Influence of information source regarding COVID-19 knowledge among the undergraduate dental students during the early lockdown: a multi-national study.

OBJECTIVE: To assess the influence of information sources on the knowledge regarding COVID-19 among undergraduate dental students in India, Saudi Arabia, Malaysia, and Turkey. SUBJECTS AND METHODS: An online questionnaire in a Google form link was circulated among the target population via various online platforms. It consisted of 14 close-ended questions assessing these students' knowledge and source of COVID-19-related information. SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) was used to compute descriptive statistics, Chi-square test, independent t-test, and ANOVA tests for comparing various variables, and a p-value<0.05 was considered statistically significant. RESULTS: The study yielded 809 responses from dental undergraduate students from India, Saudi Arabia, Malaysia, and Turkey. Dental students from Turkey reported a higher mean knowledge score of 7.91±1.34 and 7.88±0.58 for Malaysian dental students. In contrast, the lower scores were achieved by Saudi Arabia (7.36±1.22) and India (7.37±1.21) dental students, and the findings were statistically significant (p<0.05). The study population used various sources to attain information regarding COVID-19. Most respondents (63.1%) utilized information regarding COVID-19 from multiple sources rather than single sources (36.9%). CONCLUSIONS: Reliable and validated information sources resulted in higher knowledge scores. Turkey and Malaysia dental students reported a higher mean knowledge score and the lowest for Saudi Arabia and India dental students. There is increased popularity of social media platforms as information sources.

A comparative study on the influence of third point of reference on condylar guidance settings in a semi-adjustable articulator with lateral cephalographs: An in-vivo study.

AIM: The study aimed to evaluate the effect on condylar guidance values with casts mounted by facebow transfer (Guichet's point as the third point of reference), Bonwill's, and radiographic method. MATERIALS AND METHODS: The dentulous subject's casts were mounted to a semi-adjustable articulator (Artex Type AR) after facebow transfer with Guichet's point as the third point of reference and also by Bonwill's method. Protrusive records made earlier were utilized to program the right and left side condylar guidance value. Two digital lateral cephalograms were made, one in centric relation, and one in protrusion and the condyles were traced and overlapped. The condylar guidance readings obtained by Bonwill's method, facebow transfer, and lateral cephalometric tracings were compared in this study using the SPSS (Version 17.0 Illinois, Chicago, USA) software. RESULTS: The condylar guidance values obtained from Bonwill's and the facebow transfer method (p < 0.001) was lesser than the radiographic method. The values obtained by casts mounted to the Bonwill's method differed significantly (p < 0.001) from the other two methods. CONCLUSION: The values obtained by facebow transfer were closer to the radiographic values whereas the values obtained by Bonwill's method mounting differed markedly.

Good for the lung but bad for the liver? Garlic-induced hepatotoxicity following liver transplantation.

WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio® (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio® was discontinued and liver enzymes normalized. A liver biopsy revealed mild periportal cholestatic reaction suggesting potential drug-induced aetiology. WHAT IS NEW AND CONCLUSION: This is the first description of liver injury secondary to garlic supplementation. Therefore, this garlic supplement should be listed as a potential cause of acute drug-induced liver injury.

Two dosing regimens of certolizumab pegol in patients with active rheumatoid arthritis.

OBJECTIVE: To investigate clinical efficacy and safety of 2 certolizumab pegol (CZP) maintenance dosing regimens plus methotrexate (MTX) in active rheumatoid arthritis (RA) patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) after the CZP 200 mg every 2 weeks open-label run-in period. METHODS: DOSEFLEX (dosing flexibility) was a double-blind, placebo-controlled randomized study with an open-label run-in phase. During the run-in phase, all patients received CZP 400 mg (weeks 0, 2, and 4) and 200 mg every 2 weeks to week 16. Week 16 ACR20 responders were randomized 1:1:1 at week 18 to CZP 200 mg every 2 weeks, 400 mg every 4 weeks, or placebo. RESULTS: A total of 209 (of 333) patients were randomized at week 18 (CZP: 200 mg, n = 70; 400 mg, n = 70; placebo, n = 69). Groups had similar baseline characteristics (week 0). Week 34 ACR20 response rates were comparable between the CZP 200 mg every 2 weeks and the 400 mg every 4 weeks groups (67.1% versus 65.2%), which was significantly higher than placebo (44.9%; P = 0.009 and P = 0.017). ACR50/70 and remission criteria were met more frequently in CZP groups than placebo at week 34, with similar responses between anti-tumor necrosis factor-experienced and naive patients. Improvements from baseline Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and Health Assessment Questionnaire disability index scores were maintained in CZP groups from week 16 to 34 while worsening on placebo. Adverse event (AE) rates in the double-blind phase were 62.9% versus 60.9% versus 62.3%; serious AE rates were 7.1% versus 2.9% versus 0.0% (CZP 200 mg, 400 mg, and placebo groups). CONCLUSION: In active RA patients with an incomplete MTX response, CZP 200 mg every 2 weeks and 400 mg every 4 weeks were comparable and better than placebo for maintaining clinical response to week 4 following a 16-week, open-label run-in phase.

Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene.

Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r²≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

Smoking among Saudi university students: consumption patterns and risk factors.

Tobacco use is increasing among young people, especially in Gulf nations such as Saudi Arabia. The objectives of this study were to estimate the prevalence and behavioural patterns of tobacco use among undergraduate students at King Saud University, Riyadh, Saudi Arabia during the academic year 2008/09 and investigate factors that influenced their tobacco use. A cross-sectional study was done of a representative sample (n = 6793) of the undergraduate student population using a modified version of the global youth tobacco survey questionnaire. The prevalence of smoking was 14.5% among students, 22.2% and 2.2% among fathers and mothers and 43.1% and 14.8% for male and female siblings; 15.0% reported all or most of their friends smoked. The most important independent predictors of smoking were: friends' smoking (some: OR = 6.7 and all: OR = 54.9), sister's smoking (OR = 2.2), mother's smoking (OR = 2.1), single status (OR = 1.7) and age (OR = 1.18).

Formulation and evaluation of s-(-)-amlodipine besylate and nebivolol hydrochloride tablets.

The objective of the present study was to develop a tablet formulation of S-(-)-amlodipine besylate chiral separation drug and nebivolol hydrochloride for better management of hypertension, while reducing or avoiding undesirable adverse effects, which are often associated with administration of a racemic mixture of amlodipine. The composition containing the optically pure S-(-)- isomer of amlodipine 2.5 mg has calcium channel blocking activity and, nebivolol hydrochloride 5 mg has beta-receptor blocking activity.The study was also carried out to design a suitable dissolution medium for S-(-) - amlodipine besylate and nebivolol hydrochloride. Amlodipine besylate and nebivolol hydrochloride had maximum solubility in pH 1.2 and thus pH 1.2 was selected as the most suitable media for S-(-) - amlodipine besylate and nebivolol hydrochloride dissolution studies. The RSD below 2% indicated insignificant batch-to-batch variation. The accelerated stability study of the optimized formulation was performed as the ICH guidelines. The results indicated no change in optical rotation of S-(-) - amlodipine besylate. Hence, combination of two drugs can be formulated into the tablet by wet granulation technique having satisfactory release profile.

From drug target to leads--sketching a physicochemical pathway for lead molecule design in silico.

The discovery of new pharmaceuticals via computer modeling is one of the key challenges in modern medicine. The advent of global networks of genomic, proteomic and metabolomic endeavors is ushering in an increasing number of novel and clinically important targets for screening. Computational methods are anticipated to play a pivotal role in exploiting the structural and functional information to understand specific molecular recognition events of the target macromolecule with candidate hits leading ultimately to the design of improved leads for the target. In this review, we sketch a system independent, comprehensive physicochemical pathway for lead molecule design focusing on the emerging in silico trends and techniques. We survey strategies for the generation of candidate molecules, docking them with the target and ranking them based on binding affinities. We present a molecular level treatment for distinguishing affinity from specificity of a ligand for a given target. We also discuss the significant aspects of drug absorption, distribution, metabolism, excretion and toxicity (ADMET) and highlight improved protocols required for higher quality and throughput of in silico methods employed at early stages of discovery. We present a realization of the various stages in the pathway proposed with select examples from the literature and from our own research to demonstrate the way in which an iterative process of computer design and validation can aid in developing potent leads. The review thus summarizes recent advances and presents a viewpoint on improvements envisioned in the years to come for automated computer aided lead molecule discovery.

