In silico identification of potential inhibitors for human aurora kinase b

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer

Amniotic band syndrome at 14 weeks of gestation: a case report and literature review

Amniotic band syndrome comprises of a group of congenital anomalies involving the limbs, trunk, head and face characterised by asymmetry of involvement and varying severity. While mild variants have a good prognosis with normal life expectancy, severe cases may be incompatible with life. It is sporadic in occurrence with many theories postulated towards the pathogenesis. We report a case of amniotic band syndrome diagnosed at 14 weeks gestation in a 22 year old low risk primigravida-the foetus was seen as an amorphous mass with multiple anomalies, confirmed by autopsy. While early ultrasound helped detect lethal anomalies, correlation with autopsy provided an insight into possible disruptions in early foetal development leading to the various anomalies

Effectiveness of structured teaching programme on cancer cervix among women who are attending OPD in Melmaruvathur Adhiparasakthi institute of medical sciences and research

EFFECTIVENESS OF STRUCTURED TEACHING PROGRAMME ON CANCER CERVIX AMONG WOMEN WHO ARE ATTENDING OPD IN MELMARUVATHUR ADHIPARASAKTHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH. OBJECTIVES 1. To assess the level of knowledge of women regarding cancer cervix. 2. To evaluate the effectiveness of teaching programme on cancer cervix among women. 3. To determine the association between the effectiveness of teaching programme on cancer cervix with the selected demographic variables. OPERATIONAL DEFINITIONS Effectiveness It refers to the extent to which the structured teaching programme in women regarding cancer cervix has achieved the effect in improving the knowledge, attitude of women. Structured teaching programme It refers to the information gained by women regarding cancer cervix as measured by structured questionnaire. Women Women in the age group of 30 to 55 years. Cancer cervix An abnormal growth of cancer cells present in the neck of the uterus. ASSUMPTIONS Women will have inadequate knowledge about cancer cervix. 1. Women need education regarding cancer cervix. 2. Structured teaching programme will enrich their knowledge regarding cancer cervix. LIMITATION OF THE STUDY 1. The study was limited to women who are willing to participate. 2. Sample size was limited to hundred women. 3. Period of study was limited to 6 weeks. PROJECTED OUTCOME Findings of the study will help to identify the knowledge of women which helps to plan the health education programme about cancer cervix and thereby to create knowledge among women regarding cancer cervix

In silico identification of potential inhibitors for human aurora kinase b

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer

An observational study on standardization of siddha diagnostic tools of Kumbavatham [Periarthritis] including line of treatment and dietary regimen

