Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of Hyaluronan Binding Peptides with Glycosaminoglycans in Poly(ethylene glycol) Hydrogels

This study investigates the incorporation of hyaluronan (HA) binding peptides into poly(ethylene glycol) (PEG) hydrogels as a mechanism to bind and retain hyaluronan for applications in tissue engineering. The specificity of the peptide sequence (native RYPISRPRKRC vs non-native RPSRPRIRYKC), the role of basic amino acids, and specificity to hyaluronan over other GAGs in contributing to the peptide–hyaluronan interaction were probed through experiments and simulations. Hydrogels containing the native or non-native peptide retained hyaluronan in a dose-dependent manner. Ionic interactions were the dominating mechanism. In diH2O the peptides interacted strongly with HA and chondroitin sulfate, but in phosphate buffered saline the peptides interacted more strongly with HA. For cartilage tissue engineering, chondrocyte-laden PEG hydrogels containing increasing amounts of HA binding peptide and exogenous HA had increased retention and decreased loss of cell-secreted proteoglycans in and from the hydrogel at 28 days. This new matrix-interactive hydrogel platform holds promise for tissue regeneration.
Ca(2+)-handling proteins and heart failure: novel molecular targets?

Calcium (Ca(2+)) ions are the currency of heart muscle activity. During excitation-contraction coupling Ca(2+) is rapidly cycled between the cytosol (where it activates the myofilaments) and the sarcoplasmic reticulum (SR), the Ca(2+) store. These fluxes occur by the transient activity of Ca(2+)-pumps and -channels. In the failing human heart, changes in activity and expression profile of Ca(2+)-handling proteins, in particular the SR Ca(2+)-ATPase (SERCA2a), are thought to cause an overall reduction in the amount of SR-Ca(2+) available for contraction. In the steady state, the Ca(2+)-content of the SR is essentially a balance between Ca(2+)-uptake via SERCA2a pump and Ca(2+)-release via the cardiac SR Ca(2+)-release channel complex (Ryanodine receptor, RyR2). This review discusses current pharmacological options available to enhance cardiac SR Ca(2+) content and the implications of this approach as an inotropic therapy in heart failure. Two options are considered: (i) activation of the SERCA2a pump to increase SR Ca(2+)-uptake, and (ii) reduction of SR Ca(2+)-leakage through RyR2. RyR2 forms a macromolecular complex with a number of regulatory proteins that either remain permanently bound or that interact in a time- and/or Ca(2+)-dependant manner. These regulatory proteins can dramatically affect RyR2 function, e.g. over-expression of the accessory protein FK 506-binding protein 12.6 (FKBP12.6) has recently been shown to reduce SR Ca(2+)-leak. Recent attempts to design positive inotropes for chronic administrations have focussed on the use of phosphodiesterase III inhibitors (PDE III inhibitors). These compounds, which increase intracellular cAMP-levels, have failed in clinical trials. Therefore medical researchers are seeking new drugs that act through alternative pathways. Novel cardiac inotropes targeting SR Ca(2+)-cycling proteins may have the potential to fill this gap.
Increasing Access to Kidney Transplantation: Easy as A-B-O.

