Miracle-dz/UniFAR-FTUs huggingface dataset:
Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CA1 region of rat hippocampal slices (11‐30 days) were studied using extracellular and whole‐cell patch‐clamp recording techniques. 2. Trans‐1‐amino‐1,3‐cyclopentanedicarboxylic acid (trans‐ACPD; 25‐100 microM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential. 3. Ibotenate (25 microM) or L‐glutamate (250 microM), in the presence of the N‐methyl‐D‐aspartate (NMDA) receptor antagonist, D‐2‐amino‐5‐phosphonovaleric acid (APV, 50‐75 microM), depressed the EPSC amplitude while inducing no detectable inward current. L‐2‐Amino‐4‐phosphonobutyrate (L‐AP4, 25‐100 microM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current. 4. The NMDA receptor‐mediated component of the EPSC recorded in the presence of the non‐NMDA receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 20‐30 microM) was depressed by trans‐ACPD, L‐AP4, or quisqualate (1‐2 microM). 5. The response to ionophoretic application of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) was unaffected by trans‐ACPD or L‐AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired‐pulse facilitation (50‐75 ms interstimulus interval) was reversibly enhanced by trans‐ACPD or L‐AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic ‘autoreceptor’. 6. The effects of trans‐ACPD or L‐AP4 on synaptic transmission decreased significantly over ages 12‐30 days and were minimal in adult (greater than 80 days) slices. 7. The depression of synaptic transmission caused by trans‐ACPD or L‐AP4 was not altered following the induction of long‐term potentiation (LTP). 8. The results indicate that metabotropic glutamate receptor agonists suppress excitatory synaptic transmission in CA1 pyramidal cells by an action at a presynaptic site. This effect is developmentally regulated and is maximally expressed during the first postnatal month.
The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity

1 The effects of acute and subchronic nicotine and (+)‐amphetamine on the extracellular levels of dopamine and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens (NAc) have been studied in conscious, freely‐moving rats by use of in vivo microdialysis. 2 In rats which had been habituated to the test apparatus for approximately 80 min, the acute subcutaneous (s.c.) administration of nicotine (0.1 or 0.4 mg kg−1) caused a dose‐dependent increase (P < 0.01) in spontaneous activity and evoked significant increases (P < 0.05) in the extracellular levels of DOPAC and HVA. 3 Measurements made 24 h after the last injection of nicotine showed that pretreatment with the higher doses tested (0.4 mg kg−1) resulted in increased basal levels of dopamine (P < 0.01) and decreased basal levels of DOPAC (P < 0.05) in the NAc dialysates. 4 Pretreatment with nicotine (0.1 or 0.4 mg kg−1 daily for 5 days) enhanced the effects of the drug on spontaneous locomotor activity and enhanced the effects of the drug on extracellular levels of dopamine to the extent that the response became significant (P < 0.05). 5 If a dopamine uptake inhibitor, nomifensine, was added to the Ringer solution used to dialyse the probe, the s.c. administration of both acute and subchronic nicotine (0.4 mg kg−1) resulted in significant increases (P < 0.05) in the dopamine concentration in the dialysate. Under these conditions, pretreatment with nicotine prior to the test day prolonged (P < 0.05) the dopamine response to a challenge dose of nicotine. 6 Subcutaneous injections of (+)‐amphetamine (0.2 or 0.5 mg kg−1) evoked dose‐dependent increases in both spontaneous activity and the concentration of dopamine in NAc dialysates. These responses were unaffected by 5 days pretreatment with the drug. 7 The results of this study support the conclusion that the enhanced locomotor response to nicotine observed in animals pretreated with the drug prior to the test day is associated with potentiation of its effects on dopamine secretion in the NAc.
The effect of the menstrual cycle on asthma presentations in the emergency department.

