Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum concentrations of tumour necrosis factor‐alpha (TNF‐α) and soluble TNF‐α receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function

backgbound Tumour necrosis factor‐α (TNF‐α) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF‐α have been demonstrated in thyroid follicular cells and TNF‐α and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves’ disease, serum levels of TNF‐α have been reported to be elevated and administration of TNF‐α to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome.
Blood–brain barrier models: in vitro to in vivo translation in preclinical development of CNS-targeting biotherapeutics

Introduction: The majority of therapeutics, small molecule or biologics, developed for the CNS do not penetrate the blood–brain barrier (BBB) sufficiently to induce pharmacologically meaningful effects on CNS targets. To improve the efficiency of CNS drug discovery, several in vitro models of the BBB have been used to aid early selection of molecules with CNS exposure potential. However, correlative studies suggest relatively poor predictability of in vitro BBB models underscoring the need to combine in vitro and in vivo BBB penetration assessment into an integrated preclinical workflow. Areas covered: This review gives a brief general overview of in vitro and in vivo BBB models used in the pre-clinical evaluation of CNS-targeting drugs, with particular focus on the recent progress in developing humanized models. The authors discuss the advantages, limitations, in vitro–in vivo correlation, and integration of these models into CNS drug discovery and development with the aim of improving translation. Expert opinion: Often, a simplistic rationalization of the CNS drug discovery and development process overlooks or even ignores the need for an early and predictive assessment of the BBB permeability. Indeed, past failures of CNS candidates in clinical trials argue strongly that the early deployment of in vitro and in vivo models for assessing BBB permeability, mechanisms of transport and brain exposure of leads, and the co-development of BBB delivery strategies will improve translation and increase the clinical success of CNS pipelines.
The Effects On and Of Depression - An Exploratory Study of Rehabilitation and Secondary Prevention in Coronary Artery Disease

Forty consecutive participants in a comprehensive, behaviourally oriented coronary rehabilitation and secondary prevention program were followed for three years. Changes in depression (as measured with the Beck Depression Inventory) as well as the influence of baseline levels of depression on achieved changes in lifestyle behaviour and on rehabilitation and secondary prevention effects were analyzed. Subjects with moderate levels of baseline depression experienced short-term reductions of depression, which was maintained at the 12-month follow-up. Clinically depressed subjects experienced less positive results, with smaller immediate reductions as well as relapse to baseline levels after 12 months, specifically in non-physical, cognitive-affective depression symptoms. There were, however, no differences in lifestyle changes or in hospital treatment between groups with different pre-treatment depression levels. These results are discussed in relation to earlier research on the detrimental effects of depres.
Thalidomide: Still an important second-line treatment in refractory cutaneous lupus erythematosus?

Abstract Background: Cutaneous lupus erythematosus (CLE) can be a severe disease, characterized by extensive, disfiguring lesions and a relapsing course. Thalidomide is known as an effective treatment for CLE, however, its use is restricted by its potential side-effects. Nevertheless, it remains a valuable option to consider. Therefore, it is important to report new clinical experiences. Methods: The data of 30 patients with refractory CLE, who were treated with thalidomide, were retrospectively analyzed. The response rate was categorized as complete, partial or no response. The relapse rate and the occurrence of side-effects were registered. Results: Six patients prematurely discontinued treatment because of side-effects. The response rate was 100% in the remaining 24 patients, including 20 patients (83%) with complete response and 4 (27%) with partial response. Clinical relapse was frequent (73%) and occurred between 3 and 24 weeks after withdrawal of thalidomide. Nine patients (30%) developed peripheral neuropathy. In the majority, there was no complete resolution of the neuropathy-associated symptoms after stopping thalidomide. One patient developed a thrombosis in an artery stent. Conclusion: Because of high risk of polyneuropathy, low-dose thalidomide should be used and long-term therapy should be avoided. Therefore, it should be recommended to combine thalidomide with other treatments for CLE.
Preparation and evaluation of chitosan microspheres containing nicorandil