2016 by the National Kidney Foundation, Inc. All rights reserved. 1548-5595/$36.00 http://dx.doi. org/10.1053/j.ackd. 2016.08. 001 T issue of Advances in Chronic Kidney Disease is focused on kidney transplantation. It is shepherded by Drs Anita Patel and Millie Samaniego-Picota who have produced, with their selected group of authors, a contemporaneous and coherent view of kidney allograft survival. In discretely dissected steps, the authors have delineated their thoughts regarding their issue’s theme, and the readers will undoubtedly pivot their viewpoint. This brief treatise has the same intent to convince one that ABO-incompatible (ABOi) kidney transplantation is compatible with one’s current practice of kidney transplantation. There are 4 major Landsteiner blood groups: A, B, AB, and O. These polysaccharide immunogens are expressed on multiple tissues including erythrocytes, platelets, and endothelial cells and generate hemagglutinating immunoglobulins of the immunoglobulin (Ig) M and IgG types, with the latter pathogenic in kidney transplant rejection. Blood group A has subtypes A1 and A2, the latter of which is less immunogenic, thereby facilitating transplantation of A2 kidneys to ABOi donors. Transfusion of an incompatible blood group to a recipient can be devastating with resulting hemolysis, acute kidney injury, and even death. Transfusion of compatible blood group red cells can produce allosensitization; however, this issue is possibly exaggerated. Even after essentially the Food and Drug Administration mandated reductions in erythropoiesis-stimulating agent use, there has not been a substantial increase in allosensitization despite an absolute increase in transfusion event rates per patient after 2011. Renal transplantation among the 4 blood groups yields a 43 4 matrix with 16 possible donor-recipient blood group combinations (Table 1). Immediately, one recognizes the challenge of 7 ABOi donor-recipient combinations and 9 ABO-compatible (ABOc) donor-recipient combinations that are eminently feasible. Outcomes for ABOc donorrecipient combinations are startlingly successful. Oneyear patient and allograft survival achievement thresholds are established by the United Network for Organ Sharing and aspirational. Fulfillment of these goals by most transplant centers requires diligence and vigilance
Lack of Effect of Prophylactic N-acetylcysteine on Postoperative Organ Dysfunction following Major Abdominal Tumour Surgery: A Randomized, Placebo-controlled, Double-blinded Clinical Trial

Sepsis and respiratory dysfunction leading to multiple system organ failure remains the leading cause of postoperative morbidity and mortality following major surgical procedures. It has been suggested the oxygen free radicals might play a pivotal role in this process. The aim of this study was to investigate whether short-term infusion of N-acetylcysteine (N-acetylcysteine), a potent antioxidant, administered before and during extensive abdominal surgery, could ameliorate the progression of early postoperative organ dysfunction and improve oxygenation. Out of the 93 patients, 47 received N-acetylcysteine and 46 were given placebo in a randomized, controlled, double-blinded fashion. Patients received N-acetylcysteine (150 mg.kg -1 bolus followed by a continuous infusion of 12 mg.kg -1 .h -1 ) or the same volume of placebo (5% dextrose) during surgery. Treatment effect on organ function was assessed by organ dysfunction scores according to physiological parameters of six main organ systems: respiratory, cardiovascular, renal, hepatic, haematological and central nervous system. The scores were obtained on admission, then daily during the first three postoperative days. For statistical analysis Mann-Whitney U and Chi-squared tests were used. There was no significant difference between the two groups in any of the six organ dysfunction parameters, length of intensive care stay, days of mechanical ventilation and mortality. Our results do not support the routine use of N-acetylcysteine as a prophylactic measure during surgery, and reinforce previous evidence which challenges the indication of N-acetylcysteine in the critically ill.
The Development and Empirical Validation of Strategic Decision Models

Strategic management emerged in the last decade as a leading factor in advancing managerial capabilities. A major reason for its having achieved this status is that it focuses attention on making decisions that (i) are consistent with whatever reliable information is available at the time a particular decision has to be made, and (2) position the company most effectively, offensively as well as defensively, to meet future challenges of the environment. Significant contributions to study of strategic management have come from numerous researchers employing a multiplicity of analytical methods. Harrigan [1] presents an excellent survey of these contributions and their relationships with one another. Much of this research has been directed toward explaining the process by which strategy is formulated. To shift the orientation and focus more to the content of strategy, Harrigan advocates what she refers to as a hybrid methodology that combines the great contextual detail of case studies with the statistical rigor
Gene–environment interactions influence ecological consequences of transgenic animals

