Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH 1 acting as a highly potent antioxidant agent

The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age‐ and disease‐related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on‐site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the β‐amyloid peptide, hydrogen peroxide and 3‐hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 μm significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti‐ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co‐administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.
The Clinical Pharmacokinetics of Quinapril

Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose pro portional following single oral 2.5- to 80-mg Q doses. Q absorption and hy drolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL follow ing 40-mg Q). Dose-proportional QT area under the curve and dose-inde pendent percent of dose excreted in urine as QT demonstrate that the ex tent of Q conversion to QT is con stant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clear ances of 1,850 and 220 mL/min, re spectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactiv ity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketo piperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an admin istered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary ex cretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clear ance of both Q and QT is independ ent of dose, and metabolism to compounds other than QT is not ex tensive.
The Medical Library Association Benchmarking Network: development and implementation.

OBJECTIVE This article explores the development and implementation of the Medical Library Association (MLA) Benchmarking Network from the initial idea and test survey, to the implementation of a national survey in 2002, to the establishment of a continuing program in 2004. Started as a program for hospital libraries, it has expanded to include other nonacademic health sciences libraries. METHODS The activities and timelines of MLA's Benchmarking Network task forces and editorial board from 1998 to 2004 are described. RESULTS The Benchmarking Network task forces successfully developed an extensive questionnaire with parameters of size and measures of library activity and published a report of the data collected by September 2002. The data were available to all MLA members in the form of aggregate tables. Utilization of Web-based technologies proved feasible for data intake and interactive display. A companion article analyzes and presents some of the data. MLA has continued to develop the Benchmarking Network with the completion of a second survey in 2004. CONCLUSIONS The Benchmarking Network has provided many small libraries with comparative data to present to their administrators. It is a challenge for the future to convince all MLA members to participate in this valuable program.
Relationship Between Depression in Patients With COPD and the Percent of Predicted FEV1, BODE Index, and Health-Related Quality of Life

BACKGROUND: We investigated the prevalence of depression among patients with COPD treated in long-term in-patient rehabilitation facilities, using the Center for Epidemiologic Studies Depression scale (CES-D). Furthermore, the relationship between the severity of air-flow obstruction (the percent of predicted FEV1), BODE (body mass index, degree of air-flow obstruction, dyspnea, exercise capacity) index, health-related quality of life (St George's Respiratory Questionnaire [SGRQ]), and depression were investigated. METHODS: We recruited 74 in-patients (64 males, 10 females) with COPD. The mean age of the subjects was 72.7 years (range 52–85 y). Subjects completed the CES-D, and measurements were made of pulmonary function, body mass index, Modified Medical Research Council dyspnea scale, 6-min walk test (6MWT), and SGRQ. RESULTS: Depression was evident in 48.6% (n = 36) of the subjects. A weak correlation was found between the CES-D scores and the percent of predicted FEV1. The prevalence of depression showed a significant association with BODE stage. Scores for the SGRQ activity and impacts domains, and total SGRQ score were significantly worse in the subjects who were depressed. CONCLUSIONS: We found a high prevalence of depression among patients with stable COPD treated in long-term in-patient rehabilitation facilities. Depression among these patients, as measured by the CES-D, was associated with greater impairment in respiratory function and with poorer Modified Medical Research Council dyspnea scale and SGRQ scores. The prevalence of depression increased with BODE stage.
The molecular origin of the MMR-dependent apoptosis pathway from dynamics analysis of MutSα-DNA complexes

The cellular response to DNA damage signaling by mismatch-repair (MMR) proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR’s DNA repair function. In this study, we investigate correlated motions in response to the binding of mismatched and platinum cross-linked DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations. The protein dynamics in response to the mismatched and damaged DNA recognition suggests that MutSα signals their recognition through independent pathways providing evidence for the molecular origin of the MMR-dependent apoptosis. MSH2 subunit is indicated to play a key role in signaling both mismatched and damaged DNA recognition; localized and collective motions within the protein allow identifying sites on the MSH2 surface possible involved in recruiting proteins responsible for downstream events. Unlike in the mismatch complex, predicted key communication sites specific for the damage recognition are on the list of known cancer-causing mutations or deletions. This confirms MSH2’s role in signaling DNA damage-induced apoptosis and suggests that defects in MMR alone is sufficient to trigger tumorigenesis, supporting the experimental evidence that MMR-damage response function could protect from the early occurrence of tumors. Identifying these particular communication sites may have implications for the treatment of cancers that are not defective for MMR, but are unable to function optimally for MMR-dependent responses following DNA damage such as the case of resistance to cisplatin.
Energy Use: Electricity System in West Africa and Climate Change Impact

