Design and synthesis of phenoxy methyl-oxadiazole compounds against Alzheimer's disease.

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and ß-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC50 values of 0.120, 0.039, and 0.063 µM, respectively. However, the compounds showed limited effectiveness against BChE, with only a few compounds exhibiting moderate inhibition. Compound 7e showed an inhibitory effect against BACE-1 close to that of the standard drug. Structural analysis revealed that the compounds with substituted benzothiazole and thiazole moieties exhibited the most promising inhibitory activity. This study provides valuable insights into the potential of these synthesized derivatives as a treatment against Alzheimer's disease. Moreover, the structure, stability, and properties of the active compounds were further investigated using density functional theory calculations. As a final note, the utilization of molecular docking and molecular dynamics simulation studies allowed us to elucidate the action mechanism of the active compounds and gain insights into the structure-activity relationship against AChE and ß-secretase proteins. These computational techniques provide valuable information on the binding modes, interactions with target enzymes, dynamic behavior, and conformational changes of the compounds, enabling a comprehensive understanding of their biological activity.

Anesthetic Management of a Patient with MIRAGE Syndrome: A Case Report.

MIRAGE syndrome consists of Myelodysplasia, Infection, Growth restriction, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. We report the uneventful anesthesia management of a 6-year-old female patient with MIRAGE syndrome. We think it can guide anesthesiologists caring for patients with this syndrome to find the appropriate method for them.

Storage, Retention, and Use of Leftover Pathology Specimens: The Underestimated Treasures.

The proper regulations for storage, retention, and use of archived specimens in pathology laboratories and academic institutions are yet to be established. These specimens could be used appropriately for research purposes. Ideal storage and retention in a controlled environment is necessary, and there is a lack of established rules regarding the ownership of the tissue specimens, paraffin blocks, and slides. Though there are numerous uses of formalin-fixed tissue specimens, blocks, and slides, there are also problems in archiving them that hinder their use. This review article addresses the above issues and proposes simple guidelines for the effective use of archived specimens.

Awareness of Tetanus Toxoid Vaccination among Women of Reproductive Age Attending Outpatient Department in a Tertiary Level Hospital.

Maternal and neonatal tetanus is still a major but preventable cause of mortality in many developing countries like Bangladesh. Women of reproductive age are very prone to tetanus infection. This descriptive cross-sectional study was carried out at outpatient department (OPD) of Sir Salimullah Medical College and Mitford Hospital, Bangladesh from October 2019 to April 2020 to determine the level of awareness about Tetanus Toxoid (TT) vaccination in women of reproductive age 15-49 years. Data were collected from 342 women by face to face interview with a semi-structured questionnaire. A large number of the respondents (43.27%) were belonged to 15-24 years age group, majority (92.98%) were Muslim and most of them (41.28%) were SSC passed. A very large number of them (78.36%) were married and (64.55%) had 1-2 children. More than three quarter (78.36%) of women heard about tetanus and 83.96% women thought that tetanus is preventable by TT vaccination. Among the respondents who had heard about tetanus, majority (68.67%) of them had taken TT vaccine, 92.58% of them had taken the first dose before 25 years of age and 71.05% had completed the full course. Regarding awareness of the respondents, 65.79% were aware of risk of neonatal tetanus of an unimmunized mother & 61.19% distinguished that agent of tetanus can be transmitted through wounds. It is considered that the findings of the study will provide a useful basis for further research and planning.

Assessment of Antimicrobial Activity and Cytotoxic Effect of Nigella sativa, Syzygium aromaticum, and Allium cepa Formulation for Use As Antimicrobial Gel or Mouthwash.

BACKGROUND: Black cumin/Nigella sativa is traditionally used for its wide range of medicinal effects. Clove/Syzygium aromaticum is well known as a natural antibiotic with antiviral, antibacterial, and antifungal properties, and onion/Allium cepa for its antibacterial properties. The combination of these extracts can effectively have many therapeutic applications. AIM: The aim of the present study is to prepare the formulation of N. sativa, S. aromaticum, A. cepa and to assess the antimicrobial activity and cytotoxic effect of the prepared formulation. MATERIALS AND METHODS: Antimicrobial activity was carried out by agar well diffusion method and cytotoxic activity was carried out using the brine shrimp lethality assay method. RESULTS: The antimicrobial activity showed the zone of inhibition was highest with Staphylococcus aureus showing 22 mm of zone of inhibition at 100 µl. The cytotoxicity test showed there are about 90% live nauplii in the lowest concentration at 5 µl. CONCLUSION: The study concluded that the combination extract of N. sativa, S. aromaticum, and A. cepa could be used as an antimicrobial agent. Further research with pathogenic oral microorganisms can validate this formulation as an antimicrobial gel or mouthwash for various pathologies.