Production of transgenic animals has raised concern regarding their potential ecological impact should they escape or be released to the natural environment. This concern has arisen mainly from research on laboratory-reared animals and theoretical modeling exercises. In this study, we used biocontained naturalized stream environments and conventional hatchery environments to show that differences in phenotype between transgenic and wild genotypes depend on rearing conditions and, critically, that such genotype-by-environment interactions may influence subsequent ecological effects in nature. Genetically wild and growth hormone transgenic coho salmon (Oncorhynchus kisutch) were reared from the fry stage under either standard hatchery conditions or under naturalized stream conditions. When reared under standard hatchery conditions, the transgenic fish grew almost three times longer than wild conspecifics and had (under simulated natural conditions) stronger predation effects on prey than wild genotypes (even after compensation for size differences). In contrast, when fish were reared under naturalized stream conditions, transgenic fish were only 20% longer than the wild fish, and the magnitude of difference in relative predation effects was much reduced. These data show that genotype-by-environment interactions can influence the relative phenotype of transgenic and wild-type organisms and that extrapolations of ecological consequences from phenotypes developed in the unnatural laboratory environment may lead to an overestimation or underestimation of ecological risk. Thus, for transgenic organisms that may not be released to nature, the establishment of a range of highly naturalized environments will be critical for acquiring reliable experimental data to be used in risk assessments.
Role of Neuropeptide Y and Galanin in High Altitude Induced Anorexia in Rats

Anorexia causing weight loss at high altitude (HA) is a major problem. Neuropeptide Y (NPY) and galanin are considered to have appetite regulatory function. The present study was therefore undertaken to investigate the changes in these two peptides at simulated HA and its possible role in anorexia. Male Sprague-Dawley rats (n = 8 in each group) were exposed to simulated HA (7620 m) for 1, 7, 14 and 21 days for 6h a day and to an altitude of 6096 m for 72h to study the effect of intermittent and continuous exposure, respectively. NPY and galanin levels were estimated in different brain parts and plasma of exposed and unexposed control animals. Significant reduction in food intake was observed in rats during both intermittent as well as continuous exposure. In case of 72h continuous exposure severe reduction in food intake was observed (73.2%) with reduction in body mass (∼29.7 g/rat in 48h). Hypothalamic NPY levels were decreased by 54.7, 35.0 and 15.4% in 1, 7, and 14 days, respectively, in case of intermittent exposure to HA. However in case of 72 h HA exposure no significant change in hypothalamic and circulating NPY levels were observed. Plasma galanin levels were decreased in both intermittent and 72h continuous HA exposed rats. Hypothalamic galanin levels were also decreased in 72h exposed rats. The changes in levels of these peptides may be responsible for anorexia at HA.
Alcohol Intoxication Among Dutch Adolescents: Acute Medical Complications in the Years 2000-2010

Objective: To investigate acute medical complications of alcohol intoxication among adolescents presenting to Reinier de Graaf Hospital, a major nonacademic hospital in Delft, the Netherlands. Methods: The frequency of reduced consciousness, hypothermia, electrolyte disturbances, hypoglycemia, and acidosis along with alcohol intoxication was retrospectively studied in the medical records of patients aged 11 to 17 years admitted between January 1, 2000, and April 30, 2010. Results: Reduced consciousness (45%) and hypothermia (43.1%) were the most common clinical findings. More boys than girls experienced hypothermia (P = .028), probably because of the higher blood alcohol concentration level ( P = .026), which was associated with lower temperature (Pearson’s r = -.37; P < .001). The most frequent electrolyte disturbance was hyperchloremia (31.1%), followed by low bicarbonate (22%), hypokalemia (11.9%), and hypernatremia (7.7%). Strikingly, none of the patients in this study suffered hypoglycemia. On the contrary, 13.6% of the patients were slightly hyperglycemic. Mild acidosis, both metabolic and respiratory, was observed among 28.8% of the patients, although the metabolic component predominated. Conclusions: Acute medical complications because of alcohol intoxication appeared to be mild, and most remarkably none of the patients experienced hypoglycemia.
The Challenges of Advancing Fiscal Equity in a Resource-Strained Context

Weighted student funding (WSF) is a multifaceted school finance, management, and governance reform that is gaining attention. While WSF has a number of goals, its primary objective is to redress intra-district funding inequities. This article draws on a mixed-methods study of WSF in Prince George’s County Public Schools to examine the initiative’s impact on the distribution of financial resources to the 180 schools that were affected by it. Our findings indicate that WSF was not a robust mechanism for advancing equity and illustrate how technical, economic, and political factors can undermine the ability of WSF to realize its equity goals.
Activation of alpha-1A adrenoceptors mobilizes calcium from the intracellular stores in myocytes from rat portal vein.