This article investigates a low carbon pathway, the theoretical frame for understanding the trade-offs between economic development and climate change. An already developed model - Electricity Planning-Low Carbon Development (EP-LCD) - was adapted and modified to examine the nonlinear relationship between generation adequacy and greenhouse gas (GHG) emission reduction for better targeted strategic regional intervention on climate change. Two broad scenarios - Base and LCD Option - were tested for the West African Power Pool (WAPP). The cost impact of increasing generation capacity in the LCD Option was estimated at US$1.54 trillion over a 50 year period. Achieving the goal of low carbon pathway would be largely influenced by government decision. Four strategies, in line with the Nationally Determined Contribution in Paris Agreement, were recommended. These are: a) enforced improved efficient electricity generation through increased energy efficiency that should result in increased capacity factor; b) decreased energy intensity of economic activities to result in reduced emission factor in existing plants; c) attract new investment through low tax or tax exemption to reduce cost of constructing power plants for the benefit of base-load plants; and d) subsidized cost of low-carbon fuels in the short run to benefit intermediate load plants and allow for the ramping up of low-/no-carbon fuel generation capacity. These are recommended considering the region’s specific economical and political conditions where funds are tremendously difficult to raise. Implementing these recommendations will allow the electric power industry in West Africa to contribute to achieving sustainable development path.
The use of meconia to nondestructively detect sublethal infections in heliothines (Lepidoptera: Noctuidae).

The utility of using meconia to nondestructively detect entomopathogens of lepidopterous heliothines was examined. Early-instar tobacco budworm [Heliothis virescens (F.)] or cotton bollworm [Helicoverpa zea (Boddie)] larvae were inoculated with cytoplasmic polyhedrosis virus (CPV), Serratia marcescens Bizio, or Nosema heliothidis Lutz and Splendor, and the presence of each of the entomopathogens in adults and the meconia discharged during adult eclosion was determined. As the dose of CPV occlusion bodies and N. heliothidis spores but not S. marcescens cells ingested by larvae increased, a greater number of both adults and meconia were infested with the entomopathogens. For all three entomopathogens, no difference was observed between males and females for any of the parameters tested. The accuracy of the meconium method for predicting the presence of the entomopathogens in the adults (i.e., number of individuals in which meconia and adults were both positive, or meconia and adults were both negative) was > or = 92% for CPV, and > or = 79% for S. marcescens and N. heliothidis. Very few false negative predictions (i.e., the meconium was negative but the adult was positive) were observed for CPV (< or = 1%). The prevalence of false negative predictions ranged from 2 to 9%, and 5 to 21% for S. marcescens and N. heliothidis, respectively. The prevalence of false positive predictions (i.e., the meconium was positive but the adult was negative) was < or = 7% for CPV, < or = 13% for S. marcescens, and 0% for N. heliothidis. The results of this study demonstrate that although not absolute, the meconium method will be an efficacious method to detect nondestructively entomopathogens causing sublethal infections in heliothines, and possibly other insects, and thereby facilitate the rearing of specific pathogen free insects.
Rapidly alternating photoperiods disrupt central and peripheral rhythmicity and decrease plasma glucose, but do not affect glucose tolerance or insulin secretion in sheep

What is the central question of this study? Disrupting circadian rhythms in rodents perturbs glucose metabolism and increases adiposity. In this study, we asked whether circadian rhythm disruption, induced by exposure of sheep to rapidly alternating photoperiods (RAPs), also disrupts metabolic homeostasis in a large diurnal animal model. What is the main finding and its importance? Exposure to RAPs disrupted central (melatonin and core body temperature) and peripheral rhythmicity (skeletal muscle clock gene expression). This led to reduced nocturnal plasma glucose concentrations, but did not affect glucose tolerance and glucose‐stimulated insulin secretion. These results suggest that RAP‐induced circadian rhythm disruption has minimal effect on glucose homeostasis in the sheep.
Autologous and allogeneic mesenchymal stem cells in organ transplantation: what do we know about their safety and efficacy?

