Miracle-dz/UniFAR-FTUs huggingface dataset:
Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

ABSTRACT In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 32 Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as Cmax, Tmax, Ke, Ka, Vd and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in Cmax (two fold, p < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.
Origin and early evolution of the vertebrates: New insights from advances in molecular biology, anatomy, and palaeontology

Recent advances in molecular biology and microanatomy have supported homologies of body parts between vertebrates and extant invertebrate chordates, thus providing insights into the body plan of the proximate ancestor of the vertebrates. For example, this ancestor probably had a relatively complex brain and a precursor of definitive neural crest. Additional insights into early vertebrate evolution have come from recent discoveries of Lower Cambrian soft body fossils of Haikouichthys and Myllokunmingia (almost certainly vertebrates, possibly related to modern lampreys) and Yunnanozoon and Haikouella (evidently stem‐group vertebrates). The earliest vertebrates had an unequivocally marine origin, probably evolved mineralised pharyngeal denticles before the dermal skeleton, and evidently utilised elastic recoil of the visceral arch skeleton for suction feeding. Moreover, the new data emphasise that the advent of definitive neural crest was supremely important for the evolutionary origin of the vertebrates. BioEssays 23:142–151, 2001. © 2001 John Wiley & Sons, Inc.
Lack of Association between the BIM Deletion Polymorphism and the Risk of Lung Cancer with and without EGFR Mutations

Introduction: The BIM deletion polymorphism in intron 2 was found in a significant percent of the Asian population. Patients with epidermal growth factor receptor (EGFR) mutant lung cancers harboring this BIM polymorphism have shorter progression free survival and overall response rates to EGFR tyrosine kinase inhibitors. However, the association between the BIM deletion polymorphism and lung cancer risk is unknown. Methods: The BIM deletion polymorphism was screened by polymerase chain reaction in 765 lung cancer cases and 942 healthy individuals. Results: Carriers possessing one allele of the BIM polymorphism were observed in 13.0% of control cases and 12.8% of lung cancer cases, similar to incidence rates reported earlier in healthy individuals. Homozygote for the BIM polymorphism was observed in four of 942 healthy controls and three of 765 lung cancer cases. The frequency of the BIM deletion polymorphism in lung cancer patients was not related to age, sex, smoking history, or family history of lung cancer. The BIM deletion polymorphism was found in 30 of 212 patients with EGFR wild type lung cancers and 16 of 120 patients with EGFR mutant lung cancers. The frequency of the BIM polymorphism is similar between cancers with wild type EGFR and mutated EGFR (p = 0.78). Conclusion: The BIM deletion polymorphism was not associated with lung cancer susceptibility. Furthermore, the BIM polymorphism is not associated with EGFR mutant lung cancer.
Placental fatty acid transport in maternal obesity

Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese–diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.
Road Traffic Collisions—Case Fatality Rate, Crash Injury Rate, and Number of Motor Vehicles: Time Trends between a Developed and Developing Country

Road traffic collisions (RTCs) are one of the most common preventable causes of death and disability worldwide. We investigated changes in numbers of motor vehicles, case fatality rate, and crash injury rate for the most present recorded year (2002) 5 and 10 years before that in the United Kingdom (UK) and Sri Lanka (SL). We also investigated environmental and individual factors impacting patients at South Birmingham Trauma Unit, UK and Colombo General Hospital, SL. We conducted a descriptive cross-sectional study (both quantitative and qualitative). Over the 10-year period, numbers of motor vehicles have risen in both countries; the crash injury remained stable in both countries. Case fatality rate (far higher) in SL has decreased, as in the UK. Three hundred and twenty-five patients took part in the survey in SL, with 83 in the UK. In the categories investigated, including patient demographics, RTC environment, visual impairment, pedestrian and driver factors, the majority of results were significantly different between the two countries. Target factors such as inadequate street lighting, visual impairment, speeding, and not wearing seatbelts at time of accident were identified, and recommendations developed as a result.
Cardioprotective effects of benazepril, an angiotensin-converting enzyme inhibitor, in an ischaemia-reperfusion model of myocardial infarction in rats