BACKGROUND Seventy-five percent of all adult hospital admissions for asthma are women. OBJECTIVE To determine whether a relationship exists between phases of the menstrual cycle and asthma exacerbations in adult females. METHODS Data were analyzed from 182 nonpregnant, adult females with asthma aged 13 years to menopause. Date of presentation, patient age, duration of asthma attack, date of last menstrual period, regular interval between menses, presenting peak expiratory flow rate, and admission and discharge decision were recorded prospectively. Treatment interventions abstracted retrospectively from patient charts included use of oxygen, xanthines, beta-adrenergic agonists, corticosteroids, and magnesium sulfate. The menstrual cycle was divided into 4 phases based on fluctuations in serum estradiol levels. The 4 intervals were preovulatory (days 5-11), periovulatory (days 12-18), postovulatory (days 19-25), and perimenstrual (days 26-4). RESULTS Data were analyzed with a goodness-of-fit chi 2. Between June 1991 and May 1992, 182 females (mean +/- SD age, 28.5 +/- 8.0 years) were surveyed. No significant differences were noted for use of oxygen, beta-adrenergic agonists, xanthines, or magnesium among members of the 4 menstrual groups. Intervention with corticosteroids was least in the postovulatory interval (y:n) 0.5:1 and greatest in the preovulatory interval 3.0:1 (alpha = .03) Presentations by menstrual interval were as follows: preovulatory, 36 (20%); periovulatory, 43 (24%); postovulatory, 18 (10%); and perimenstrual, 85 (46%) (alpha < .01). CONCLUSIONS Asthma presentations are least frequent when serum estradiol levels are at a sustained peak. We observed a 4-fold variation in asthma presentations during the perimenstrual interval, when serum estradiol levels decrease sharply after that prolonged peak. These findings suggest that monthly variations in serum estradiol levels may influence the severity of asthma in adult females.
Presubiculum layer III conveys retrosplenial input to the medial entorhinal cortex

Navigation is mediated by a network of brain areas, and research has focused on the head‐direction system in the presubiculum (PrS), the grid cell containing medial entorhinal cortex (EC) (MEC) and place cells in the hippocampus. Less research addressed the interactions of the retrosplenial cortex (RSC) and the navigational system, although it is well established that damage to the RSC leads to navigational deficits. We previously showed that RSC provides a dense input to deep layers of MEC and to superficial layers of PrS. In this study we use confocal microscopical analysis and show that the dense projection from the caudal part of the ventral retrosplenial granular cortex targets neurons in Layer III of PrS, which provide input to superficial layers of MEC. Our high resolution anatomical data indicate that sparsely spiny pyramidal neurons in Layer III of PrS that originate projections to Layer III of MEC are the main target of these retrosplenial projections. Retrosplenial axonal boutons were found to equally contact spines and shafts of basal dendrites in Layer III, but contacts on shafts are more prominent close to the soma, indicating the potential for efficient synaptic transfer. These observations suggest that neurons in Layer III of PrS have an important role in mediating RSC contributions to navigation. © 2011 Wiley‐Liss, Inc
The impact of the electronic medical record on structure, process, and outcomes within primary care: a systematic review of the evidence

BACKGROUND The electronic medical record (EMR)/electronic health record (EHR) is becoming an integral component of many primary-care outpatient practices. Before implementing an EMR/EHR system, primary-care practices should have an understanding of the potential benefits and limitations. OBJECTIVE The objective of this study was to systematically review the recent literature around the impact of the EMR/EHR within primary-care outpatient practices. MATERIALS AND METHODS Searches of Medline, EMBASE, CINAHL, ABI Inform, and Cochrane Library were conducted to identify articles published between January 1998 and January 2010. The gray literature and reference lists of included articles were also searched. 30 studies met inclusion criteria. RESULTS AND DISCUSSION The EMR/EHR appears to have structural and process benefits, but the impact on clinical outcomes is less clear. Using Donabedian's framework, five articles focused on the impact on healthcare structure, 21 explored healthcare process issues, and four focused on health-related outcomes.
Peroxidase‐mediated degradation of perfluorooctanoic acid

Concentrations of aqueous‐phase perfluorooctanoic acid (PFOA), a representative perfluorinated aliphatic (PFA) compound, are shown to be reduced effectively via reaction with horseradish peroxidase (HRP), hydrogen peroxide, and a phenolic cosubstrate (4‐methoxyphenol). Reaction rate profiles are pseudo–first order, yielding an apparent best‐fit removal rate constant of k1 = 0.003/min (r2 = 0.96, n = 14). Approximately 68% depletion of the parent compound and 98% depletion of its related acute aquatic toxicity are achieved in 6 h. Because no PFOA removal is observed in the absence of cosubstrate and/or following consumption thereof, we conclude that radical intermediate species generated during reaction between HRP and 4‐methoxyphenol mediate nonspecific depletion of PFOA and that these intermediates may be sufficiently reactive to sever the extremely stable C–F bonds of PFOA. These results are consistent with measurements of reaction by‐products, including fluoride ion and various aliphatic species of shortened chain length. Based on these findings, we conclude that PFA degradation may occur via one of two mechanisms: Kolbe decarboxylation followed by stepwise conversion of–CF2 units to CO2 and fluoride ion, or radical abstraction from a double bond with subsequent fragmentation. Our results indicate that under appropriate conditions, enzymatic degradation may comprise a natural transformation pathway for PFAs. Moreover, we anticipate that appropriately engineered enzymatic processes may hold promise for treatment of PFOA‐contaminated waters. This, to the best of our knowledge, is the first report to substantiate the efficacy of HRP‐catalyzed reactions for contaminant removal via degradative reactions versus polymerization reactions.
Time to platelet recovery predicts outcome of patients with de novo acute lymphoblastic leukaemia who have achieved a complete remission