Purpose of reviewRecent developments toward the successful clinical application of autologous and allogeneic mesenchymal stem cells (MSCs) to organ transplantation are summarized with a focus on safety and efficacy. Recent findingsClinical trials in organ transplantation and other conditions indicate that infusion of autologous or allogeneic MSCs is generally well tolerated. However, new studies also suggest that efficacy may be curtailed by sequestration in the lungs and early elimination. Safety concerns regarding autologous and/or allogeneic MSCs that have recently been investigated include transient proinflammatory effects, influences on opportunistic infections and cancers and alloantibody induction. Animal models indicate that autologous MSCs are likely to be efficacious in preventing or treating early intragraft inflammation and may reduce the risk of acute rejection – observations that have been borne out in a randomized controlled trial of living-donor kidney transplantation. The potential for donor-specific or third-party allogeneic MSCs to promote allograft tolerance is suggested by animal model studies but has not yet been proven in humans. Summary: Recent reports on the safety and efficacy of autologous MSCs for early posttransplant outcomes give cause for optimism. Benefits of allogeneic MSCs for long-term allograft survival and of MSCs for chronic transplant injury await clinical validation.
Financial and non-financial determinants of corporate social responsibility: empirical evidence from Pakistan

The purpose of this research study is to lower the knowledge gap by exploring the degree of corporate social responsibility disclosures (CSRD) made by top Pakistani (Karachi Stock Exchange [KSE] 100 listed non-financial) companies and investigating the financial and non-financial CSRD determinants which aid to the policy development in implementing required regulatory reforms. ,KSE 100 index listed companies are covered in this study that published their annual reports consistently during the time period of five years from 2009 to 2013. Financial and non-financial data will be collected from the sample of KSE-listed company’s annual reports. Information related to corporate social responsibility (CSR) will be collected by hand from reports of disclosure of CSR, disclosures of corporate governance, report of the directors, a statement of Chairman’s and notes to the financial statement enclosed in companies’ annual reports. Content analysis technique to measure corporate environmental and social disclosures for items scoring the approach is, in essence, dichotomous, one score assigned to the item in the scores of instrument of research if it disclosed, otherwise assigned zero, and no penalty or negative score is imposed to the item which is reflected irrelevant. ,Family ownership, industry type and firm size have positive significant relationship with CSR disclosure, and the authors found negative significant relationship between risk and CSRD. Results of this study propose that, in developing countries like Pakistan, the extent of determinant of CSRD is based on the number of important firm and industry characteristics and are aligned with empirical evidence. ,This research uses only annual reports of the companies for the data of CSRD but companies also use other sources for disclosure of their CSR information such as mass media, etc. Content analysis is performed by one author and the second author cross-checked the companies, so biasness may remain a limitation due to the fact that errors attach in rating scale due to judgments of human. ,The finding of this study helps policymakers to quantify and know the degree of CSRD and its determinants which enables them to boost the organizational legitimacy and CSR practices by adopting the needed regulatory reform. ,The results of this study provide warning signals to the management of the companies in some cases where disclosure level of CSR is lower in the period before issuance of SECP CSR guidelines of 2013. ,This research study offers valuable inputs in the development and betterment of CSR rules for the reason that the findings of the research provide information to the future CSR rules and guidelines. The results of this study also help the regulator (SECP) in Pakistan to revise the CSRD to align with the need of changing industrial characteristics and economic environment.
Pretransplantation GAD-Autoantibody Status to Guide Prophylactic Antibody Induction Therapy in Simultaneous Pancreas and Kidney Transplantation