Gender-based cytomorphometric analysis of buccal exfoliated cells in a South Indian population.

OBJECTIVE: To assess differences based on gender in nuclear area (NA), cytoplasmic area (CA), and nuclear-cytoplasmic ratio (N:C ratio) values for clinically normal buccal smears in apparently healthy subjects of a South Indian population, thereby providing definitive baseline cytomorphometric measurements for the South Indian population. METHODS: Buccal smears were collected from 60 healthy subjects (30 males and 30 females) of a South Indian population above 18 years in age. Values of the NA and CA were measured, and the N:C ratio calculated, using ImageJ software. Statistical analysis of the data with independent t tests and 95% confidence intervals was done using SPSS version 21 (significance set at P < 0.05). RESULTS: The results showed that there were significant differences in the NA, CA, and N:C values between males and females irrespective of age (P = 0.01). CONCLUSION: Definitive gender-specific baseline cytomorphometric data can be established using exfoliative cytology for the South Indian population, and this may be helpful in deciphering the occurrence of oral pre-malignant diseases and oral squamous cell carcinoma in this population, as the incidence of these conditions varies with gender and different ethnic groups.

Synthesis, anticholinesterase activity, molecular docking, and molecular dynamic simulation studies of 1,3,4-oxadiazole derivatives.

Two new series of 1,3,4-oxadiazoles bearing pyridine and thiazole heterocycles (4a-h and 5a-h) were synthesized (2,5-disubstituted-1,3,4-oxadiazoles). The structures of these newly synthesized compounds were confirmed by 1 H nuclear magnetic resonance (NMR), 13 C NMR, high-resolution mass spectrometric and Fourier transform infrared spectroscopic methods. All these compounds were evaluated for their enzyme inhibitory activities against two cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). From the studies, we identified compounds 4a, 4h, 5a, 5d, and 5e as selective AChE inhibitors, with IC50 values ranging from 0.023 to 0.037 µM. Furthermore, docking studies of these compounds were performed at the active sites of their target enzymes. The molecular docking study showed that 5e possessed an ideal docking pose with interactions inside AChE.

Effect of Slow Breathing Exercise on Glycaemic Status in Type 2 Diabetic Male Patients.

Slow breathing exercise (SBE) improves the chronic disease conditions. This study aimed to observe the effects of slow breathing exercise on glycaemic status in male patients with type 2 diabetes mellitus (DM). This prospective interventional study recruited sixty (60) diagnosed male type 2 diabetes mellitus (T2DM) patients aged 45-55 years with disease history 5-10 years, from Out Patients Department (OPD) of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2015 to December 2015. Thirty patients performed SBE for 30 minutes 2 times daily for 3 months (study group) and 30 patients did not perform any breathing exercise (Control) and were under follow up for similar duration. Fasting plasma Glucose (FPG), 2 hours Post prandial plasma glucose (PPPG) and glycosylated haemoglobin (HbA1c%) of all patients were assessed both at baseline and after3 months of study. Independent sample and paired sample t-test were used for statistical analysis. In this study the mean FPG, 2 hrs PPPG and HbA1c significantly (p<0.05) reduced in patients with SBE after 3 months whereas no significant changes in FPG, 2 hours PPPG were observed, moreover HbA1c significantly increased (p<0.01) after 3 months in patients who were not under SBE. This study reveals that slow breathing exercise significantly improves glycagemic status in type 2 diabetic patients.

The global incidence of bullous pemphigoid: a systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. OBJECTIVES: The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. METHODS: Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. RESULTS: Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8-13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2-60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8-18·2) and 5·6 (95% CI 3·5-9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0-29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. CONCLUSIONS: The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.

Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase.