Introduction. The present study evaluated the effects of benazepril, an angiotensin-converting enzyme inhibitor on haemodynamic, biochemical, and immunohistochemical (Bax and Bcl-2 protein) indices in ischaemia and reperfusion (IR) injury. Materials and methods. Male Wistar albino rats were divided into three groups and were orally administered saline once daily (IR-sham and IR-control) or benazepril (30 mg/kg/day; IR-benazepril) for 14 days. On the 15th day, in the IR-control and IR-benazepril groups, rats were subjected to left anterior descending coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical estimation and immunohistochemistry. Results. In the IR-control group, significant ventricular dysfunctions (p<0.05 vs. IR-sham group) were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in lactate dehydrogenase activity and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, were observed. Benazepril pretreatment significantly improved mean arterial pressure (p<0.01), reduced left ventricular end-diastolic pressure (p<0.05), and improved both inotropic and lusitropic function of the heart (+LVdP/dt and — LVdP/dt) (p<0.05; p<0.01) as compared to IR-control. Furthermore, benazepril treatment significantly decreased the level of thiobarbituric acid reactive substances and restored the activity of lactate dehydrogenase towards normal value (p<0.05 vs. IR-control). Conclusion. This study demonstrates that benazepril upregulated Bcl-2 protein and decreased Bax protein expression, thus exhibiting anti-apoptotic effects. These beneficial effects of benazepril will have an important implication in the therapeutic use of benazepril in ischaemic heart disease.
Erythrocyte rheological changes in obese patients: influence of hyperinsulinism.

OBJECTIVE To investigate the rheological properties of RBC in obese subjects and the factors associated with their changes. SUBJECTS Two consecutive studies of non diabetic obese subjects. MEASUREMENTS Filtration index of RBC using the Hanss hemorheometer, RBC filterability using a cell transit time analyser and RBC aggregation measured on the Myrenne aggregometer. RESULTS In both studies an increase in the filtration index of RBC, namely a reduction in their deformability, was found. In the first study the filtration index correlated negatively with hematocrit and positively with plasma C peptide levels. In the second study RBC filterability was also studied by the cell transit time analyzer in which there is no aggregate formation. The RBC transit time was not found to be different in the obese patients and in the controls, but RBC aggregation was increased and correlated significantly with body weight and BMI. RBC aggregation worsened after four days of hypocaloric diet. CONCLUSION (1) obesity, independently of the other cardiovascular risk factors, is associated with significant changes in RBC rheology; (2) these changes are probably related for the most part to plasma factors, possibly via hyperinsulinemia, even if changes in the chemical composition of the RBC membrane are not excluded, (3) RBC aggregation worsens during the first days of a hypocaloric diet; (4) rheological changes in RBC seem to be another component of the insulin resistance syndrome.
Predicting the severity of radiation skin reactions in women with breast cancer.

PURPOSE/OBJECTIVES To develop a method of predicting the severity of acute radiation skin reactions. DESIGN Prospective, descriptive correlational with repeated measures. SETTING Outpatient radiation oncology department in a metropolitan public teaching hospital in Western Australia. SAMPLE 126 adult women aged 30-78 receiving postlumpectomy radiation therapy for breast cancer. METHODS Data about potential predictive factors were collected during the first week of radiation. Weekly observations of the skin reaction using the Radiation Therapy Oncology Group scoring system were recorded throughout treatment with an inter-rater reliability of 0.85. RESULTS Chi square analysis and t-tests revealed many factors related to severe skin reactions on a univariate level. Logistic regression analysis calculated the relative risk and probability of developing a severe skin reaction. Predictive factors included weight, breast size, lymphocele aspiration, smoking, age, skin cancer, tumor stage, and radiation dose. CONCLUSIONS In addition to radiation dose, some factors that impair wound healing also contribute to the cause of patient-to-patient variation, thus making it possible to predict who is likely to develop a severe skin reaction. IMPLICATIONS FOR NURSING PRACTICE The findings will assist in individualizing the assessment, education, and management of women undergoing radiation therapy for breast cancer. Further research could lead to the development of a method of risk assessment for skin reactions for use in radiation therapy nursing.
Hip Arthroscopy for Femoroacetabular Impingement: Results of 118 Consecutive Cases in a District General Hospital