Background Daclizumab and antithymocyte globulin (ATG) have been shown to reduce allograft rejection. We assessed the safety and efficacy of daclizumab or ATG prophylaxis in combination with triple immunotherapy in simultaneous pancreas-kidney transplant (SPKT) recipients. Methods Thirty-nine type 1 diabetic patients scheduled for primary SPKT were randomized to receive prophylactic therapy with either daclizumab or ATG. A group of 27 patients without prophylactic antibodies was used for retrospective comparison. All patients received cyclosporine and mycophenolate mofetil and gradually tapered prednisone. Autoantibodies and cellular autoreactivity were measured to assess recurrent autoreactive responses. Results Baseline and transplant characteristics were comparable among groups. Both daclizumab and ATG therapy resulted in a significant reduction in acute rejection episodes. The incidence of rejection episodes was significantly higher in pretransplantation GAD autoantibody-positive daclizumab-treated recipients compared with GAD autoantibody-negative or ATG-treated recipients. IA-2 islet autoantibodies showed no association with rejection. There were no significant differences between the groups for in vitro autoreactivity, clinical outcome, or functional parameters. Conclusions Daclizumab or ATG combined with a maintenance immunosuppressive regime consisting of cyclosporine, mycophenolate mofetil, and prednisolone were well tolerated and equally effective in reducing the incidence of acute rejection episodes in SPKT recipients. Up to 3 years, no adverse sequelae of the immunoprophylaxis or clinical and ex vivo recurrent autoimmunity were observed. We propose that the pretransplantation existence of GAD65 autoantibodies serves as a marker guiding the choice for prophylactic therapy in pancreas transplantation.
Intraspinal administration of human spinal cord‐derived neural progenitor cells in the G93A–SOD1 mouse model of ALS delays symptom progression, prolongs survival and increases expression of endogenous neurotrophic factors

Neural stem or progenitor cells are considered to be a novel therapeutic strategy for amyotrophic lateral sclerosis (ALS), based on their potential to generate a protective environment rather than to replace degenerating motor neurons. Following local injection to the spinal cord, neural progenitor cells may generate glial cells and release neurotrophic factors. In the present study, human spinal cord‐derived neural progenitor cells (hscNPCs) were injected into the lumbar spinal cord of G93A–SOD1 ALS transgenic mice. We evaluated the potential effect of hscNPC treatment by survival analysis and behavioural/phenotypic assessments. Immunohistological and real‐time PCR experiments were performed at a defined time point to study the underlying mechanisms. Symptom progression in hscNPC‐injected mice was significantly delayed at the late stage of disease. On average, survival was only prolonged for 5 days. Animals treated with hscNPCs performed significantly better in motor function tests between weeks 18 and 19. Increased production of GDNF and IGF‐1 mRNA was detectable in spinal cord tissue of hscNPC‐treated mice. In summary, treatment with hscNPCs led to increased endogenous production of several growth factors and increased the preservation of innervated motor neurons but had only a small effect on overall survival. Copyright © 2015 John Wiley & Sons, Ltd.
The punishment marketplace: Competing for capitalized power in locally controlled immigration enforcement

Neoliberal economics play a significant role in US social organization, imposing market logics on public services and driving the cultural valorization of free market ideology. The neoliberal ‘project of inequality’ is upheld by an authoritarian system of punishment built around the social control of the underclass—among them unauthorized immigrants. This work lays out the theory of the punishment marketplace: a conceptualization of how US systems of punishment both enable the neoliberal project of inequality, and are themselves subject to market colonization. The theory describes the rescaling of federal authority to local centers of political power. Criminal justice policy activism by local governments is punishment entrepreneurship: an accumulative approach to securing fiscal gain, political hegemony, security, and capitalized power. Local immigration enforcement entrepreneurship targets unauthorized and other deportable immigrants. This punitive immigration control reinforces racially structured social relations by obscuring the diminishing returns neoliberal globalization provides working class whites.
Changes in Cerebral Microcirculation During and After Abdominal Aortic Cross-Clamping in Rabbits: The Role of Thromboxane A2 Receptor

Little is known about any changes in cerebral hemodynamics, during and after abdominal aortic cross-clamping and unclamping, especially in the cerebral microcirculation. We studied the effects of abdominal aortic cross-clamping and unclamping on cerebral pial vessel diameter in the presence or absence of the thromboxane (Tx)A2 receptor antagonist using a closed cranial window in 27 rabbits. Although infrarenal aortic cross-clamping did not affect pial vessel diameter, release of a 20-min aortic cross-clamp caused pial arterioles to dilate and then constrict. A significant constriction persisted for at least 60 min (maximum, −17% for large [≥75 &mgr;m] and −28% for small arterioles [<75 &mgr;m] compared with baseline). Topical administration of a TxA2 receptor antagonist, seratrodast, at 10−7 M and 10−6 M, significantly attenuated the constriction of large and small arterioles (at 60 min, −9% and −13% constriction for 10−7 M, and −6% and −7% for 10−6 M). Release of a 20-min aortic cross-clamp induced a sustained pial arteriolar constriction. Because this unclamping-induced vasoconstriction was attenuated by topical administration of seratrodast, it was likely partially mediated via the washout of TxA2 produced in the ischemic region during the clamp and after cross-clamp release.