According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a-l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for ß-amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate-enzyme relationship, and a mixed-type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.

Design, synthesis, biological activity, molecular docking, and molecular dynamics of novel benzimidazole derivatives as potential AChE/MAO-B dual inhibitors.

To develop new acetylcholinesterase (AChE)-monoamine oxidase-B (MAO-B) dual inhibitors against Alzheimer's disease, the benzimidazole ring, which has a propargyl side chain with previously proven selective MAO-B inhibitory activity, was used as the main structure. Moreover, like donepezil, it was thought that the enzyme AChE would provide π-π interactions with the peripheral anionic side in this structure. Piperazine derivatives were chosen for the cationic active site. The synthesis of the compounds was carried out in five steps. The structures of the compounds were determined using 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectrometry spectroscopic methods. First, the in vitro AChE, butyrylcholinesterase (BChE), MAO-A, and MAO-B inhibitory potentials of the obtained compounds were investigated. As a result of activity tests, compounds 5b, 5e, 5g, and 5h showed inhibitory activity against AChE; compounds 5e and 5g showed inhibitory activity against MAO-B. None of the compounds showed inhibitory activity against BChE or MAO-A. Compounds 5e and 5g showed dual inhibition. Among these compounds, compound 5g had inhibition potential similar to that of donepezil and selegiline. For compound 5g, further kinetic studies and Aß-plaque inhibitory potentials were investigated using in vitro methods. Molecular docking studies were performed using both AChE and hMAO-B crystals to elucidate the compound's interactions with the enzyme active site. The binding modes of the compound on AChE were fully elucidated by molecular dynamics studies.

Characterization of a Coliphage AS1 isolated from sewage effluent in Pakistan / Caracterização de um colifago AS1 isolado de efluente de esgoto no Paquistão

The emergence of multi-drug resistant (MDR) bacterial strains, which are posing a global health threat has developed the interest of scientists to use bacteriophages instead of conventional antibiotics therapy. In light of an increased interest in the use of phage as a bacterial control agent, the study aimed to isolate and characterize lytic phages from sewage effluent. During the current study, bacteriophage AS1 was isolated from sewage effluent against E.coli S2. The lytic activity of phageAS1 was limited to E.coli S2 strain showing monovalent behavior. The calculated phage titer was 3.5×109 pfu/ml. PhageAS1 was stable at a wide range of pH and temperature. The maximum stability was recorded at 37ºC and pH 7.0, while showing its normal lytic activity at temperature 60ºC and from pH 5.0 to 11.0 respectively. At temperature 70ºC, phage activity was somewhat reduced whereas, further increase in temperature and decrease or increase in pH completely inactivated the phage. From the current study, it was concluded that waste water is a best source for finding bacteriophages against multi-drug resistant bacterial strains and can be used as bacterial control agent.

O surgimento de cepas bacterianas multirresistentes (MDR), que representam uma ameaça global à saúde, desenvolveu o interesse dos cientistas em usar bacteriófagos em vez da terapia convencional com antibióticos. Diante do crescente interesse no uso de fago como agente de controle bacteriano, o estudo visou isolar e caracterizar fagos líticos de efluente de esgoto. Durante o estudo atual, o bacteriófago AS1 foi isolado de efluente de esgoto contra E. coli S2. A atividade lítica de phageAS1 foi limitada à cepa E. coli S2, apresentando comportamento monovalente. O título de fago calculado foi de 3,5 x 109 ufp/ml. PhageAS1 foi estável em uma ampla faixa de pH e temperatura. A estabilidade máxima foi registrada a 37ºC e pH 7,0, enquanto mostrou atividade lítica normal em temperatura de 60ºC e pH 5,0 a 11,0, respectivamente. Na temperatura de 70ºC, a atividade do fago foi um pouco reduzida, enquanto o aumento adicional da temperatura e a diminuição ou aumento do pH inativaram completamente o fago. Com base no estudo atual, concluiu-se que a água residual é a melhor fonte para encontrar bacteriófagos contra cepas bacterianas multirresistentes e pode ser usada como agente de controle bacteriano.