Objectives: The objective of present study was to develop chitosan-based sustained release nicorandil microspheres to reduce the dosing frequency. Materials and Methods: The nicorandil-loaded chitosan microspheres were formulated by emulsion crosslinking method. A 32 factorial design was employed to study the influence of drug: Polymer ratio and volume of glutaraldehyde (GA) on percentage entrapment efficiency, particle size, and % drug release at 8 h. Results: The entrapment efficiency was found to be 41.67 ± 1.43-77.33 ± 1.97% and particle size range 65.67 ± 2.08-146.67 ± 2.18 μm. The batch CH5 showed 79.11 ± 2.23 and 96.21 ± 2.41% drug release at 8 and 12 h, respectively. Conclusions: Drug: Polymer ratio and volume of GA had significant effect on % entrapment efficiency, particle size, and % drug release. From the scanning electron microscopy (SEM) study observed that microspheres were spherical and fairly smooth surface. Fickian diffusion was the mode of drug release from nicorandil-loaded chitosan microspheres formulations.
Design and optimization of bilayered tablet of Hydrochlorothiazide using the Quality-by-Design approach

Aim: The aim of the present study is to develop an optimize bilayered tablet using Hydrochlorothiazide (HCTZ) as a model drug candidate using quality by design (QbD) approach. Introduction and Method: The bilayered tablet gives biphasic drug release through loading dose; prepared using croscarmellose sodium a superdisintegrant and maintenance dose using several viscosity grades of hydrophilic polymers. The fundamental principle of QbD is to demonstrate understanding and control of pharmaceutical processes so as to deliver high quality pharmaceutical products with wide opportunities for continuous improvement. Risk assessment was carried out and subsequently 22 factorial designs in duplicate was selected to carry out design of experimentation (DOE) for evaluating the interactions and effects of the design factors on critical quality attribute. The design space was obtained by applying DOE and multivariate analysis, so as to ensure desired disintegration time (DT) and drug release is achieved. Bilayered tablet were evaluated for hardness, thickness, friability, drug content uniformity and in vitro drug dissolution. Result: Optimized formulation obtained from the design space exhibits DT of around 70 s, while DR T95% (time required to release 95% of the drug) was about 720 min. Kinetic studies of formulations revealed that erosion is the predominant mechanism for drug release. Conclusion: From the obtained results; it was concluded that independent variables have a significant effect over the dependent responses, which can be deduced from half normal plots, pareto charts and surface response graphs. The predicted values matched well with the experimental values and the result demonstrates the feasibility of the design model in the development and optimization of HCTZ bilayered tablet.
Post-translational modification of heat-shock protein 90: impact on chaperone function

Heat-shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of many signaling proteins that are often activated, mutated or overexpressed in cancer cells and that underly cancer cell proliferation and survival. Hsp90 is a conformationally flexible protein that associates with a distinct set of cochaperones depending on ATP or ADP occupancy of an N-terminal binding pocket. Nucleotide exchange and ATP hydrolysis by Hsp90 itself, with the assistance of cochaperones, drive the Hsp90 chaperone machine to bind, chaperone and release client proteins. Cycling of the Hsp90 chaperone machine is critical to its function. Although ATP binding and hydrolysis have been convincingly implicated in regulating the Hsp90 cycle, growing evidence suggests that various post-translational modifications of Hsp90, including phosphorylation, acetylation and other modifications, provide an additional overlapping or parallel level of regulation. A more complete understanding of how these various protein modifications are regulated and interact with each other at the cellular level to modulate Hsp90 chaperone activity is critical to the design of novel approaches to inhibit this medically important molecular target.
Eliciting the Views of Children About Health in Schools Through the Use of the Draw and Write Technique

