Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of traditional antidiabetic medicinal plants of mauritius for possible α‐amylase inhibitory effects in vitro

In this study, seven exotic/indigenous medicinal plants of Mauritius, namely Coix lacryma‐jobi (Poaceae), Aegle marmelos (Rutaceae), Artocarpus heterophyllus (Moraceae), Vangueria madagascariensis (Rubiaceae), Azadirachta indica (Meliaceae), Eriobotrya japonica (Rosaceae) and Syzigium cumini (Myrtaceae) were studied for possible effects on starch breakdown by α‐amylase in vitro. The results showed that only Artocarpus heterophyllus significantly (p < 0.05) inhibited α‐amylase activity in vitro. To confirm the observed effects, a further biochemical assay was undertaken to investigate the effects of Artocarpus heterophyllus on α‐amylase activity using rat plasma in vitro. It was found that the aqueous leaf extract significantly (p < 0.05) inhibited α‐amylase activity in rat plasma. The highest inhibitory activity (27.20 ± 5.00%) was observed at a concentration of 1000 µg/mL. However, in both cases dose dependency was not observed. Enzyme kinetic studies using the Michaelis‐Menten and Lineweaver‐Burk equations were performed to establish the type of inhibition involved. In the presence of the plant extract the maximal velocity (Vmax) remained constant (1/150 g / L/s) whereas the Michaelis‐Menten constant (Km) increased by 5.79 g / L, indicating that the aqueous leaf extract of Artocarpus heterophyllus behaved as a competitive inhibitor. Results from the present study tend to indicate that Artocarpus heterophyllus could act as a ‘starch blocker’ thereby reducing post‐prandial glucose peaks. Copyright © 2006 John Wiley & Sons, Ltd.
Dosing Regimen Matters: the Importance of Early Intervention and Rapid Attainment of the Pharmacokinetic/Pharmacodynamic Target

ABSTRACT To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent suboptimal systemic drug concentrations prior to the attainment of a steady state. Suboptimal (inadequate) exposure can produce amplification of resistant bacteria. This minireview provides an overview of published evidence supporting the positions that, in most situations, it is the exposure achieved during the first dose that is relevant for determining the therapeutic outcome of an infection, therapeutic intervention should be initiated as soon as possible to minimize the size of the bacterial burden at the infection site, and the duration of drug administration should be kept as brief as clinically appropriate to reduce the risk of selecting for resistant (or phenotypically nonresponsive) microbial strains. To support these recommendations, we briefly discuss data on inoculum effects, persister cells, and the concept of time within some defined mutation selection window.
Cerebral Edema in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Background Cerebral edema (CED) deteriorates outcome of ischemic stroke patients, and there is no effective medical treatment. Limited data exist on cerebral edema after stroke thrombolysis. Aims We aimed to analyze impact of cerebral edema on the outcome of thrombolysis-treated patients. Methods Our cohort included 943 thrombolysis-treated ischemic stroke patients at the Helsinki University Central Hospital (1995–2008). Cerebral edema represented focal brain swelling up to 1/3 (CED-1) or greater than 1/3 (CED-2) of the hemisphere, or midline shift (CED-3). We studied baseline parameters associated with development of cerebral edema and association of cerebral edema with three-month outcome (modified Rankin Scale, mRS). Results On control imaging, CED-1 was present in 167 (17·7%), CED-2 in 40 (4·2%), and CED-3 in 53 (5·6%) patients. Compared with patients without edema (n = 683), patients with cerebral edema had higher baseline National Institutes of Health Stroke Scale scores, more often hyperdense cerebral artery sign or early infarct signs on admission computerized tomography, and received thrombolysis later. Cerebral edema was independently associated with poor outcome (mRS 3–6) and mortality, whereas favorable outcome (mRS 0–2) was observed in 77 (46%), 5 (13%), and 3 (6%) patients with CED 1, 2, and 3, respectively. Anti-edema treatment was considered necessary and administered to 49/260 (19%) patients; only five had favorable outcome. Conclusions Cerebral edema is frequent (28%) among thrombolysis-treated ischemic stroke patients, occurring in severe forms in 10%. Higher baseline National Institutes of Health Stroke Scale, presence of hyperdense cerebral artery sign or early infarct signs, and longer treatment delays are associated with edema development. Edema is a strong independent predictor of three-month outcome. Effect of anti-edema treatment was modest.
Clock Time and Embodied Time Experienced by Patients With Inoperable Lung Cancer

