Inter-individual Variation in Pain Sensitivity among Healthy Young Indian Adults- a pilot study.

Background Pain perception, with inter-individual variability, is a challenge for both patients and clinicians. Distribution of pain sensitivity parameters being less explored in Indian population can vary with reports from outside India. Objective To describe distribution of pain sensitivity parameters using cold pressor test in healthy adults and to explore relationship of pain sensitivity with gender, vascular reactivity and parental history of hypertension. Method Pain was induced with non-dominant hand immersed in cold water (30 C to 50 C) in 150 subjects (75 males and 75 females) selected as per inclusion and exclusion criteria. Pain sensitivity (pain threshold, tolerance and unpleasantness), vascular reactivity (Δ change in blood pressure and pulse rate) were measured. Result Subjects demonstrated pain threshold [17.6 s (10.7, 26.6)], tolerance [40.2 s (30.0, 59.2)] and unpleasantness [7.0 (6.1,8.0)]. Pain unpleasantness showed a weak negative correlation with pain threshold and tolerance (p < 0.001). Pain threshold had moderate positive correlation with tolerance (p < 0.001). Males had significantly higher pain threshold and tolerance than females (p=0.004). Significant rise in posttest systolic and diastolic blood pressure (p < 0.001), decrease in pulse rate (p=0.007) were found compared to resting values. Pain tolerance showed a weak positive correlation with Δ systolic blood pressure (p=0.039). Subjects with positive parental history of hypertension showed higher pain unpleasantness scores (p=0.02). Conclusion The study demonstrated a wide range of pain sensitivity for narrow age and body mass index. Gender difference was observed for pain threshold and tolerance. Vascular reactivity was demonstrated. Subjective pain perception was higher in subjects with parental history of hypertension.

A novel benzothiophene incorporated Schiff base acting as a "turn-on" sensor for the selective detection of Serine in organic medium.

A novel fluorogenic sensor N-benzo[b]thiophen-2-yl-methylene-4,5-dimethyl-benzene-1,2-diamine (BTMPD) was synthesized and characterized by using spectroscopic methods including UV-visible, FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The designed fluorescent probe, owing to its remarkable properties, behaves as an efficient turn-on sensor for the sensing of amino acid Serine (Ser). Also, the strength of the probe enhances upon the addition of Ser via charge transfer, and the renowned properties of the fluorophore were duly found. The sensor BTMPD shows incredible execution potential with respect to key performance indicators such as high selectivity, sensitivity, and low detection limit. The concentration change was linear ranging from 5 × 10-8 M to 3 × 10-7 M, which is an indication of the low detection limit of 1.74 ± 0.02 nM under optimal reaction conditions. Interestingly, the Ser addition leads to an increased intensity of the probe at λ = 393 nm which other co-existing species did not. The information about the arrangement and the features of the system and the HOMO-LUMO energy levels was found out theoretically using DFT calculations which is fairly in good agreement with the experimental cyclic voltammetry results. The fluorescence sensing using the synthesized compound BTMPD reveals the practical applicability and its application in real sample analysis.

Crystal structure, DFT studies, Hirshfeld surface and energy framework analysis of 4-(5-nitro-thiophen-2-yl)-pyrrolo [1, 2-a] quinoxaline: A potential SARS-CoV-2 main protease inhibitor.

The title compound 4-(5-nitro-thiophen-2-yl)-pyrrolo[1,2-a] quinoxaline (5NO2TAAPP) was obtained by a straightforward catalyst-free reaction of 5-nitro-2- thiophene carboxaldehyde and 1-(2-aminophenyl) pyrrole in methanol and was structurally characterized by FT IR, UV-Vis, NMR spectroscopic techniques and elemental analysis. The structure of the compound has been confirmed by the single-crystal X-ray diffraction technique. The compound crystallizes in a monoclinic crystal system with space group P21/c. Unit cell dimensions: a = 12.2009(17) A0, b = 8.3544(9) A0, c = 13.9179(17) A0 and ß = 104.980(5) A0. Hirshfeld surface analysis was carried out to understand the different intermolecular interactions. The two-dimensional fingerprint plot revealed the most prominent interactions in the compound. Theoretical calculations were executed using Density functional theory (DFT) by Gaussian09 software to develop optimized geometry and frontier molecular orbital analysis. Molecular docking studies revealed that the title compound is a potent inhibitor of Main protease 3CLpro with PDB ID: 6LU7, the viral protease which is responsible for the new Corona Virus Disease (COVID-19).