Secretion of interleukin-1beta and interleukin-6 by fragments of term human placental villi: signalling pathways and effects of tumour necrosis factor alpha and mode of delivery.

The regulation of cytokine secretion has not been extensively investigated in placental tissue. Fragments of term human placenta were incubated in Tyrode's medium for 3h and cytokine concentrations were measured in the supernatant. IL-1beta secretion after vaginal delivery (VD) was (mean +/- SEM fmol/mg wet weight/3h) 0.193 +/- 0.005 (basal) and 0.549 +/- 0.18 (+1n M TNFalpha) and was more sensitive to TNFalpha dose after elective Caesarean section in the absence of clinical labour (CS) than VD. Secretion of IL-6 after VD was 2.3 +/- 0.47 (basal) and 3.01 +/- 0.34 (+1n M TNFalpha), was correlated with the secretion of IL-1beta and was more sensitive to TNFalpha dose after VD than CS. The inhibitors SB203580, PD98059, SN50, cycloheximide and D-ribofuranosylbenzimidazole each reduced the basal and TNFalpha-stimulated secretion of IL-1beta and also reduced IL-6 secretion with the exception of SN50. There were no interactions between effects of inhibitors and mode of delivery or TNFalpha. In summary we found that term placenta spontaneously secretes IL-1beta and IL-6 in vitro. Delivery after labour alters placental sensitivity to TNFalpha. Exposure to agents known to inhibit MAPK pathways, NF-kappaB, or synthesis of protein and mRNA reduces placental cytokine secretion.

A randomized trial of glyceryl trinitrate ointment and nitroglycerin patch in healing of anal fissures.

Mean maximum anal resting pressure is directly related to the activity of the smooth muscles of the internal and external sphincters and has been found to be increased in the patients of anal fissure. It has been shown that blood flow at the posterior midline of anoderm is inversely related to the mean maximum anal resting pressure, and topical application of glyceryl trinitrate (GTN) ointments is a very successful treatment. This randomized study was designed to evaluate the relative value of a nitroglycerin patch applied at a distance from the fissure site in healing anal fissure compared to GTN ointment and compared to surgical treatment. Forty-two consecutive patients with chronic anal fissure of more than 4 months' duration were randomized into two equally sized groups: those in group A received 0.2% GTN ointment while those in group B received a 10-mg nitroglycerin patch for 8 weeks. Patients were also asked to rate their pain intensity on a scale of 0-10. Five patients were excluded for various reasons; results were analyzed for the remaining 37 patients (group A, n=18; group B, n=19). A control group C consisted of 12 patients who underwent surgical treatment. Fissures healed completely in 12 of 18 (66.7%) patients in group A, 12 of 19 (63.2%) in group B and 11/12 (91.7%) in group C. The healing rates in groups A and B did not differ significantly (P=0.7), nor was there a difference between these and surgical group C (P=0.13). The local application of GTN ointment and the nitroglycerin patch are both effective, economical, and alternative treatment options for most patients with anal fissures.

Characterization of a thermostable extracellular beta-galactosidase from a thermophilic fungus Rhizomucor sp.

An extracellular beta-galactosidase from a thermophilic fungus Rhizomucor sp. has been purified to homogeneity by successive DEAE cellulose chromatography followed by gel filtration on Sephacryl S-300. The native molecular mass of the enzyme is 250,000 and it is composed of two identical subunits with molecular mass of 120,000. It is an acidic protein with a pI of 4.2. Purified beta-galactosidase is a glycoprotein and contains 8% neutral sugar. The optimum pH and temperature for enzyme activity are 4.5 and 60 degrees C, respectively. The enzyme is stable at 60 degrees C for 4 h, and has a t(1/2) of 150 min(-1) at 70 degrees C which is one of the highest reported for fungal beta-galactosidases. Substrate specificity studies indicated that the enzyme is specific for beta-linked galactose residues with a preference for p-nitrophenyl-beta-D-galactopyranoside (pNPG). The Km and Vmax values for the synthetic substrates pNPG and o-nitrophenyl-beta-D-galactopyranoside (oNPG) were 0.66 mM and 1.32 mM; and 22.4 mmol min(-1) mg(-1) and 4.45 mmol min(-1) mg(-1), respectively, while that for the natural substrate, lactose, was 50.0 mM and 12 mmol min(-1) mg(-1). The end product galactose and the substrate analogue isopropyl thiogalactopyranoside (ITPG) inhibited the enzyme with Ki of 2.6 mM and 12.0 mM, respectively. The energy of activation for the enzyme using pNPG and oNPG were 27.04 kCal and 9.04 kCal, respectively. The active site characterization studies using group-specific reagents revealed that a tryptophan and lysine residue play an important role in the catalytic activity of the enzyme.