In this study, we explore how patients with inoperable lung cancer (LC) discuss their experiences of time, based on content analysis of open interviews with 35 patients 1 year after diagnosis, using Davies' distinction between "clock time" and "embodied time" as sensitizing concepts. Two interrelated themes were derived: (1) aspects related to the healthcare system, with 3 subthemes: waiting times in the healthcare system, limited time for patient-professional contact, and limited time for coordination of services, and (2) existential aspects, with subthemes: the future with LC and managing an uncertain and finite life with LC. Time could be experienced as problematic for these patients, when limited or lacking or through long periods of waiting, especially when these periods occurred without adequate preparation or information. This contributed to exacerbation of these patients' existing sense of uncertainty, their perception of care as impersonal and insecure, and their need to remain alert and act on their own behalf. Awareness of the seriousness of their disease and the prospect of a limited lifetime was described as increasing uncertainty about dying and fear of certain death. People also described efforts to constructively deal with their situation by reprioritizing their remaining time, having increased appreciation of some aspects of daily life, and living consciously in the present. This analysis suggests a collision between clock time, which steers the healthcare system, and embodied time, as experienced by individuals. Greater attention to psychosocial needs is suggested as one means of positively affecting patients' experiences of time and uncertainty.
Effect of Choline-Containing Phospholipids on Transglutaminase Activity in Primary Astroglial Cell Cultures

The aim of the present investigation was to study the effects of choline and choline-containing phospholipids CDP-choline (CDPC) and L-alpha-glyceryl-phosphorylcholine (AGPC) on transglutaminase (TG) activity and expression in primary astrocyte cultures. TG is an important Ca2+-dependent protein that represents a normal constituent of nervous systems during fetal stages of development, playing a role in cell signal transduction, differentiation, and apoptosis. Confocal laser scanning microscopy (CLSM) analysis showed an increase of TG activity in astrocyte cultures treated with choline, CDPC, or AGPC at 0.1 μM or 1 μM concentrations. Comparatively, AGPC induced the most conspicuous effects enhancing monodansyl-cadaverine fluorescence both in cytosol and in nuclei, supporting the evidence of the important role played by AGPC throughout differentiation processes tightly correlated to nucleus-cytosol cross- talk during astroglial cells proliferation and development. Western blot analysis showed that in 24h 1 μM AGPC and choline-treated astrocytes increased TG-2, whereas no effect was observed in 24h 1 μM CDP-choline treated astrocytes. Our data suggest a crucial role of choline precursors during different stages of astroglial cell proliferation and differentiation in cultures.
Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose, 800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment. RESULTS At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin. CONCLUSION This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.
Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective.

CONTEXT Mutation status of the KRAS gene identifies a distinct disease subtype of metastatic colorectal carcinoma that does not respond to antibody therapeutics targeting the epidermal growth factor receptor. This is currently the only validated marker in metastatic colorectal carcinoma with a clear implication in treatment selection. KRAS testing is widely accepted in clinical practice to guide metastatic colorectal carcinoma therapeutic decisions, and there are many commercially available platforms to perform the test. OBJECTIVE To evaluate the critical role of pathologists in the full implementation of KRAS testing by optimizing tumor tissue collection and fixation procedures and by choosing testing technologies and reliable Clinical Laboratory Improvement Amendments of 1988-certified laboratories to perform the tests. DATA SOURCES Prospective clinical trials, retrospective studies, and quality assessment and survey reports were identified in the following databases: PubMed, American Society of Clinical Oncology Proceedings (American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancer Symposium) and European Society for Medical Oncology Proceedings (Annals of Oncology European Society for Medical Oncology Congress and Annals of Oncology World Congress on Gastrointestinal Cancers). CONCLUSIONS More bona fide standards are needed to address the variety of available test methods, which have different performance characteristics including speed, sensitivity to detect rare mutations, and technical requirements. Refined standards addressing timing of KRAS testing, laboratory performance and accuracy, quality assurance and control, proper tissue collection, and appropriate result reporting would also be greatly beneficial. Pathologists should be aware that the amount of information they need to manage will increase, because future trends and technological advances will enhance the predictive power of diagnostic tests or the scope of the biomarker panels tested routinely across tumor types.
Flagellin Gene Polymorphism Analysis of Campylobacter Compared with Antigen Serotyping