Femoroacetabular impingement (FAI) is an increasingly recognised cause of hip symptoms in the young active adult and can lead to labral tears and chondral damage. FAI can be treated with open surgery or arthroscopically: aiming to stabilise labral tears and remove bony impingement. We report the results of a single surgeon series of arthroscopic labral debridement and cam resection in 118 consecutive cases during a two-year period, with a minimum follow-up of one year. Quantitative assessment was undertaken using the Non-Arthritic Hip Score (NAHS) calculated preoperatively and at two, four and 12 months postoperatively. Mean NAHS in all patient groups at two and four months, and at one year showed improvement (p<0.05). These results compare favourably with previous patients treated with open osteochondroplasty by the same surgeon, as well as with the published results from other larger centres. The faster improvement and the shorter hospital stay and lower morbidity make arthroscopic surgery for FAI a favourable option, and a feasible treatment modality in the non-specialist setting.
Effectiveness and cost of the inpatient treatment of posttraumatic stress disorder: comparison of three models of treatment.

OBJECTIVE This study compared the outcomes and costs of three models of Department of Veterans Affairs (VA) inpatient treatment for posttraumatic stress disorder (PTSD): 1) long-stay specialized inpatient PTSD units, 2) short-stay specialized evaluation and brief-treatment PTSD units, and 3) nonspecialized general psychiatric units. METHOD Data were drawn from 785 Vietnam veterans undergoing treatment at 10 programs across the country. The veterans were followed up at 4-month intervals for 1 year after discharge. Successful data collection averaged 66.1% across the three follow-up intervals. RESULTS All models demonstrated improvement at the time of discharge, but during follow-up symptoms and social functioning rebounded toward admission levels, especially among participants who had been treated in long-stay PTSD units. Veterans in the short-stay PTSD units and in the general psychiatric units showed significantly more improvement during follow-up than veterans in the long-stay PTSD units. Greatest satisfaction with their programs was reported by veterans in the short-stay PTSD units. Finally, the long-stay PTSD units proved to be 82.4% and 53.5% more expensive over 1 year than the short-stay PTSD units and general psychiatric units, respectively. CONCLUSIONS The paucity of evidence of sustained improvement from costly long-stay specialized inpatient PTSD programs and the indication of high satisfaction and sustained improvement in the far less costly short-stay specialized evaluation and brief-treatment PTSD programs suggest that systematic restructuring of VA inpatient PTSD treatment could result in delivery of effective services to larger numbers of veterans.
Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

Influenza A virus (IAV) infection results in a highly contagious respiratory illness leading to substantial morbidity and occasionally death. In this report, we assessed the in vivo physiological contribution of invariant NKT (iNKT) lymphocytes, a subset of lipid-reactive αβ T lymphocytes, on the host response and viral pathogenesis using a virulent, mouse-adapted, IAV H3N2 strain. Upon infection with a lethal dose of IAV, iNKT cells become activated in the lungs and bronchoalveolar space to become rapidly anergic to further restimulation. Relative to wild-type animals, C57BL/6 mice deficient in iNKT cells (Jα18−/− mice) developed a more severe bronchopneumonia and had an accelerated fatal outcome, a phenomenon reversed by the adoptive transfer of NKT cells prior to infection. The enhanced pathology in Jα18−/− animals was not associated with either reduced or delayed viral clearance in the lungs or with a defective local NK cell response. In marked contrast, Jα18−/− mice displayed a dramatically reduced IAV-specific CD8+ T cell response in the lungs and in lung-draining mediastinal lymph nodes. We further show that this defective CD8+ T cell response correlates with an altered accumulation and maturation of pulmonary CD103+, but not CD11bhigh, dendritic cells in the mediastinal lymph nodes. Taken together, these findings point to a role for iNKT cells in the control of pneumonia as well as in the development of the CD8+ T cell response during the early stage of acute IAV H3N2 infection.
Relationship between physical activity, socioeconomic status, and physical fitness of 8–15‐year‐old youth from Mozambique