Kumbavaatham is one of the eight types of Vatha disease described by spiritual giant yugi in one of his classics yugi vaithya cintamani 800. 40 cases were analysed for the study in Arignar Anna Government hospital Arumbakkam Chennai. The sample size of 40 cases for the study on the topic Kumbavaatham is approved by IEC. Interpretation of Age: majority of the cases were under the age group of 41 – 60 years.Majority of cases under pithakaalam. (i,e) during 34-66 years. (middle age group). Interpretation of Gender: In the study population, majority of the cases affected females than males. So this study indicates that kumbavaatham is predominant in Females. Among 40 Cases, 29 cases are non diabetic and 11 cases are diabetic Interpretation of Occupation: we see 52.50% of cases were Home makers and labour work like driving or shoveling activities. Due to such orientation of work, heavy movement and in the arm kumbavaatham had occurred. And also due to diabeties patients are affected by the disease of kumbavaatham. Interpretation of Diet:Most of the cases (92.5%) were consuming mixed diet (non vegetarian) than veg diet (7.5%). As people consuming mixed diet were more common in our nation that is reflected in the study of 40 sample size. Interpretation of Udal Vanmai: In the study population majority of the patients were of Iyalbu (5%) and melivu (70%) udal vanmai. Most of the cases were from neithal nilam (25%). The single centric study reveals that due to sea shore and its adjoining area vatha diseases were more common. Interpretation of kaalam: Majority of the cases were affected during Munpani kaalam (55%) and Pinpanikaalam (12.5%) . Usually Vatha diseases will be precipitated in months from aani to karthigai. The prevalence of disease in muthuvenir and kaar kaalam is due to than nilai valarchi and vaetru nilai valarchi of vatham. Out of 40 sample size. All the cases have clinical symptoms of pain and stiffness in the hand, restricted movement of the hand, and 77.5% of cases had burning sensation of the eye.In kumbavaatham poem, yugi mentioned that vertigo, pain present in lower abdomen as one of the symptoms.Patients had such pain in the past. But during visit, patients did not suffer that pain. Pain is caused by the de arrangement of Vatha humor which imbalances the other humor. The diagnostic methodology in siddha system is unique and among them naadi plays a vital role. Out of 40 sample size, 70% of cases had Vatha pitham, 30% of the cases had pitha vaatham. This observational study reveals that most of the kumbavaatham patients showed higher vaatha pitham and pitha vaatham Naadi. In Naa, among 40 cases, 70% of cases had normal tongue, 30% of cases had coated tongue, 70% of cases had normal (pinkish) tongue and 30% had pallor tongue, 97.5 % of cases had normal taste and 2.5% had sour taste, 85% of cases had vedipu visible on their tongue and 15% of cases had normal tongue and I noticed 40% had black dots and 60% had normal tongue. IN vizhi, most of the cases had pazhuppu, 77.5% of cases had burning sensation of the eyes The study reveals that in niram, majority of the cases wheatish (65%), black (30%), and had Fair of skin present (2%). In mozhi, 87.5% of cases had sama oli (medium pitched voice). In vizhi, most of the cases had venmai venvizhi (42.5%) and 45% of cases had vellupu (pallor) present, 75.5% of cases had erichal in the eyes. In sparisam, majority of the cases had mitha veppam (80%) and tenderness (5%) present. 12.5% of cases had migu veppam in affected area. In malam, majority of the cases had manjal (yellow) coloured stool (90%) and constipation (12.5%) present. Due to derangement of vatha humor constipation results. In Neerkuri most of the cases had pale yellow (Ila manjal), no froth, clear normal enjal and manam, one of the case had colorless urine, 2 cases had yellow and 5 cases had yellow and 5% of cases had dark yellow and 2 cases had frothy urine. So most of the cases had normal color, clear, normal enjal and manam, no froth. No specific association could be made out in the study of 40 sample size from the examination of neerkuri. In neerkuri the study of the 40 sample size reveals that 31 cases had pitha vaatham; 7 cases had pitham 2 cases had indicates kabham. Initially vaatha humor deranged and the derangement of these 3 humors results in a disease. The predominant derange humor might be reflected in the neikuri. The components of vaatham manually praanan is responsible to supply O2 to all over the body, samaanam is responsible for neutralization, viyaanan is responsible for movements of all parts of the body, Abaanam is responsible for all downward movements.It is inferred from the study that praanan, samaanam, viyaanan,abaanan are affected. From the study it is inferred that the components of Pitham connected with digestion, activeness and haemopoietic activity were affected. From the study, the components of deranged kabham were tharpagam, Santhigam were affected. It is inferred from the study that in all cases of kumbavaatham, the udal thathukkal saram, seneer, oon, kozhuppu, enbu moolai, sukkilam/suronitham were affected and Mandalam and Kosam were affected. The observations study indicates that majority of the cases had the manikadai nool measurements 9 ½ finger breadth. The clinical features of kumbavaatham are closely related to periarthritis in the contemporary medicine. It was observed that almost all patients had pain and stiffness in the shoulder, restricted movement of the hand, radiating pain to the hand and burning sensation of the eyes. Modern parameter indicates the Radiological findings show narrowing of joint space. On examination, most of the cases had restricted movements of shoulder joint. Difficult to abduct the hand. CONCLUSION: The disease kumbavaatham was taken for author observations as study with reference in yugi vaithya chinthamani – 800. The study on kumbavaatham was carried out in this dissertation giving importance to the changes in uyir thathukkal and udal thakkual were assessed by siddha parameters such as ennvagai thervugyal, poriyaal arithal, pulanal airthal and vinaathal. A parallel modern diagnosis was derived through routine blood test, urine test and x-ray of shoulder. For this study 40 cases were observed clinically in the out – patient division. From this study, the following data’s concluded as, Maximum incidence of age was between 41-60 years. Among 40 cases, 11 cases had diabetes they were affected by kumbavaatham. No difference was found in level of pain and disability level between periarthritis shoulder patients with and without diabetes. In vayu, pranan, viyanan, samanam, Abanam were affected in all cases. In pitham, were affected in all cases. In kapham, tharpagram, Santhigam were affected in all cases. In mandalam, surya mandalam were affected. In kosam, praanamaya kosam, annamaya kosam were affected. The observational study reveals that in envagai thervu, Naa – 2.5% of cases had inflammation of tongue Vizhi – 77.5 % of cases had burning of eyes Naadi – Majority of cases showed vaatha pitham and pitha vaatham naadi. Neer kuri – Majority of cases showed pale yellow coloured urine. Nei kuri – Majority of cases showed Aaravam (vaatham) in nei kuri. By observation of manikadainool, high occurrence is noticed with patients yielding to 9 ½ Viralkadai. Pathogenesis of kumbavaatham was primarily due to derangement of vali which then affected Azhal, Iyyam kutram in various degrees. The symptoms of kumbavaatham may be correlated with periarthritis shoulder in modern diagnosis

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further