Abstract Flagellin gene sequence polymorphisms were used to discrimate amongst 53 strains of Campylobacter jejuni and C. coli. The Campylobacter strains were made up of forty-three strains of Campylobacter jejuni and 10 strains of Campylobacter coli. The results were analysed in relation to Penner serotyping. Twenty DNA PCR -RFLP patterns (genotypes) were identified by analysis of Dde I fragment length polymorphisms in flagellin gene (fla A and fla B) polymerase chain reaction (PCR) products. Flagellin gene 13 genotype was a feature of 15% of strains, followed by flagellin gene 8 (9 %). Differences in fragment patterns were observed not only between members of two species, but also between individual strains of the same species. The strains that were non-typable by the Penner serotype were distributed into 6 flagellin gene types. In conclusion, Dde I fla typing is reproducible and offers high typability. However, when the scheme is used in combination with the Penner serotype it provides improved discrimination for the characterizing and subtyping of isolates.
Natural history of impetigo. II. Etiologic agents and bacterial interactions.

Intensive observations on 37 children in a population with endemic skin infections provided an opportunity to study the interrelationships between and the significance of the bacterial genera commonly associated with impetigo. Cultures of the respiratory tract, three normal skin sites, and lesions, when present, were taken three times weekly from July to October 1969. Impetigo developed in all 37 children. Group A streptococci alone were recovered from 21% of 361 lesions, Staphylococcus aureus alone from 8%, Staphylococcus epidermidis alone from 5% and mixtures of streptococci and staphylococci from 61%. Vesicular or pustular lesions were more often pure streptococcal than pure staphylococcal. Streptococci alone were more often recovered from early stage lesions rather than from later ones. The pure staphylococcal lesions characteristically occurred early in the season whereas streptococcal or mixed lesions had later peaks.Serial observations on 74 lesions revealed longer persistence of streptococci than staphylococci in mixed lesions. In 85% of the instances the same streptococcal serotype was recovered repeatedly from an individual lesion, whereas staphylococcal types changed in 57% of instances. Phage type 75 accounted for the majority of staphylococcal isolates from all sites, whereas phage type 54 was recovered only from skin lesions. In contrast to streptococci, the site sequence of staphylococcal spread was from the nose to normal skin to skin lesions. These studies reveal important differences in the migration of staphylococci (as compared with streptococci) to various body sites and suggest a subsidiary role for staphylococci in nonbullous impetiginous lesions yielding both organisms.
Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R study.

CONTEXT Abnormal maternal thyroid parameters are associated with adverse pregnancy outcomes, with consequences for both mother and child. Although various studies have studied maternal thyroid parameters during the first half of pregnancy, little is known about their relations with thyroid parameters of the child. OBJECTIVE The objective was to study maternal thyroid parameters during the first half of pregnancy as well as their relations with cord thyroid parameters. DESIGN, SETTING, AND PARTICIPANTS Serum TSH, free T(4) (FT4), T(4), and thyroid peroxidase antibody (TPOAb) levels were determined once between gestational wk 9 and 18 in 5393 pregnant women from the population-based Generation R study. Cord serum TSH and FT4 levels were determined in 3036 newborns. RESULTS Between gestational wk 9 and 18, the maternal TSH reference range (2.5th to 97.5th percentile) was 0.03-4.04 mU/liter. Gestational age was positively correlated with maternal TSH (r = 0.06, P = 6.3 × 10(-5)) and total T(4) (r = 0.21, P = 1.4 × 10(-44)) and negatively with FT4 (r = -0.27, P=7.3 × 10(-76)) and TPOAb-positivity (r=-0.04, P = 0.01). TPOAb positivity was associated with more subclinical (20.1 vs. 2.4%, P = 1.5 × 10(-39)) and overt hypothyroidism (3.3 vs. 0.1%, P = 1.4 × 10(-10)). Maternal and cord TSH were positively associated (β = 0.47 ± 0.15, P = 1.3 × 10(-5)) as well as maternal and cord FT4 (β = 0.11 ± 0.02, P = 4.5 × 10(-6)). CONCLUSIONS We confirm correlations of maternal thyroid parameters with gestational age during the first half of pregnancy and show a substantially increased risk of (subclinical) hypothyroidism in TPOAb-positive mothers. A substantial part of the mothers had a TSH level above 2.5 mU/liter, underlining the importance of using population-specific reference ranges. Maternal and cord thyroid parameters were positively correlated, the exact biological basis of which remains to be determined.
Efficient Computation and Covariance Analysis of Geometry-Based Stochastic Channel Models

