Calorie Restriction Effect on Circadian Clock Gene Expression

Calorie Restriction (CR) is a powerful paradigm known to delay aging and thus increase longevity in several organisms, from yeast to non-human primates. Many molecular pathways have been proposed to mediate the beneficial effects of CR, however, the mechanism is still unknown. Circadian clock which is an internal time keeping system is regulated by feeding. Thus our aim was to study the effect of CR on the circadian clock. Here we show that CR significantly affects the expression of circadian clock genes in mice at the mRNA and protein levels, suggesting that CR reprograms the clocks at the transcriptional and post-transcriptional level. CR also affected the circadian output through up- or down-regulation of the expression of several clock-controlled transcriptional factors and the longevity candidate genes. CR-dependent effects on some clock gene expression were impaired in the liver of mice deficient for BMAL1, suggesting importance of this transcriptional factor for the transcriptional reprogramming of the clock, however, BMAL1-independent mechanisms exist too. We have shown that Bmal1 deficient mice develop premature aging phenotype and have a shortened lifespan. We decided to apply 30%CR to these mice and found that CR did not increase the lifespan of these Bmal1 mutants, further suggesting that BMAL1 is necessary for full benefits of CR. We also analyzed the plasma levels of IGF-1 and insulin, which were found to be impaired in Bmal1 deficient mice on 30%CR. We propose that CR recruits biological clocks as a natural mechanism of metabolic optimization and synchronization of the several downstream pathways under limited nutrient conditions

Analysis of CFT, RCC and Steel Building Subjected to Lateral Loading

AbstractSteel–concrete composite columns are used extensively in modern buildings. Extensive research on composite columns in which structural steel section are encased in concrete have been carried out. In-filled composite columns, however have received limited attention compared to encased columns. In this paper a comparative study of 10, 20 and 30 storey Concrete Filled Steel Tube (CFT), R.C.C. and Steel building is done. Comparison of parameters like time period, displacement, base shear and load carrying capacity is done with steel and R.C.C structures. Result shows CFT building is good in load carrying capacity with small cross section of column

The design and evaluation of targeted patient-centred health information to improve knowledge and behavioural outcomes in tuberculosis patients with limited literacy