Summary. Survival in acute leukaemia depends on the achievement of complete remission (CR). However, CR is not a clear‐cut phenomenon and certain variables of its definition could more accurately characterize the quality of the remission. Because platelet recovery > 100 × 109/l is an essential component of CR in acute leukaemia, we hypothesized that time to platelet recovery (TPR) might be predictive of overall survival (OS) or disease‐free survival (DFS) in acute lymphoblastic leukaemia (ALL). We analysed TPR in 249 patients with ALL who entered CR after one course of induction chemotherapy and correlated TPR with DFS and OS. TPR was significantly associated with both DFS and OS if it occurred within a maximum of about 60 d from start of therapy. Furthermore, during that time period, the relative risk of death increased with increasing TPR. Although presence of the Philadelphia chromosome was the single most important adverse feature at diagnosis, the effect of TPR on survival continued to be significant within this patient subgroup. This effect was so pronounced that Philadelphia chromosome‐positive patients with a TPR of 12 d had a better outcome than Philadelphia chromosome‐negative patients with a TPR of 48 d. Thus, a short TPR seems to be able to override adverse characteristics in the outcome of ALL patients treated with chemotherapy. We conclude that a quicker TPR predicts longer DFS and OS in patients with ALL. As platelet counts are obtained almost daily in patients undergoing chemotherapy, TPR can readily be utilized to assess the prognosis of these patients.
Geographic Variation in End‐Stage Renal Disease Incidence and Access to Deceased Donor Kidney Transplantation

The effect of demand for kidney transplantation, measured by end‐stage renal disease (ESRD) incidence, on access to transplantation is unknown. Using data from the U.S. Census Bureau, Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) from 2000 to 2008, we performed donation service area (DSA) and patient‐level regression analyses to assess the effect of ESRD incidence on access to the kidney waiting list and deceased donor kidney transplantation. In DSAs, ESRD incidence increased with greater density of high ESRD incidence racial groups (African Americans and Native Americans). Wait‐list and transplant rates were relatively lower in high ESRD incidence DSAs, but wait‐list rates were not drastically affected by ESRD incidence at the patient level. Compared to low ESRD areas, high ESRD areas were associated with lower adjusted transplant rates among all ESRD patients (RR 0.68, 95% CI 0.66–0.70). Patients living in medium and high ESRD areas had lower transplant rates from the waiting list compared to those in low ESRD areas (medium: RR 0.68, 95% CI 0.66–0.69; high: RR 0.63, 95% CI 0.61–0.65). Geographic variation in access to kidney transplant is in part mediated by local ESRD incidence, which has implications for allocation policy development.
Bias in random regret models due to measurement error: formal and empirical comparison with random utility model

ABSTRACT This study addresses the so-called uncertainty problem due to measurement error in random utility and random regret choice models. Based on formal analysis and empirical comparison, we provide new insights about the uncertainty problem in discrete choice modeling. First, we formally show how measurement error affects the random regret model differently from the random utility model. Then, random measurement error is introduced into level-of-service variables and the effect of measurement error is analyzed by comparing the estimated parameters of the concerned choice models, before and after introducing measurement error. We argue that although measurement error leads to biased estimation results in both types of models, uncertainty tends to accumulate in random regret models because this model involves a comparison of alternatives. Therefore, input uncertainty tends to lead to larger bias in random regret models. Moreover, since random regret models assume semi-compensatory decision processes, bias in random utility models is homogenous across individuals and alternatives, while bias in random regret models is heterogeneous. Several approaches are discussed to overcome this uncertainty problem in random regret models.
Is there a role for day‐to‐day home blood pressure variability in guiding management of hypertension?