Comparison of the ages of tachycardia onset in patients with atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia.

Atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia may have different ages of tachycardia onset. Symptom onset data were obtained in 519 patients (atrioventricular nodal reentrant tachycardia, 231, accessory pathway-mediated tachycardia, 288). The mean age of the patients at the time of evaluation was 47 +/- 17 years (atrioventricular nodal reentrant tachycardia) and 37 +/- 15 years (accessory pathway-mediated tachycardia). The mean age of symptom onset was 32 +/- 18 years for atrioventricular nodal reentrant tachycardia and 23 +/- 14 years for accessory pathway-mediated tachycardia. A significantly greater proportion of patients with atrioventricular nodal reentrant tachycardia had the initial onset of symptoms after the age of 20 years (atrioventricular nodal reentrant tachycardia, 67% vs accessory pathway-mediated tachycardia, 41%, p < 0.001). In summary, there is a different mean age of symptom onset for patients with atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia.

Chitinolytic enzymes: their contribution to basic and applied research.

After cellulose, chitin is the second most abundant renewable resource available in nature. Marine invertebrates and fungal biomass are the two main sources of chitinous waste, which is commercially exploited. The enzymes involved in chitin degradation have been particularly well studied. Such enzymes have applications in ultrastructural studies, in the preparation of chitooligosaccharides which show anti-tumour activity, as biocontrol agents and in single-cell protein production. Here, the contribution chitin enzymology can make to basic and applied research is discussed.

Biotin-reversible neurodegenerative disease in infancy.

Two siblings with consanguineous parents began having myoclonic jerks at age 5 months after introduction of mixed feeding. There was later developmental regression. The elder girl died without diagnosis aged 1 year, after prolonged continuous hyperventilation. The younger sibling did not have metabolic acidosis when first investigated for myoclonus and hypotonia aged 5 months. At 9.5 months, when intermittently decerebrate and hyperventilating, she had a metabolic acidosis with elevated blood lactic, pyruvic and beta-hydroxybutyric acids, and beta-hydroxyisovaleric aciduria. On the assumption that she had beta-methylcrotonyl-CoA carboxylase deficiency she was started on biotin, 10 mg daily. Within 36 h there was dramatic clinical and biochemical improvement. Previously defective eye movement control and gaze became normal, hyperventilation ceased, and excessive organic acid excretion in urine was abolished. She remains on long-term biotin and at age 2 years her development appears normal in all respects. Fibroblast culture however revealed normal quantities of the enzymes beta-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase. Irrespective of niceties of enzyme and organic acid biochemistry, the clinician must be aware of biotin-reversible regressive brain disease which may present before manifest metabolic acidosis.

Pharmacologic induction of luteolysis in cynomolgus monkeys (Macaca fascicularis).

Earlier studies reported from this laboratory demonstrated the luteolytic effect of a 5-day sequential regimen of 3 days of estrogen overlapped with 3 days of PGF2 alpha administered during the midluteal phase to cynomolgus monkeys. In this study, a different regimen, containing estrogen, lower doses of PGF2 alpha, and methylergonovine maleate (MEM), was used. Individual components of this modified sequential regimen were not effective as luteolytic agents. When 3 days of estrogen (40 micrograms of depoestradiol cypionate [DEC] on the first day and 40 micrograms of estradiol benzoate [EB] on second and third day) was followed by 3 days of MEM (400 micrograms, twice daily) overlapping 1 day of estrogen treatment, there was a significant shortening of the length of the menstrual cycle (less than 26 days) in eight of 10 animals, with a concomitant decline in plasma levels of progesterone. When a low dose of MEM (100 micrograms, twice daily), which was completely ineffective in shortening cycle lengths with the same estrogen treatment, was administered alternately with PGF2 alpha (5 mg twice daily, 11 of 14 animals had shortened cycles, with an associated decline in levels of progesterone. PGF2 alpha and MEM without the estrogen pretreatment did not have a significant effect on cycle lengths or blood levels of progesterone, thus demonstrating a synergism between estrogen and the other compounds in inducing luteolysis. Since the agents used in these sequential regimens have potent effects on the uterus, the treatments were repeated in hysterectomized monkeys to determine whether the uterus was involved in the mediation of luteolysis. These treatments caused a significant drop in plasma levels of progesterone by the tenth day after the preovulatory estrogen peak, thus demonstrating that the uterus is not essential to the luteolytic action.