Effects of repeated exposures to experimental cold pain stimulus on pain perception in healthy young Indian men.

Background: The influence of repeated exposures to cold pain stimulus, a surrogate of clinical pain, has remained largely unexplored. The study was planned to test the effect of repeated exposures to cold pain through cold pressor task on pain sensitivity and vascular reactivity. Methods: Single-group experimental study. Thirty-seven healthy male volunteers (18-25 years) were exposed to cold pressor tasks for seven consecutive days and on the 14th day on the nondominant hand. The same was repeated on dominant hand on first and seventh days; 31 completed the protocol. Results: Pain threshold and tolerance in the nondominant hand increased from day 1 to day 7 (p < 0.001) and were positively correlated on day 1 ( ρ =0.45, p = 0.011) and day 7 ( ρ =0.38, p = 0.036). Diastolic blood pressure response was found to increase by day 7 (p < 0.0024) and positively correlated with tolerance. On the dominant hand, the threshold reduced from day 1 to day 7, while tolerance increased. Both threshold and tolerance remained lower than that of nondominant hand. Day 14 values of threshold and tolerance were in between day 1 and day 7 values but not significantly different from both. Conclusion: Habituation in pain threshold and tolerance was observed on repeated exposure to cold pain, which was not significantly retained till the 14th day. The same was not observed with subjective feeling of pain perception. The increased diastolic blood pressure response is suggestive of peripheral vasoconstriction. Increased tolerance in the dominant hand by day 7 demonstrates a systemic effect in habituation.

Long-term outcome of hyperthyroidism diagnosed in childhood and adolescence: a single-centre experience.

Background The objective of the study was to evaluate the long-term outcome of paediatric-onset hyperthyroidism with follow-up into adulthood and to identify any early predictors of a need for definitive therapy (DT). Methods In a retrospective analysis of patients diagnosed with hyperthyroidism under the age of 18 years and at follow-up, a comparison was made by categorising them into those who underwent definitive therapy (DT group), i.e. thyroidectomy/radioactive iodine (RAI), those who remained on antithyroid drugs (ATD) (CBZ group) and those who had complete remission (RE group). Results Sixty-one (49 females, 12 males) patients with a median age of 15.1 years (range: 3.6-18) at diagnosis were studied. The duration of the first course of ATD varied from <1 year (7%), 1-2 years (26%), >2 years (46%) and ATD never discontinued (21%). Disease relapsed in 69% of patients with <1 year of ATD vs. 79% with >2 years of ATD. At follow-up, the median duration since diagnosis was 8.75 years (range 2.0-20.7 years) and the median age at follow-up was 23.2 years (8-36 years). Thirty-three percent (20/61) had undergone DT (DT group) - with 16.5% (n=10) on RAI and 16.5% (n=10) on surgery, 36% (22/61) were on ATD (CBZ group), whilst 32% (19/61) had undergone full remission (RE group). The comparison did not identify any statistically significant difference for predictor factors at diagnosis including age, T4 and free T4 levels, thyroid peroxidise antibody levels (TPO) and the duration of the first course of carbimazole (CBZ) treatment. Conclusion Long-term complete remission of paediatric-onset hyperthyroidism in our study was 31%. There were no predictors identified that could help predict the long-term outcome, especially into adulthood.

Integrating Ethics into the Physiology curriculum: a scale-up study in three medical colleges in Karnataka, South India.

A published pilot study showed the feasibility of integrating ethics into physiology in a single medical college. However, questions were raised about feasibility of scale-up and acceptance across different colleges. To assess feasibility of integrating ethics into Physiology, first year MBBS students of three medical colleges (n=449, College A=149; 59M, 90F; College B=150; 78M, 72F; College C=150; 48M, 102F) were exposed to the integrated ethics programme. Triggers related to theory or practicals were included. Faculty volunteers conducted the sessions with feedback from observers and students. Students across three colleges felt that the programme was relevant (92%-98%), effectively integrated (86%-98%) [significantly greater number of College A students: (p=0.003)], seldom interfered with physiology teaching (59%-66%). Greater number of students from College C followed by College B and A opined to continue the integrated programme for future years (p=0.004). A scale-up study of integration of ethics programme across different colleges was perceived to be feasible by students and observers.

Early clinical exposure through a vertical integration programme in physiology.