Characterization of a Coliphage AS1 isolated from sewage effluent in Pakistan

Abstract The emergence of multi-drug resistant (MDR) bacterial strains, which are posing a global health threat has developed the interest of scientists to use bacteriophages instead of conventional antibiotics therapy. In light of an increased interest in the use of phage as a bacterial control agent, the study aimed to isolate and characterize lytic phages from sewage effluent. During the current study, bacteriophage AS1 was isolated from sewage effluent against E.coli S2. The lytic activity of phageAS1 was limited to E.coli S2 strain showing monovalent behavior. The calculated phage titer was 3.5×109 pfu/ml. PhageAS1 was stable at a wide range of pH and temperature. The maximum stability was recorded at 37ºC and pH 7.0, while showing its normal lytic activity at temperature 60ºC and from pH 5.0 to11.0 respectively. At temperature 70ºC, phage activity was somewhat reduced whereas, further increase in temperature and decrease or increase in pH completely inactivated the phage. From the current study, it was concluded that waste water is a best source for finding bacteriophages against multi-drug resistant bacterial strains and can be used as bacterial control agent.

Resumo O surgimento de cepas bacterianas multirresistentes (MDR), que representam uma ameaça global à saúde, desenvolveu o interesse dos cientistas em usar bacteriófagos em vez da terapia convencional com antibióticos. Diante do crescente interesse no uso de fago como agente de controle bacteriano, o estudo visou isolar e caracterizar fagos líticos de efluente de esgoto. Durante o estudo atual, o bacteriófago AS1 foi isolado de efluente de esgoto contra E. coli S2. A atividade lítica de phageAS1 foi limitada à cepa E. coli S2, apresentando comportamento monovalente. O título de fago calculado foi de 3,5 x 109 ufp/ml. PhageAS1 foi estável em uma ampla faixa de pH e temperatura. A estabilidade máxima foi registrada a 37ºC e pH 7,0, enquanto mostrou atividade lítica normal em temperatura de 60ºC e pH 5,0 a 11,0, respectivamente. Na temperatura de 70ºC, a atividade do fago foi um pouco reduzida, enquanto o aumento adicional da temperatura e a diminuição ou aumento do pH inativaram completamente o fago. Com base no estudo atual, concluiu-se que a água residual é a melhor fonte para encontrar bacteriófagos contra cepas bacterianas multirresistentes e pode ser usada como agente de controle bacteriano.

Characterization of a Coliphage AS1 isolated from sewage effluent in Pakistan / Caracterização de um colifago AS1 isolado de efluente de esgoto no Paquistão

The emergence of multi-drug resistant (MDR) bacterial strains, which are posing a global health threat has developed the interest of scientists to use bacteriophages instead of conventional antibiotics therapy. In light of an increased interest in the use of phage as a bacterial control agent, the study aimed to isolate and characterize lytic phages from sewage effluent. During the current study, bacteriophage AS1 was isolated from sewage effluent against E.coli S2. The lytic activity of phageAS1 was limited to E.coli S2 strain showing monovalent behavior. The calculated phage titer was 3.5×109 pfu/ml. PhageAS1 was stable at a wide range of pH and temperature. The maximum stability was recorded at 37ºC and pH 7.0, while showing its normal lytic activity at temperature 60ºC and from pH 5.0 to11.0 respectively. At temperature 70ºC, phage activity was somewhat reduced whereas, further increase in temperature and decrease or increase in pH completely inactivated the phage. From the current study, it was concluded that waste water is a best source for finding bacteriophages against multi-drug resistant bacterial strains and can be used as bacterial control agent.

O surgimento de cepas bacterianas multirresistentes (MDR), que representam uma ameaça global à saúde, desenvolveu o interesse dos cientistas em usar bacteriófagos em vez da terapia convencional com antibióticos. Diante do crescente interesse no uso de fago como agente de controle bacteriano, o estudo visou isolar e caracterizar fagos líticos de efluente de esgoto. Durante o estudo atual, o bacteriófago AS1 foi isolado de efluente de esgoto contra E. coli S2. A atividade lítica de phageAS1 foi limitada à cepa E. coli S2, apresentando comportamento monovalente. O título de fago calculado foi de 3,5 x 109 ufp/ml. PhageAS1 foi estável em uma ampla faixa de pH e temperatura. A estabilidade máxima foi registrada a 37ºC e pH 7,0, enquanto mostrou atividade lítica normal em temperatura de 60ºC e pH 5,0 a 11,0, respectivamente. Na temperatura de 70ºC, a atividade do fago foi um pouco reduzida, enquanto o aumento adicional da temperatura e a diminuição ou aumento do pH inativaram completamente o fago. Com base no estudo atual, concluiu-se que a água residual é a melhor fonte para encontrar bacteriófagos contra cepas bacterianas multirresistentes e pode ser usada como agente de controle bacteriano.