Concentrations of oestradiol-17beta and progesterone in the peripheral plasma of the cynomolgus monkey (Macaca fascicularis) in relation to the length of the menstrual cycle and its component phases.

Ninety-three female cynomolgus monkeys were monitored throughout 647 menstrual cycles; 93.2% of these cycles were 22--37 days long and were normally distributed, with a mean of 29.2 days. Menstrual bleeding generally lasted for 3--5 days and was not related to the length of the cycle. The levels of progesterone and oestradiol-17beta in the plasma were measured during the menstrual cycle in 30 monkeys. The concentration of oestradiol-17beta reached a mid-cycle peak on day 11 or 12 of the cycle. The interval between the beginning of the cycle and the oestrogen peak was constant; the interval between the oestrogen peak and the end of the cycle increased or decreased with the cycle length. The level of progesterone began to rise at about the time of the oestrogen peak and remained raised for longer periods as the length of the cycle increased. The length of the menstrual cycle, therefore, appeared to be determined by the duration of the increase in the level of progesterone or by the life of the corpus luteum in the luteal phase. The relationship between the lengths of the cycle and the luteal phase can be defined by the expression: cycle length = 12.6 + 0.96 X length of luteal phase (correlation coefficient = 0.875).

Adrenal and ovarian steroid secretion in the rat estrous cycle temporally related to gonadotropins and steroid levels found in peripheral plasma.

This study was undertaken to determine the patterns of estrogen and progestin secretion by the adrenal and the ovary and to relate these to the levels of steroids and gonadotropins found in peripheral plasma. A total of 70 rats were used in this study. Adrenal venous (ADVB) and ovarian venous blood (OVB) were collected by concurrent cannulation and peripheral blood (PB) was obtained from the abdominal aorta. Estrone (E1), estradiol (E2), PROGESTERONE (P) and 17alpha-hydroxyprogesterone (17alpha-OHP) were measured by radioimmunoassay. The concentration of E2 in general was higher in ADVB than in OVB. Although increased levels of E2 in ADVB were found on the afternoon of proestrus (1527-2634 pg/ml), they were not significantly different from those recorded at other times. In contrast E2 in OVB was lowest at 1000-1200 hr of estrus (225 pg/ml) and highest at 1000-2000 hr of proestrus (1190-1605 pg/ml). The E2 in PB followed the pattern seen in OVB; the values ranged from 80-211 pg/ml. P concentration in general was higher in ADVB than in OVB. The lowest concentration of P in ADVB was between 0200-0400 hr of estrus (183 ng/ml) and the highest between 1400-1600 hr of proestrus (580 ng/ml) and 1000-1200 hr of estrus (591 ng/ml). The lowest concentration of P in the OVB was between 1600-1800 hr of diestrus (42 ng/ml) and the highest between 0200-0400 hr of estrus (466 ng/ml). In the PB, P reflected changes in adrenal as well as ovarian secretion; the values ranged fron 7-25 ng/ml. E1 in ADVB was in general lower than in OVB, and there were no significant changes at any stage of the cycle. In the OVB, however, E1 showed a pattern similar to that of E2. Levels of E1 in PB were very low and failed to show any significant changes. 17alpha-OHP was high in ADVB, although there were no significant changes during the cycle; PB levels also did not show any significant changes. In the OVB a peak of 17alpha-OHP was recorded between 0200-0400 hr on the day of estrus. The LH and FSH levels showed increases after 1600 hr on the day of proestrus and this was in agreement with earlier studies. Since the adrenal secretes all of the 4 steroids studied, it is reasonable to assume that it does exert some effect in the pituitary-gonadal axis. A role of adrenal P for the facilitation of the preovulatory LH release has been indicated and the increased secretion of adrenal P between 1400-1600 hr of proestrus supports this possibility.