Background: Early clinical exposure is likely to be beneficial during the preclinical year. This pilot programme aimed to define a learning framework of introducing first year medical students to early clinical exposure through a vertical integration programme in the physiology course. The intent was to enhance the understanding of theoretical concepts and practical applications of physiology. Student and faculty perceptions were evaluated. Methods: First year MBBS students (n = 60) had bedside clinics conducted by 5 clinical departments, where the clinical context and applied physiological concepts were emphasized. Clinical sessions were synchronized with pedagogic highlights on related physiological concepts. The student's perceptions were recorded through a semi-structured questionnaire, while qualitative feedback was obtained from the faculty. Results: All students ( 100%) reported that the programme was relevant and did not interfere with their physiology course. Most (91%) appreciated the synchronization of classroom knowledge with clinical exposures, and thought that integrated teaching helped in better understanding of practical applications of physiology (94%) with adequate discussions during the sessions (91 %). Fifty-nine (98%) students preferred integrated teaching over the isolated traditional classroom teaching. The clinicians involved also felt that the early clinical exposure was relevant. The students achieved a mean (SD) score of 13 (2.98) of 25 in the quiz consisting of multiple-choice questions that attempted to test their learning through early clinical exposures. Conclusion: This pilot exercise showed the utility of early clinical exposure integrated into the physiology course. It will be worthwhile to replicate this exercise at other institutions and among a larger student strength.

Introducing a molecular basis to physiology in undergraduate medical education.

Background: Medical professionals in India need to understand the concepts of molecular genetics to stay up-to-date with clinical care as well as to strengthen basic research in the biomedical sciences. Methods: We introduced a modular course on 'Fundamentals in molecular and cellular biology' for first-year medical undergraduate students in the second semester of the first MBBS year in 2015, as part of 'Innovations in teaching physiology' at St John's Medical College. This was a voluntary, add-on course with didactic lectures, hands-on practical classes and a research paper presentation. Evaluation of students' performance in the course took into account their performance in the research paper presentation-based group activity and their attendance for the hands-on practical sessions. Feedback on the content, delivery, evaluation and future improvements of the course was sought from the students. Results: About 65% of students regularly attended the 10-hour long course. Of the students evaluated for the course, 43% achieved the highest, and 11% achieved the lowest grade assigned. Nearly 72% of the students provided feedback on the course. Conclusion: This first outing of the modular course on 'Fundamentals in molecular and cellular biology' generated excitement among the students and achieved some learning for them. It also brought to light hidden challenges in conducting such a voluntary course for medical students in India. Our experience with the course will help in designing a better-integrated course for exposure of first-year medical students to advances in molecular biology and its applied aspects as they progress through the MBBS course.

On the integration of Ethics into the Physiology curriculum.

A one-day state-level workshop was organised in Karnataka to share the experience of a programme implemented earlier, in 2015-16, at St John's Medical College, Bengaluru that integrated the teaching of ethics into the physiology curriculum. The aim was to develop the programme further, list the challenges likely to be faced while scaling it up, and identify other colleges which could participate in the scaling up. Twenty-eight participants, representing 13 medical colleges, and five resource persons attended the workshop. There was a consensus that the integration of ethics into the physiology course was relevant and desirable, although the participants identified several critical challenges which might arise. These included the lack of institutional support, a possible lack of student "buy-in" since it was beyond the requirements of the examinations, and time constraints. Specific areas of integration were identified. Three medical colleges, including the host institution, opted to implement the programme and refine it further.

Exposure to Repeated Mini-objective Structured Practical Examinations as A Formative Assessment Tool to the Students and Faculty in Physiology Practicals.

The study aimed to look at the influence of mini-Objective Structured Practical Examinations (OSPEs) as a formative assessment tool for students and teachers. All first year MBBS students of 2013-14 batch of St. John's Medical College (n=60) went through four mini-OSPE sessions consisting of 5 sets of 6 stations each during 3 months of hematology practicals and final OSPE after 2 months. Feedback of the students and faculty was obtained. The students were categorized into tertiles based on the cumulative scores obtained in the first three-OSPEs and final-OSPE session and were significantly associated from Chi square test. [c2(4, N=54) =15.2, p=0.004]. Low performers with high probability of performing poorly were recognized early in the term. High performers largely remained so and mid performers showed highly variable performance. The feedback obtained supported the role of OSPE as a formative assessment tool. Thus, OSPE could be used as a formative tool for students and teachers.

Mandibular facial talon cusp: a rare case report.