Intracellular free Ca++ concentration ([Ca++]i) was monitored using the fluorescence from the dye fura-2-acetoxymethylester in single myocytes from rat portal vein. In the presence of oxodipine (a L-type Ca++ channel inhibitor), norepinephrine (10 microM) evoked transient increases in [Ca++]i which were related to release of Ca++ from intracellular stores. The alpha-1 adrenoceptors mediating intracellular Ca++ release and inositol phosphate accumulation were identified by using subtype-selective agonists and antagonists. Pretreatment with chloroethylclonidine had little effect on the norepinephrine-induced increase in [Ca++]i and inositol phosphate accumulation. In contrast, prazosin, 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane and alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino )- propyl)benzeneacetonitrile fumarate produced a concentration-dependent inhibition of both intracellular Ca++ release and inositol phosphate accumulation. The rank of potency was prazosin > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane > alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino - propyl) benzeneacetonitrile fumarate. Methoxamine was as effective as norepinephrine but was less potent as shown by the rightward shift of the concentration-response curves. These results indicate that myocytes from rat portal vein express alpha-1A adrenoceptors whose activation stimulates phosphoinositide turnover and release of Ca++ from intracellular stores. The alpha-1A adrenoceptor stimulation of [Ca++]i and subsequent activation of Ca(++)-activated Cl- current was insensitive to intracellular applications of pertussis toxin, but concentration-dependently blocked by intracellular dialysis with a pipette solution containing anti-alpha q/alpha 11 antibody (whole cell recording mode). (ABSTRACT TRUNCATED AT 400 WORDS)
Spectrum of pediatric brain tumors in India: a multi-institutional study.

BACKGROUND Till date there is no published multi-institutional data regarding the epidemiological profile of pediatric brain tumors in India. AIM The present retrospective study analyses the histological spectrum of pediatric age group brain tumors in seven tertiary care hospitals in India. MATERIAL AND METHODS Data regarding frequencies of various primary brain tumors (diagnosed according to the World Health Organization (WHO) classification), in 3936 pediatric patients (<18 yrs of age), was collected from seven tertiary care hospitals in India. RESULTS The most common primary pediatric brain tumors were astrocytic tumors (34.7%), followed by medulloblastoma and supratentorial primitive neuro-ectodermal tumors (22.4%), craniopharyngiomas (10.2%) and ependymal tumors (9.8%). The most common astrocytic tumor was pilocytic astrocytoma. In comparison to adults, oligodendrogliomas and lymphomas were rare in children. CONCLUSIONS Our study is the first such report on the histological spectrum of brain tumors in children in India. Except for a slightly higher frequency of craniopharyngiomas, the histological profile of pediatric brain tumors in India is similar to that reported in the Western literature.
Prevalence of Depression and Depressive Symptoms Among Resident Physicians: A Systematic Review and Meta-analysis.

