminary pharmacognostical, phytochemical, and molecular parameters of aerial parts of the drug. Materials and methods: A. millefolium was identified and collected from the Himalaya region. The material is properly dried, macro-and microscopic evaluation, phytochemical and molecular studies as per the standard quality control and WHO guidelines. Results: The leaves are pinnately lobed, inflorescence compound corymbose. Nonglandular trichomes are uni-seriate, multicellular, and smooth walled; glandular trichomes are bicellular, present throughout the aerial parts. The endodermis is evident in the stem and leaf mesophyll is equifacial. The partial genome sequence analysis showed similarity toward studied species, which can clearly distinguish it from other species of the genus Achillea. The best chromatographic separation was observed with ascentis express C18, 2.7 µm, 100 mm × 4.6 mm. The flavonoids and phenolic acids have shown maximum absorbance at 330 nm. The system suitability parameters such as theoretical plate, tailing factor, and resolution met the acceptance criteria with United States pharmacopeia (USP). Conclusion: The findings of this study will be helpful for the precise identification of the raw drug of A. millefolium from its closely allied species.