Talon cusp (TC) is a relatively uncommon developmental anomaly characterized by cusp-like projections from the cemento-enamel junction to a variable distance toward the incisal edge of an anterior tooth. It usually presents on palatal/lingual surface of the anterior teeth. Studies have revealed that it consists of enamel, dentine and a variable amount of pulp tissue. Presence of this cusp on the facial surface of an anterior tooth is a rare finding with very few cases being reported in the literature. The effects of TCs are mainly aesthetic and functional. The management requires a sufficient knowledge of the present clinical entity and the problems associated with it. Early detection and treatment plays a very vital role in avoiding the future complications. The present case reports a 25-year-old male patient with a facial TC on the mandibular left central incisor in which a prophylactic enameloplasty was carried out to avoid the stagnation of debris and stain.

The effect of vocal and instrumental music on cardio respiratory variables, energy expenditure and exertion levels during sub maximal treadmill exercise.

The purpose of the study was to investigate the effect of vocal and instrumental music on various physiological parameters during submaximal exercise. Each subject underwent three sessions of exercise protocol without music, with vocal music, and instrumental versions of same piece of music. The protocol consisted of 10 min treadmill exercise at 70% HR(max) and 20 min of recovery. Minute to minute heart rate and breath by breath recording of respiratory parameters, rate of energy expenditure and perceived exertion levels were measured. Music, irrespective of the presence or absence of lyrics, enabled the subjects to exercise at a significantly lower heart rate and oxygen consumption, reduced the metabolic cost and perceived exertion levels of exercise (P < 0.05). There was faster recovery of systolic and diastolic blood pressures and exertion levels during the post exercise period. Music having a relaxant effect could have probably increased the parasympathetic activation leading to these effects.

Anticonvulsant activity of raw and classically processed Vacha (Acorus calamus Linn.) rhizomes.

The rhizome of Vacha (Acorus calamus) has been used in Ayurvedic medicine for the treatment of various ailments, such as epilepsy, headache, eye disorders, insomnia, loss of memory, etc. Previous studies demonstrated that Vacha rhizome is having significant anticonvulsant activity against various induced seizures models in experimental animals. Ayurvedic pharmacopoeia of India has advocated Shodhana (purificatory procedures) to be done prior to its use. In the present study a comparative anticonvulsant activity of raw and Shodhita (classically processed) Vacha rhizomes were screened against Maximal Electro Shock (MES) seizure model to assess the effect of classical purificatory procedure on pharmacological action of Vacha. Phenytoin was used as standard antiepileptic drug for comparison. Pretreatment with both raw and classically processed Vacha samples exhibited significant anticonvulsant activity by decreasing the duration of tonic extensor phase. Further classically processed Vacha statistically decreased the duration of convulsion and stupor phases of MES-induced seizures. The results obtained from the present study clearly confirmed the anticonvulsant activity of raw Vacha and subjecting to classical Shodhana procedure did not alter the efficacy of Vacha rhizomes instead it enhanced the activity profile of the Vacha.

Drug interaction of levothyroxine with infant colic drops.

Infacol (Forest Laboratories UK, Kent, UK) is a widely available over-the-counter preparation used to relieve colic symptoms in neonates and infants. The active ingredient is simeticone. No drug interactions with simeticone are documented in the current summary of product characteristics. The authors report the case of an infant with confirmed congenital hypothyroidism on levothyroxine who experienced a possible drug interaction with simeticone. Despite adequate levothyroxine dosage, thyroid stimulating hormone (TSH) was high, suggesting undertreatment. Questioning revealed the child was taking Infacol drops before feeds while on levothyroxine. The colic drops were immediately discontinued and TSH promptly normalised with a reduction in thyroxine requirement to an age appropriate dosage. Drug interaction of thyroxine with simeticone has not been reported previously and is not listed in the British National Formulary for Children. Clinicians and parents need to be aware of this interaction to avoid unnecessary undertreatment and prevent potential long-term neurological sequelae.

Study on the diuretic activity of Euphorbia fusiformis Buch.-Ham. in albino rats.

The present study was undertaken to evaluate diuretic activity of Euphorbia fusiformis root powder in Wistar strain albino rats. Randomly selected animals were divided into three groups of six animals each. The root powder was suspended in distilled water and administered orally at a dose of 90 mg/kg therapeutically equivalent dose (TED) and 180 mg/kg (TED × 02) to overnight fasted rats. The diuretic activity was evaluated by determination of urine volume and urinary electrolyte concentrations. Test drug showed significant increase in urine volume and urinary electrolyte excretion in a dose-dependant manner. Thus, from this study, it can be concluded that roots of E. fusiformis possess diuretic activity.

Effect of different musical tempo on post-exercise recovery in young adults.