SUMMARY A draw and write scenario was devised in order to elicit the views of primary school pupils (ages 8‐12) regarding the qualities they would expect to see in a school which promotes health, and the qualities their own schools need to develop to become more health promoting. The draw and write investigation was conducted in a sample of six primary schools in Lothian, Scotland. These schools are located in both urban and rural environments, and cater for communities of different socioeconomic status. Categorisation of the children’s responses revealed that the majority of pupils from all the schools considered issues relating to healthy eating, the school environment and exercise as being vital elements of a healthy school. There was inter-school variation in the richness of data produced and range of responses given. The scenario was also capable of detecting intra-school similarities and differences in response. We conclude that this draw and write investigation could be utilised to ascertain pupils’ opinions on the qualities schools need to possess and develop to promote health. These views, in turn, could help to inform the development of the Health Promoting School concept.
Assessment of drug-drug interactions in hypertensive patients at a superspeciality hospital

Abstract Objective: The objective of the study was to assess the incidence and pattern of drug-drug interactions (DDIs) in hypertensive patients by using Micromedex and Medscape databases. Materials and Methods: A prospective observational study was carried out in a superspeciality hospital setting in South India for period of 9 months. Hypertensive patients who admitted into the hospital with the age more than 18 years, received more than 3 drugs per prescription and length of hospital stay for more than 24 hours were included in the study. An appropriate data was collected and assessed for DDIs with the help of Micromedex and Medscape databases. Results: A total of 227 patients were enrolled during the study period. Among the 227 patients, 48 of them developed 53 clinically significant DDIs. Out of 48 patients, most of them were in the age-group of 50-60 years [18 (37.49%)]. The percentage of DDIs were higher in males [30 (62.5%)] compared to females [18 (37.5%)]. The most common drugs responsible for DDIs in the present study were Insulin [18 (33.96%)] followed by Metoprolol [10 (18.86%)], Torsemide [8 (15.09%)], and Hydrochlorothiazide [8 (15.09%)]. The most commonly interacting pairs were Ciprofloxacin-Insulin [6 (11.32%)], followed by Metoprolol-Insulin [4 (7.54%)] and Atenolol-Insulin [4 (7.54%)]. The most common consequences of interacting pairs were reduced serum potassium levels and hyperglycemia. Conclusion: The overall incidence rate of DDIs was found to be 21.14% and the increasing number of co-morbidities ( P ≤ 0.003) and polypharmacy ( P ≤ 0.002) were the risk factor for the development of significant number of DDIs.
Socio-Economic Dependence on the Incidence of Tuberculosis in Jos, North Central Nigeria

Background: Mycobacterium tuberculosis remains a disease of serious public health concern due to its high tendency of person-person transmission, morbidity, and mortality. Objective: This study aimed at determining the prevalence of AFB in relation to some socioeconomic variables within the study area. Methods: Sputum samples were collected from three hundred and three (303) patients with suspected cases of pulmonary tuberculosis in Jos, Nigeria. The samples were examined using Ziehl Neelsen method. Structured questionnaires were administered to obtain some demographic data from patients that consented. Results were tested statistically for significance at p 0.05). Income status of individuals showed a significant effect on the prevalence (p < 0.05). Conclusion: Pulmonary tuberculosis was recorded more among patients with low socio-economic status. There is need for a more collaborative efforts and political will by the government and non-governmental agencies in order to eliminate the infection in the nearest future.
Natural products derived from plants as a source of drugs

10.4103/2231-4040.104709 Nature, the master of craftsman of molecules created almost an inexhaustible array of molecular entities. It stands as an infinite resource for drug development, novel chemotypes and pharmacophores, and scaffolds for amplification into efficacious drugs for a multitude of disease indications and other valuable bioactive agents. Since time immemorial, natural products have been the backbone of traditional system of healing throughout the globe, and have also been an integral part of history and culture. Although the use of bioactive natural products as herbal drug preparations dates back hundreds, even thousands, of years ago, their application as isolated and characterized compounds to modern drug discovery and development started only in the 19th century. It has been well documented that natural products played critical roles in modern drug development, especially for antibacterial and antitumor agents. Even though popularity of the synthetic products increased due to its production cost, time effectiveness, easy quality control, stringent regulation and quick effects, but their safety and efficacy was always remained questionable, resulting in the dependence on the natural products by more than 80% of the total population in the developing world, because of its time tested safety and efficacy. A huge number of natural product-derived compounds in various stages of clinical development highlighted the existing viability and significance of the use of natural products as sources of new drug candidates.
Will in vitro maturation ever be used in all IVF patients