Characterization of a Coliphage AS1 isolated from sewage effluent in Pakistan.

The emergence of multi-drug resistant (MDR) bacterial strains, which are posing a global health threat has developed the interest of scientists to use bacteriophages instead of conventional antibiotics therapy. In light of an increased interest in the use of phage as a bacterial control agent, the study aimed to isolate and characterize lytic phages from sewage effluent. During the current study, bacteriophage AS1 was isolated from sewage effluent against E.coli S2. The lytic activity of phageAS1 was limited to E.coli S2 strain showing monovalent behavior. The calculated phage titer was 3.5×109 pfu/ml. PhageAS1 was stable at a wide range of pH and temperature. The maximum stability was recorded at 37ºC and pH 7.0, while showing its normal lytic activity at temperature 60ºC and from pH 5.0 to11.0 respectively. At temperature 70ºC, phage activity was somewhat reduced whereas, further increase in temperature and decrease or increase in pH completely inactivated the phage. From the current study, it was concluded that waste water is a best source for finding bacteriophages against multi-drug resistant bacterial strains and can be used as bacterial control agent.

Suicide, self-harm and thoughts of suicide or self-harm in infectious disease epidemics: a systematic review and meta-analysis.

AIMS: Suicide accounts for 2.2% of all years of life lost worldwide. We aimed to establish whether infectious epidemics are associated with any changes in the incidence of suicide or the period prevalence of self-harm, or thoughts of suicide or self-harm, with a secondary objective of establishing the frequency of these outcomes. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO and AMED were searched from inception to 9 September 2020. Studies of infectious epidemics reporting outcomes of (a) death by suicide, (b) self-harm or (c) thoughts of suicide or self-harm were identified. A random-effects model meta-analysis for the period prevalence of thoughts of suicide or self-harm was conducted. RESULTS: In total, 1354 studies were screened with 57 meeting eligibility criteria, of which 7 described death by suicide, 9 by self-harm, and 45 thoughts of suicide or self-harm. The observation period ranged from 1910 to 2020 and included epidemics of Spanish Flu, severe acute respiratory syndrome, human monkeypox, Ebola virus disease and coronavirus disease 2019 (COVID-19). Regarding death by suicide, data with a clear longitudinal comparison group were available for only two epidemics: SARS in Hong Kong, finding an increase in suicides among the elderly, and COVID-19 in Japan, finding no change in suicides among children and adolescents. In terms of self-harm, five studies examined emergency department attendances in epidemic and non-epidemic periods, of which four found no difference and one showed a reduction during the epidemic. In studies of thoughts of suicide or self-harm, one large survey showed a substantial increase in period prevalence compared to non-epidemic periods, but smaller studies showed no difference. As a secondary objective, a meta-analysis of thoughts of suicide and self-harm found that the pooled prevalence was 8.0% overall (95% confidence interval (CI) 5.2-12.0%; 14 820 of 99 238 cases in 24 studies) over a time period of between seven days and six months. The quality assessment found 42 studies were of high quality, nine of moderate quality and six of high quality. CONCLUSIONS: There is little robust evidence on the association of infectious epidemics with suicide, self-harm and thoughts of suicide or self-harm. There was an increase in suicides among the elderly in Hong Kong during SARS and no change in suicides among young people in Japan during COVID-19, but it is unclear how far these findings may be generalised. The development of up-to-date self-harm and suicide statistics to monitor the effect of the current pandemic is an urgent priority.

Design, synthesis, biological evaluation, and docking studies of some novel chalcones as selective COX-2 inhibitors.