The role of music in increasing the exercise performance is well recognised. There is very little information about effect of music on time taken for post exercise recovery. We examined the effect of music and different musical tempo on post exercise recovery time, following treadmill work. 30 volunteers (15 male, 15 female) subjected to isotonic exercise (submaximal treadmill work) on three consecutive days. They were allowed to rest in silence on the first day, rest by hearing slow music on second day and rest with fast music on third day. Parameters such as Pulse rate, blood pressure, rating of perceived exertion (RPE) were measured at predetermined intervals. Repeated measures ANOVA test showed that with slow music, recovery time of systolic blood pressure (SBP) (7.9 +/- 2.5), diastolic blood pressure (DBP) (5.5 +/- 3.4) pulse rate recovery (PR) (8.0 +/- 2.3) and recovery from exertion (RPE) (7.7 +/- 2.5) were significantly faster when compared to both no music and fast music. The individual music preference made no significant difference in the relaxation time. The study concluded that music hastens post exercise recovery and slow music has greater relaxation effect than fast or no music, recovery time being independent of the gender and individual music preference.

Critical analysis of herbs acting on Mutravaha srotas.

Ayurveda has given prime importance to Mutravaha srotas (urinary system) and Srotogata Vikaras (urinary disorders). Being a system responsible for homeostasis of fluids in the body it also detoxifies the body by eliminating certain waste products through urine. When diseased, people produce symptoms such as, increased or decreased urine production, painful maturition, formation of stones, and thereby obstructed micturition, increased frequency of micturition, and so on. There are many herbs with varied actions specifically aimed at mitigating urinary system disorders. Drugs such as Jambu, Amrasthi, and the like, reduce the increased flow of urine, and hence, are considered as Mutrasangrahaneeya, whereas, drugs like Ikshu, Kustha, and so on, increase the flow of urine, and hence, are considered as Mutravirechaneeya. There are drugs like Padma, Utpala, and so on, which impart normal color to the urine and are known as Mutravirajaneeya dravyas. Asmarighna dravyas break down the calculi and remove them through the urine. These dravyas, when used under proper direction, help in relieving the pain and apathy caused by the disease.

Antipyretic activity of Guduchi Ghrita formulations in albino rats.

The present pharmacological investigation was undertaken to study the anti-pyretic activity of Guduchi ghrita formulations in albino rats against yeast induced pyrexia. Seven groups of six animals were used for the experiment. The yeast induced pyrexia method was standardized first by injecting 12.5% yeast suspension (s.c) followed by recording the rectal temperature at regular intervals. Then the evaluation of anti-pyretic activity of Guduchi ghrita formulations was carried out by using this standard procedure. Both the Guduchi ghrita samples including vehicle significantly attenuated the raise in temperature after three hours of yeast injection. After 6 and 9 hours of yeast injection also both the Guduchi ghrita samples attenuated the raise in temperature in a highly significant manner in comparison to both yeast control and vehicle control groups. The data generated during study shows that both the Guduchi ghrita formulations having significant anti-pyretic activity.

Effect of surgical stress on neutrophil function.

The present study was undertaken to find out the effect of surgical stress on nonspecific immune response. Twenty patients posted for various elective surgeries participated in the study (male : 17, female : 3, age : 43.4 +/- 2 yrs). The blood samples were taken preoperatively (4 to 6 days prior to surgery) and the following parameters were assessed: phagocytic index of neutrophils, avidity index of neutrophils and percentage of neutrophils in differential count. These were compared with the respective parameters assessed in the blood samples taken 24 hours after surgery. There was a significant (P = 0.0001) decrease in the phagocytic index of neutrophil and a significant (P = 0.003) increase in the percentage of neutrophils in differential count in the postoperative blood samples. However, the avidity index did not show a significant change. It could be tentatively concluded that surgical stress causes depression of nonspecific immunity in the early postoperative period.

Growth impairment and adrenal suppression on low-dose inhaled beclomethasone.

Growth impairment and adrenal suppression secondary to inhaled corticosteroids (ICS) is a well-recognised phenomenon. We report a 13-year-old boy, treated long-term for asthma, who presented with short stature while on low-dose inhaled corticosteroid (beclomethasone 200 microg/d). Investigations revealed evidence of severe adrenal suppression. Weaning off the steroid treatment resulted in recovery of adrenal activity and rapid growth. While low-dose ICS are normally considered to have few side effects, this case illustrates the extreme variability of individual sensitivity and the need for careful surveillance of all children treated with long-term steroids.