In vitro maturation of human oocytes obtained from unstimulated ovaries offers a more ‘patient friendly’ treatment option than conventional IVF treatment with ovarian stimulation to the couples undergoing assisted reproductive technologies. It has classically been offered to women who are considered high risk for ovarian hyperstimulation syndrome. Since significant progress has been made to improve the implantation and pregnancy rates using in vitro matured oocytes, the patient spectrum for in vitro maturation treatment has become wider. However, implantation and pregnancy rates of conventional IVF are still higher than those of unstimulated cycles followed by in vitro maturation. To improve the in vitro maturation outcomes, some studies have focused on improving in vitro culture conditions, whereas others have tried to improve the quality and quantity of oocytes retrieved by modifications in the follow-up of treatment cycles.
The potential for cancer combination therapy with multi-targeted, single-protein pharmaceuticals

Many diseases and disorders are best treated by a combination of drugs. Unlike small molecules, engineered proteins can be designed to incorporate multiple independent drug activities. Compared with a combination of two or more proteins, the potential benefits of a single biologic that inhibits multiple targets may include lower cost, simplified clinical testing and greater patient convenience. The evolution of HIV combination therapy is a useful point of comparison, as it occurred in an unusual regulatory environment that allowed the testing of combinations when the clinical benefit of component drugs was unproven. The epidermal growth factor receptor family of cancer targets illustrates how a particular single-molecule combination therapy might be used for cancer therapy, so some attempts to construct single-protein agents with multiple activities that include anti-EGFR moieties are reviewed. Protein engineers have created an armory of multiply-targeted antibody derivatives, but such engineered molecules often have a shorter serum half-life than IgG antibodies. New protein engineering approaches may be needed to address this problem. Nonetheless, multiply-targeted single-protein agents may be an economical solution to the problem of antibody combination therapy for cancer.
Determination of the Level of Emergency Medicine Resident Physicians to Recognize the Electrocardiography Findings

Objective: The aim of this study is to determine the accuracy and reliability of the interpretation of electrocardiography (ECG) findings by emergency medicine resident physicians (EMPs) and to provide training recommendations in line with emerging deficiencies. Material and Methods: This research depended on the data from a questionnaire that we conducted among EMPs in Ankara. The survey included multiple-choice questions, selected through conceived cases presented in major textbooks or congresses. EMP ECG assessment levels were compared according to the duration of residency education and the presence of ECG education. The data were evaluated by using the Statistical Package for Social Sciences 17.0 (SPSS Inc., Chicago, IL, USA). Results: A total of 112 volunteers participated. Mean age was 29.6±4.4; also, 47 were female and 65 were male. When all of the questions were taken into account, the mean number of total correct answers was higher for those who had received ECG training than who had not received it, those who underwent more training than those who underwent less training, and those whose duration of assistantship was longer than those whose duration was shorter. Conclusion: The results of our study revealed that the evaluation of ECG is improved by increasing clinical knowledge and training. Depending on these results, we suggest that effective and practical ECG courses and training programs should be organized for EMPs. (JAEM 2014; 13: 108-11)
Smoking during pregnancy in the 1990s.