A new series of chalcones (1-9) possessing an SO2 CH3 COX-2 pharmacophore at the para position of the C-1 phenyl ring was synthesized via the Claisen-Schmidt condensation reaction and examined for their inhibition potential against cyclooxygenase (COX) enzymes. Their structures were elucidated by infrared, 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high-resolution mass spectroscopic methods. Enzyme inhibition studies revealed that most of the compounds showed a moderate-to-strong inhibitory activity (IC50 = 0.18-0.34 µM) against the COX-2 enzyme as compared with celecoxib (IC50 = 0.12 µM), ibuprofen (IC50 = 5.33 µM), and nimesulide (IC50 = 1.68 µM). Among these compounds, 1-[4-(methylsulfonyl)phenyl]-3-(2,3-dichlorophenyl)prop-2-en-1-one (5), 1-[4-(methylsulfonyl)phenyl]-3-(2,4-dichlorophenyl)prop-2-en-1-one (6), and 1-[4-(methylsulfonyl)phenyl]-3-(2-chloro-6-fluorophenyl)prop-2-en-1-one (8) became prominent with IC50 values of 0.21, 0.19, and 0.18 µM, respectively. According to molecular docking studies of the most effective compounds, it was found that the compounds interact with amino acids that are important in COX-2 selectivity, such as Arg499 and Phe504.

The Additive Effects of Midazolam in Sub Arachnoid Block in Elective Caesarian Section: A Randomized Control Trial.

The incidence of visceral pain among caesarean section can be as high as 50% in sub arachnoid block (SAB) in spite adequate sensory block, which requires conversion to general anesthesia. Different types of adjuvant have been used to augment the effect of local anesthetics but their use is limited due to adverse effects. The effect of intrathecal midazolam along with hyperbaric bupivacaine in sub arachnoid block is less known. So this randomized, double blind study was conducted to evaluate the additive effect of 0.4ml midazolam to 0.5% 3ml bupivacaine on sub arachnoid block in scheduled elective caesarean section. This study demonstrated that the addition of intrathecal 0.4ml midazolam to spinal 0.5% bupivacaine kept all the characteristics of block unaffected, furthermore pain score VAS 3.4±1.3 in Group A and 1.8±1.22 in Group B which is statistically significant, the requirement of intraoperative analgesia and also increased the duration of postoperative analgesia that is 130.3±5.4 minute in Group A, 265.1±3.6 minute in Group B and also statistically significant. Therefore addition of 2.0mg midazolam with 0.5% bupivacaine significantly reduces the VAS score, reduces the intraoperative visceral pain and need of analgesia.

Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors.

Aromatase is involved in the biosynthesis of estrogen and thus is a critical target for breast cancer. In this study, to identify new aromatase enzyme inhibitors, seven 3-[4-(5-methyl-1H-benzo[d]imidazol-2-yl)phenyl]-6-(substituted phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives were synthesized. First, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the inhibitory activity of the synthesized compounds on the MCF-7 cell line. The aromatase inhibitory activity was determined for the active compounds 5b, 5c, 5e, and 5g on the MCF-7 cell line. Compound 5g showed significant aromatase inhibitory activity (IC50 = 0.037 ± 0.001 µM). Interestingly, this compound, which bears a difluoro substituent at positions 2 and 4 of the phenyl ring, displayed the most potent aromatase inhibitory activity without significant cytotoxicity to a normal healthy cell line (NIH3T3). Furthermore, the interactions between the best active compounds and the active site of the enzyme were analyzed through a docking study. The results of this study determined that benzimidazole-triazolothiadiazine derivatives are promising compounds that should be further developed as a novel class of aromatase inhibitors.

Deformation analysis of suspended type cut off wall of diversion structures.

Numerical study is carried out to analyse the behaviour of cut off walls in sandy soil, under constant differential pressure head, by varying its location from upstream end to downstream end. The deformation and bending moment in cut off wall are at their lowest magnitude when the cut off wall is positioned at upstream end. The cut off wall is subjected to second lowest deformation, when it is positioned at downstream end. The maximum deformation occurs, when the cut off wall is positioned at 0.60 times the total width of diversion dam from upstream end. The seepage rate in the diversion dam is highest when the cut off wall is positioned at centre of the diversion dam. The seepage rate in the diversion dam is having direct relation with the maximum displacement and maximum bending moment. The seepage force found to be more predominant than the pressure gradient and active pore pressure variations in deforming the cut off walls of diversion dams.