A cross‐sectional study of 593 students (277 boys, 316 girls) 8–15 years of age was done to evaluate the physical fitness (PF) of children and adolescents from Maputo, Mozambique, relative to socioeconomic status (SES) and physical activity (PA). PF was assessed by a battery of field tests including the sit and reach, sit‐ups, hand grip strength, a 10 × 5 meters shuttle run, and two distance runs, 1,600 and 2,400 meters. PA was estimated with a questionnaire designed for this population. Students were divided into three groups according to region of residence, which was used as the criterion of SES. PA was more intense among underprivileged students due to domestic activities and walking time per day. PF significantly differed among SES groups. Poor students exhibited significantly better results on the sit and reach and endurance runs, while privileged children performed better on sit‐ups and the shuttle run. There were no differences in grip strength. Comparison with North American reference data suggests that Mozambican youth have greater flexibility and cardiorespiratory endurance, but less absolute strength and power. The results suggest that SES is an important determinant of fitness in Mozambique, especially because of its influence on body size, composition, and on PA. In addition, cultural effects on the performance of the tests were indicated. Am. J. Hum. Biol. 9:449–457, 1997. © 1997 Wiley‐Liss, Inc.
Respiration features of Chinese learners under self-narration task — The case of learners from Korea, Japan, America and Thailand

Through the methods of physiological experiment in combination with acoustical experiment, the present research investigates the respiration and acoustic features of the Chinese learners during the task of self-narration. Twenty-four Chinese learners from Korea, Japan, America and Thailand are assigned to narrate in Mandarin Chinese. The spontaneous speech respiration which is greatly influenced by the physiological condition, cognitive processing, context and mood state tends to make the respiration curve to be complex. In this condition, compared with Chinese native speakers, different respiratory units have significant differences in inspiration/expiration duration, amplitude and slope in terms of respiratory parameters. The frequency of the abnormal pause is large in great extent, and the position of the abnormal pause is rather flexible, so its different categories correspond to the different respiration forms.
Common structural features of toxic intermediates from &agr;-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging

The aggregation and deposition of &agr;-synuclein (&agr;Syn) in neuronal cells is correlated to pathogenesis of Parkinson’s disease. Although the mechanism of &agr;Syn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of &agr;Syn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed &agr;Syn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of &agr;Syn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both &agr;Syn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of &agr;Syn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.
Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells

Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle-controlling genes and forms distinct heteromeric complexes with other nuclear proteins. We show here that alpha and beta interferons (alpha, beta) and interleukin-6 abolished the E2F-containing DNA-binding complexes in Daudi Burkitt lymphoma cells and in M1 myeloblastic cells, which responded to the cytokines by suppression of c-myc transcription. Time kinetics studies showed that the abolishment of E2F complexes coincided with reduction of c-myc expression and that both molecular events preceded the cell cycle block in G0/G1 phase. In contrast, the pattern of E2F complexes remained unchanged in an interferon-treated growth-resistant Daudi cell mutant that displayed relaxed regulation of c-myc. All of the DNA-binding E2F complexes, including those containing the retinoblastoma protein (pRB), cyclin A-p33cdk2, and the free forms of E2F, were reduced by interferons or interleukin-6. Their abolishment was unperturbed by pharmacological treatments that alleviated the cyclin A and pRB responses to interferon. Thus, changes in cyclin A expression and pRB phosphorylation are not primary events that influence the pattern of E2F responses to cytokines. Addition of EDTA to cell extracts of interferon-treated Daudi cells restored the DNA-binding activity of E2F, resulting in the appearance of a single E2F complex that exclusively contained pRB. It is suggested that the regulation of E2F by growth-inhibitory cytokines that induce cell cycle exit takes place at the level of the DNA-binding activity, and by that mean it differs basically from the phase-specific regulation of E2F in cycling cells.