South Africa carries a significant TB burden as evidenced in the 2013 statistics which report 450 000 new active TB cases and 890 000 TB-related mortalities. For successful treatment outcomes, 90% adherence is necessary, but many patients prematurely discontinue treatment due to poor knowledge and understanding of their complex TB medicines. Patient education is pivotal in improving knowledge, health literacy and behavioural outcomes such as health information seeking, self-efficacy and adherence. In the under-resourced South African healthcare system, time and capacity to adequately counsel patients are limited. The value of written medicine information (WMI) to supplement the verbal information provided by healthcare professionals (HCPs) has been widely investigated but minimal South African research is available. Current WMI distributed in South Africa is mainly generated by pharmaceutical manufacturers and is complex, incomprehensible and undesirable to patients. TB-related WMI focuses mainly on the disease, with little information relating to TB medicines and their use. The overall aim of this project was to improve patient knowledge about their TB medicines through the use of a simple illustrated patient information leaflet (PIL). Objectives to achieve this aim included: investigation of the medicine information seeking behaviour (MISB) of long term patients attending public health sector facilities; the development and validation of a medicine literacy test (MLT) to identify patients with limited health literacy requiring additional support and counselling; the development and evaluation of a patient-centred illustrated PIL for first-line TB treatment; the assessment of self-efficacy and adherence using modified versions of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and Morisky 8-item Medicine Adherence Scale (MMAS-8), respectively, and the investigation of the impact of the PIL on patient knowledge and these health-related behaviours. Six focus group discussions (FGDs) conducted in 34 isiXhosa-speaking patients with limited formal education taking long-term treatment explored themes related to information needs, information-seeking practices and awareness of and ability to utilize information sources. Codes were analysed and potential themes and subthemes were identified and refined. The findings of this study reflected a passive, disempowered patient due to both patient-related and systemic healthcare factors. Poor awareness of information sources, lack of health-related knowledge, stigma and lack of awareness of the importance of appropriate medicine-related knowledge contributed to a lack of information-seeking practice. Patients neither asked questions nor were encouraged to do so. All expressed an unmet need for information and a desire for receiving relevant, appropriate, written medicine-related information. Feedback from this phase of the study was used to inform the development of the targeted patientcentred PIL. A double-sided A4 PIL containing information about TB medicines was designed giving careful consideration to content, format and layout features. Twenty five pictograms were designed through a rigorous, iterative design process and were included in the PIL that was evaluated in a randomised control trial (RCT) conducted amongst 120 TB patients attending a high burden TB clinic in South Africa. Interviews were conducted in either isiXhosa or Afrikaans via a trained interpreter. Patients were randomly allocated to either a control (standard care) or an experimental group (standard care plus brief counselling using the PIL). Two interviews were conducted using a prepared questionnaire; one at baseline followed by a 4-week follow-up. Baseline data included demographics, medicine literacy test, health information sources, knowledge of TB medicines, self-reported adherence and self-efficacy. Data collected at the 4-week follow-up interview included TB knowledge, self-reported adherence, self-efficacy, opinion of TB medicine information and interpretation of pictograms. Data were analysed using t-test, correlations, chi-square and ANOVA tests at a 0.05 level of significance. The PIL was successful in improving patient knowledge of the disease, TB medicine-taking, side effects, drug-resistant TB and HIV and TB co-infection. At baseline, there was no significant difference in the overall mean percentage knowledge score between the control and experimental groups (p=0.074). At follow-up, the percentage knowledge score for the experimental group increased significantly from 59.0% to 84.6% (p<0.001) and showed a significantly higher score than the control group (p<0.001), displaying evidence of the impact of the PIL as a counselling tool on patient knowledge. The PIL generated a highly positive response in the experimental group who indicated that they had referred to the leaflet over the last month and that it had played an important role in improving their TB medicine-related knowledge. This was reflected in the experimental group knowledge score of greater than 80% for almost three quarters of the patients whereas only 14% in the control group achieved this score. Patients appreciated the inclusion of pictograms and strongly felt that they helped them to recall and understand the textual PIL content. The study found that patients want side effect information and, interestingly, did not perceive the presentation of side effects in pictorial form to constitute a risk factor for nonadherence. Use of the illustrated PIL (experimental group) resulted in a significant improvement in patient self-efficacy (p=0.002), but showed no effect on self-reported adherence (p=0.563). Neither self-efficacy nor adherence was influenced by gender, age or education. An education effect on knowledge was only observed in the control group at baseline. The newly developed MLT was shown to be a valid and reliable tool and a moderate, positive and significant correlation was noted between the MLT score and baseline TB medicine-related knowledge in both the control and experimental groups. As there is a paucity of studies investigating the influence of take-home written leaflets on TB medicine knowledge and on patient behaviour, this study represents a significant knowledge contribution. It is the first study to report the development and evaluation of a patient-centred PIL to address the dearth of available TB medicine information. The use of targeted user-friendly, illustrated information leaflets can be a valuable counselling aid to improve patient knowledge and self-efficacy, particularly among patients with limited literacy. However, careful consideration of the design and content, with input from the endusers at all stages of the process, will optimise its effectiveness. The proposed framework for the development and implementation of patient-centred health and medicines information in a developing country context presented in this thesis could be used as a theoretical basis for informing the development of effective information materials targeting other disease states. Local patients taking TB medicines identified nurses, WMI and media as their current sources of information but they expressed a strong desire to know more about their treatment. Targeted public health interventions that focus on medicine-taking information and behaviours and encourage patients to adopt a more active, questioning role in health consultations could improve health literacy and empower patients in their medicine-taking practices.Thesis (PhD) -- Faculty of Pharmacy, Pharmacy, 201

A rare case of cervical agenesis with agenesis of the upper 2/3rd vagina with hematometra

Cervical agenesis is an extremely rare form of congenital Mullerian anomaly. Due to the rarity of the cases with different presentations ranging from cervical agenesis to dysgenesis (fragmentation, fibrous cord, obstruction of external os), along with the functionality of the uterus, there are numerous conservative surgical options involving uterovaginal anastomosis, cervical reconstruction, and cervical canalization, and total hysterectomy in cases where conservative surgical procedures fail or not feasible. In our case, the patient was a 32-year-old female with primary amenorrhea with, a history of marriage for 6 years and a history of surgery for primary amenorrhea during adolescence. During the present visit, she had severe abdominal pain due to massive hematometra with a short blind vagina. She was planned for laparoscopic Uterovaginal anastomosis but converted to abdominal hysterectomy due to the large size of uterus, lack of uterine supports, and high length of the defect between the lower end of the uterus and vaginal end. Due to the lack of proper guidelines and variations in clinical presentation, a case-based approach is required