IMPORTANCE Physicians in training are at high risk for depression. However, the estimated prevalence of this disorder varies substantially between studies. OBJECTIVE To provide a summary estimate of depression or depressive symptom prevalence among resident physicians. DATA SOURCES AND STUDY SELECTION Systematic search of EMBASE, ERIC, MEDLINE, and PsycINFO for studies with information on the prevalence of depression or depressive symptoms among resident physicians published between January 1963 and September 2015. Studies were eligible for inclusion if they were published in the peer-reviewed literature and used a validated method to assess for depression or depressive symptoms. DATA EXTRACTION AND SYNTHESIS Information on study characteristics and depression or depressive symptom prevalence was extracted independently by 2 trained investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. MAIN OUTCOMES AND MEASURES Point or period prevalence of depression or depressive symptoms as assessed by structured interview or validated questionnaire. RESULTS Data were extracted from 31 cross-sectional studies (9447 individuals) and 23 longitudinal studies (8113 individuals). Three studies used clinical interviews and 51 used self-report instruments. The overall pooled prevalence of depression or depressive symptoms was 28.8% (4969/17,560 individuals, 95% CI, 25.3%-32.5%), with high between-study heterogeneity (Q = 1247, τ2 = 0.39, I2 = 95.8%, P < .001). Prevalence estimates ranged from 20.9% for the 9-item Patient Health Questionnaire with a cutoff of 10 or more (741/3577 individuals, 95% CI, 17.5%-24.7%, Q = 14.4, τ2 = 0.04, I2 = 79.2%) to 43.2% for the 2-item PRIME-MD (1349/2891 individuals, 95% CI, 37.6%-49.0%, Q = 45.6, τ2 = 0.09, I2 = 84.6%). There was an increased prevalence with increasing calendar year (slope = 0.5% increase per year, adjusted for assessment modality; 95% CI, 0.03%-0.9%, P = .04). In a secondary analysis of 7 longitudinal studies, the median absolute increase in depressive symptoms with the onset of residency training was 15.8% (range, 0.3%-26.3%; relative risk, 4.5). No statistically significant differences were observed between cross-sectional vs longitudinal studies, studies of only interns vs only upper-level residents, or studies of nonsurgical vs both nonsurgical and surgical residents. CONCLUSIONS AND RELEVANCE In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among resident physicians was 28.8%, ranging from 20.9% to 43.2% depending on the instrument used, and increased with calendar year. Further research is needed to identify effective strategies for preventing and treating depression among physicians in training.
Decreased metabolic response to visual stimulation in the superior colliculus of mice lacking the glial glutamate transporter GLT‐1

During a specific task, an increase in glucose utilization anatomically restricted to the functionally activated region(s) is a landmark of brain physiology. While this response represents the biological bases for functional brain imaging, the underlying signalling pathway(s) are still not fully characterized. Recent evidence suggests that glial glutamate (re)uptake plays a key role. We provide evidence that the metabolic response to synaptic activation (i.e. enhancement of glucose uptake) is decreased in the superior colliculus during visual stimulation in young adult mice deficient in the glial glutamate transporter GLT‐1. A similar reduction was not observed in the glial glutamate transporter GLAST‐knockout mice. Consistent with our previous observation obtained in the somatosensory cortex, our data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the adult brain which would be regulated by synaptic activity and mediated by GLT‐1.
Performance Evaluation and Comparison and Improvement of Standard Cell Placement Techniques in VLSI Design

Heuristic approach is preferred as a solution to optimization of Non-Deterministic Polynomial hard (NP-hard) problems of sizes that are nontrivial because of speed limitations of exact optimization methods. This paper, therefore, proposes to investigate recent heuristic techniques for solving the standard cell placement problems at physical design stage of VLSI design cycle. The techniques considered are Simulated Annealing (SA), Hopfield Neural Network and Genetic Algorithm (GA). In addition to individual studies of the methods, we compare them in terms of solution quality and computing speed in connection with the standard cell placement problems. Finally we shall suggest a method to enhance them using Memetic Algorithms (MA).
An Initial Investigation of Do Not Resuscitate Acceptance in Egypt

Background: The aim of this work was to obtain objective data on the extent of knowledge and attitudes of the do not resuscitate (DNR) concept in an Egyptian urban setting. Methods: This survey was conducted in Cairo, Egypt, using a structured questionnaire including 23 questions. Questions and questionnaire were developed from literature on DNR in the region and from pilot testing. Results: A total of 461 persons participated. In all, 48 participants (10.4%, 95% confidence interval [CI]: 7.8-13.7) agreed on the concept of DNR, 226 (49%, 95% CI: 36.1-45.2) stated that it depends on the patient condition, and 187 (40.5%, 95% CI: 44.4-53.7) rejected DNR. Combining the first 2 categories, agree and depends on patient condition, over 60% of the respondents in effect supported DNR. Family members (35.6%, 95% CI: 31.4-40.3) and attending physicians (43.3%, 95% CI: 30.1-39.0) were selected over religious leaders (21%, 95% CI: 17.5-25.2) and representatives from state institutions (4.6%, 95% CI: 2.9-7.0) as to who should have authority for making a DNR decisions. Discussion: These and additional results provide objective evidence that DNR will not be rejected outright in Egypt. More formal surveys are justified and will provide needed guidance for implementing DNR and related end-of-life medical care in Egypt.