In this work, we study a family of wireless channel simulation models called geometry-based stochastic channel models (GBSCMs). Compared to more complex ray-tracing simulation models, GBSCMs do not require an extensive characterization of the propagation environment to provide wireless channel realizations with adequate spatial and temporal statistics. The trade-off they achieve between the quality of the simulated channels and the computational complexity makes them popular in standardization bodies. Using the generic formulation of the GBSCMs, we identify a matrix structure that can be used to improve the performance of their implementations. Furthermore, this matrix structure allows us to analyze the spatial covariance of the channel realizations. We provide a way to efficiently compute the spatial covariance matrix in most implementations of GBSCMs. In accordance to wide-sense stationary and uncorrelated scattering hypotheses, this covariance is static in frequency and does not evolve with user movement.
Social entrepreneurs in challenging places: A Delphi study of experiences and perspectives

Social Enterprises have grown in number and scope in response to reductions in state-provided welfare and increasing ambition to improve social conditions. While a range of issues have been identified in the literature as affecting the ability of Social Enterprises to successfully conduct their activities, there is currently a dearth of research into the relative influence of these factors. This study explores and ranks the challenges faced by social entrepreneurs in South Wales. Based on a Delphi study with 21 social entrepreneurs, government policy-developers and scholars, it presents a hierarchy of 14 factors, useful instruments for informing social entrepreneurs and policy-makers about the way social enterprises are managed, and how national and local policy should be developed. As part of this, the study also identifies four novel factors that affect the sustainability of social enterprises: ‘Professionalisation of Marketing’, ‘Perception of Validity’, ‘Leadership’ and ‘Situatedness’.
Securing Social Gains in, Against and Beyond the State: The Case of Denmark’s “Common Housing”

ABSTRACT Public housing is a public sector that has been severely affected by privatization policies. Not so in Denmark, however, where public housing is not provided directly by the State but is run by independent housing associations: the “common housing” sector. This sector is the outcome of a compromise between the social-democratic movement and liberal-conservative parties in the 1920-30s. The social-democrats were politically too weak to implement their “municipal socialism” programme, which included (municipal) State-owned housing. This weakness, however, has in fact proven itself to be strength in the face of recent State-led privatization and mercantilization schemes. This experience problematizes the assumptions underlying the historical construction of the welfare State and its role in stewarding resources that are put in common, particularly in the sphere of housing. Instituting the common beyond the direct reach of the State is a lesson that can be learnt from the demise of social-democratic welfare statism.
The effect of recombinant human fibroblast growth factor‐18 on articular cartilage following single impact load

The aim of this in vitro study was to ascertain the effect of recombinant human Fibroblast Growth Factor‐18 (rhFGF18) on the repair response of mechanically damaged articular cartilage. Articular cartilage discs were harvested from healthy mature horses (n = 4) and subjected to single impact load (SIL). The impacted explants, together with unimpacted controls were cultured in modified DMEM ± 200 ng/ml rhFGF18 for up to 30 days. Glycosaminoglycan (GAG) release into the media was measured using the dimethylmethylene blue (DMMB) assay. Aggrecan neopepitope CS846, collagen type II synthesis (CPII) and cleavage (C2C) were measured by ELISA. Histological analysis and TUNEL staining were used to assess repair cell number and cell death. Impacted explants treated with rhFGF18 showed significantly more GAG and CS846 release into the media (p < 0.05), there was also a significant decrease in C2C levels at Day 20. Loaded sections treated with rhFGF18 had more repair cells and significantly less cell death (p < 0.001) at Day 30 in culture. In an in vitro damage/repair model, rhFGF18 increases the proteoglycan synthesis, the repair cell number and prevents apoptosis at Day 30. This suggests that rhFGF18 may be a good candidate for enhancement of cartilage repair following mechanical damage. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:923–927, 2014.
Toward Universal Coverage in Massachusetts

This paper presents several options designed to help the Commonwealth of Massachusetts move to universal health insurance coverage. The alternatives all build upon a common base that includes an expansion of the Medicaid program, income-related tax credits, a purchasing pool, and government-sponsored reinsurance. These measures in themselves would not yield universal coverage, nor would an employer mandate by itself. We show that an individual mandate, and an employer mandate combined with an individual mandate, both would yield universal coverage with a relatively small increase in government costs relative to state gross domestic product and current health spending. The cost of an employer mandate—with a “pay or play” design—is sensitive to the payroll tax rate and base, the number and kind of exemptions, and whether workers whose employers “pay” receive discounts when they purchase health insurance. The development of these alternatives and their analyses contributed to the eventual health care compromise that emerged in Massachusetts in April 2006.