Objectives—This report presents trends and variations in smoking during pregnancy in the United States. Data are presented for various characteristics including mother’s age, race, ethnic origin, place of birth and State of residence, live birth order, and birthweight. Methods—Descriptive tabulations of data reported on the birth certificates are presented. Results—The percentage of women who smoked during preg­ nancy declined every year from 1990 through 1999. In 1999, 12.3 percent of women giving birth reported smoking during pregnancy. For women 15 to 19 years of age, the rate of smoking during pregnancy declined between 1990 and 1994 but has increased since then and teenagers now have the highest rate of all age groups. Maternal smoking rates also declined for all race and ethnic groups in the 1990s, but important differences persist. American Indian, non-Hispanic white, and Hawaiian women had the highest rates of smoking during preg­ nancy in 1999 while, Chinese and Central and South American women had the lowest smoking rates.
Surf Lifeguard Perceptions and Practice of Cardiopulmonary Resuscitation (CPR)

While the importance of lifeguards in providing immediate and effective basic life support (BLS) in drowning has been well reported, not a lot is known about how lifeguards perceive the relative value of CPR as a lifeguard skill, their training in it, and the likelihood of resuscitation being successful. A self-complete questionnaire was done by 252 volunteer surf lifeguards at 16 surf beaches in the Greater Auckland NZ region. Results show that most lifeguards (65%) had received training in the 3 months before the survey, 83% were willing to perform CPR, few (9%) had used CPR in an emergency, and many had a realistic expectation of the likelihood of CPR being successful. Recall of CPR compression rates (86%) was very good but initial steps at an emergency scene were less accurately recalled. Ways to address the misconceptions reported in the survey through enhanced training programs are discussed.
Unusual variation in musculocutaneous nerves

Background: Variations in origin, course, branching pattern, termination and connections of the musculocutaneous nerve in the arm are not as uncommon as was once thought. Variational study of nerve in Nepalese is very less and can be of surigical-clinical importance. This opinion led us to performing this study. Objectives: The aim of this study was to a study in Nepalese which could be important for clinical investigation and the surgical treatment of peripheral nerve injury. Materials and methods: This study was carried out in Manipal College of medical sciences (MCOMS). Dissection of formalised 16 cadavers (n=32 upper limbs) were carried out using normal dissection kit with the help of standard dissection manual in two and half years. Results: The study revealed the variation in course, branching pattern and termination of musculocutaneous nerve in 6.25% of cases unilaterally on the right side. No statistically significant differences by gender and side were observed. Conclusion: This present study provides the evidence of variation of musculocutaneous nerve in Nepalese. The knowledge of the anatomical variations of the peripheral nerve system can help explain an incomprehensible clinical sign. Key words: Musculocutaneous nerve; Median nerve; Brachial plexus; Peripheral nerve repair. DOI: 10.3126/kumj.v7i4. 2763 Kathmandu University Medical Journal (2009) Vol.7, No.4 Issue 28, 408-410
Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells

Background: It has been shown that plants from the family Rhamnaceae possess anticancer activity. In this study, we sought to determine if Ziziphus spina-christi, a species from this family, has cytotoxic effect on cancer cell lines. Materials and Methods: Using maceration method, different extracts of leaves of Z. spina-christi were prepared. Hexane, chloroform, chloroform-methanol (9:1), methanol-water (7:1) methanol, butanol and water were used for extraction, after preliminary phytochemical analyses were done. The cytotoxic activity of the extracts against Hela and MDA-MB-468 tumor cells was evaluated by MTT assay. Briefly, cells were seeded in microplates and different concentrations of extracts were added. After incubation of cells for 72 h, their viability was evaluated by addition of tetrazolium salt solution. After 3 h medium was aspirated, dimethyl sulfoxide was added and absorbance was determined at 540 nm with an ELISA plate reader. Extracts were considered cytotoxic when more than 50% reduction on cell survival was observed. Results: Hexane, chloroform, chloroform-methanol, butanol, methanol-water and aqueous extracts of Z. spina-christi significantly and concentration-dependently reduced viability of Hela and MAD-MB-468 cells. In the both cell lines, chloroform-methanol extract of Z. spina-christi was more potent than the other extracts. Results: From the finding of this study it can be concluded that Z. spina-christi is a good candidate for further study for new cytotoxic agents.