Uterine preservation with Cho suture in localized multifocal atonicity of uterus with failed medical management and uterine tamponade

Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality, and one of the common obstetrical emergencies. Quite commonly, it occurs in patients where PPH is not expected. Management has to be swift and precise according to the steps and the response initiated by the uterine musculature during the management. In our patient, we had a localized multifocal atony of the uterus, at points where the uterine sinuses were bleeding due to atony, and medical management and uterine tamponade failed, with a raised D-dimer level. As the stepwise management failed with uterine devascularisation failing to control PPH, a decision for uterine compression suture (UCS), Cho suture was taken

Effect of Phyllostachys parvifolia leaf extract on ionizing radiation-induced genetic damage: A preliminary in vitro cytogenetic study

AbstractThe ionizing radiation is a known carcinogen as well as cancer therapeutic agent however, the side effect on normal tissue is a limiting factor and inadequate doses necessitates search for an ideal radioprotective agent. Bamboo species are rich source of antioxidants hence have therapeutic value in many free radical mediated diseases. This is the first report regarding in vitro protective effect of bamboo leaf extract against radiation induced genetic damage in human peripheral blood lymphocytes by cytokinesis blocked micronuclei (CBMN) assay. Fresh whole blood was exposed to 5Gy of cobalt-6o gamma radiation with or without 30 min pre-treatment with 3 μl and 5 μl of hydro alcoholic leaf extract of Phyllostachys parvifolia. In addition to whole extract the effect of potential active compound orientin was also assessed. The frequency of radiation induced micronuclei decreased significantly in a dose dependent manner following treatment with whole extract as well as orientin. The extent of reduction in micronuclei frequency was higher with whole bamboo leaf extract as compared to orientin alone

Thermal Analysis of the Molten Lead Kettle Failure at the Galvanizing Plant and Development of Novel Design Using CFD Techniques

ABSTRACT: The present work discusses problem of failure of kettle holding molten lead in a galvanizing plant. A CFD code Fluent was used to solve the problem using computational approach. The geometry is built in the GAMBIT environment and 3D solvers for turbulence, combustion and radiation heat transfer was applied. The study revealed the detection of the hot spot exactly at the same location of the kettle that was observed at the plant. This confirms the validity of the CFD Model. Based on this model the suggestions are made to overcome kettle bulging. For this two approaches are suggested. They are, differential heating of the kettle and the reduction in the width of the burner. The effect of both these alternatives is studied using a CFD model and the effectiveness of the results are discussed and compared using dimensionless surface parameter representing the temperature distribution and flue gas temperature. Based on the results obtained an improvised geometry for the kettle heating is proposed. The proposed novel design has the following features: 50% reduction in the fuel consumption and lower start-up time. Separation of the zone of mechanical and thermal stresses and lower concentration of thermal stresses. Increase in the heat transfer area and a reduction in the heat losses through the exhaust. Reduction in the amount of lead used for the operation

Risk Factors and Protective Factors for COVID-19 Infection among Patients Visiting University Health Centre of Vadodara District: A Case Control study

Introduction: Identification of risk factors and protective factors of COVID-19 can help in controlling the disease in healthcare and the community. Objective: To determine the risk factors and protective factors of COVID-19 among patients visiting University Health Centre of Vadodara district. Method: A case control study was done at University Health Centre of the district. Hundred cases who were COVID-19 positive by RTPCR/RAT testing and 100 controls who were RTPCR/RAT negative and never displayed its signs and symptoms were asked about knowledge of parameters such as hand hygiene, social distancing, any ayurvedic or homeopathic medicine intake, chemoprophylaxis of HCQ, visit to public places, any travel history outside city, state or country, the manner, place, and type of masks used by them to know the risk and protective factors for COVID-19. Results: Significant risk factors for COVID-19 infection based on logistic regression were increasing age (OR=3.65, p=0.004), higher education (OR=4.72, p=0.001), self-medication of homeopathic or ayurvedic medicines (OR=6.27, p=0.005). Significant protective factors for COVID-19 infection based on logistic regression were regular use of mask (OR=0.03, p=<0.0001), correct technique of mask use (OR=0.17, p=0.02), and maintaining social distance (OR=0.18, p=0.049). Conclusion: This study revealed the factors associated with occurrence of COVID-19 were increasing age, higher education, self- medication and factors which protect from infection were regular use of mask, correct technique of mask use, and maintaining social distance