Although two population‐based studies have demonstrated the prognostic value of day‐to‐day home blood pressure (BP) variability, data are still limited. Thresholds of normality, target levels for treatment and optimal number and times of home measurement needed for better assessment of day‐to‐day home BP variability also remain to be investigated. Although further prospective studies are required, home BP is a strong and modifiable risk factor, and patient compliance should be encouraged.
Branching, lending and competition in Italian banking

ABSTRACT With the liberalization of legal barriers to the opening of bank branches in 1990, both market structure and competitive conditions in Italy changed profoundly as banks expanded their branching networks. This paper provides novel empirical evidence on how changes of the branch network structure at the province level affect the performance and lending activity of banks across the period 1993–2011. In particular, we adopt two modes of analysis. The first focuses on the impact of diversification strategies on performance, lending and funding strategies at the province level. The second one examines how the increase of big banks' local presence affects single-market bank performance and lending strategies. Our results show that geographical diversification strategies can reduce performance, the adjusted Lerner Index of banks and lending activities, but increase the Lerner Index in deposit markets. Furthermore, we find that the expansion of branches by large-medium sized banks in concentrated markets can reduce the Lerner Index for the deposit market and the amount of loans offered by single-market banks.
Use of cyclosporin in the treatment of steroid resistant post-keratoplasty atopic sclerokeratitis

AIMS To demonstrate that oral cyclosporin is successful in the management of steroid refractory post-keratoplasty atopic sclerokeratitis (PKAS). METHODS Series of three patients. RESULTS The patients developed PKAS between 2 and 11 days after surgery. All cases failed to respond to oral prednisolone 60–80 mg daily for 10–30 days but resolved with the addition of systemic cyclosporin 5.0–7.5 mg/kg/day. There have been no relapses following withdrawal of therapy after 3–18 months. CONCLUSIONS PKAS is an uncommon, but severe, complication of corneal graft surgery and often responds to oral prednisolone treatment. Oral cyclosporin results in rapid resolution of PKAS in steroid unresponsive cases.
ser31 tyrosine hydroxylase phosphorylation parallels differences in dopamine recovery in nigrostriatal pathway following 6‐OHDA lesion

Compensatory mechanisms in dopamine (DA) signaling have long been proposed to delay onset of locomotor symptoms during Parkinson's disease progression until ~ 80% loss of striatal DA occurs. Increased striatal dopamine turnover has been proposed to be a part of this compensatory response, but may occur after locomotor symptoms. Increased tyrosine hydroxylase (TH) activity has also been proposed as a mechanism, but the impact of TH protein loss upon site‐specific TH phosphorylation in conjunction with the impact on DA tissue content is not known. The tissue content of DA was determined against TH protein loss in the striatum and substantia nigra (SN) following 6‐hydroxydopamine lesion in the medial forebrain bundle in young Sprague–Dawley male rats. Although DA predictably decreased in both regions following 6‐hydroxydopamine, there was a significant difference in DA loss between the striatum (75%) and SN (40%), despite similar TH protein loss. Paradoxically, there was a significant decrease in DA against remaining TH protein in striatum, but a significant increase in DA against remaining TH in SN. In the SN, increased DA per remaining TH protein was matched by increased ser31, but not ser40, TH phosphorylation. In striatum, both ser31 and ser40 phosphorylation decreased, reflecting decreased DA per TH. However, in control nigral and striatal tissue, only ser31 phosphorylation correlated with DA per TH protein. Combined, these results suggest that the phosphorylation of ser31 in the SN may be a mechanism to increase DA biosynthesis against TH protein loss in an in vivo model of Parkinson's disease.
Distribution of glucagonlike peptide I (GLP‐I), glucagon, and glicentin in the rat brain: An immunocytochemical study

Although glucagonlike immunoreactants (GLIs) are present in the central nervous system of several mammalian species, their structural relationship with pancreatic proglucagon is not defined, and their precise anatomical distribution has not been studied extensively. To obtain further information about the structure and biological significance of brain GLIs, the anatomical distribution of three different antigenic determinants of pancreatic proglucagon‐‐glucagonlike peptide I (GLP‐I), glucagon, and glicentin‐‐was mapped in the brain of colchicine‐treated rats by immunocytochemistry using the avidin‐biotin‐peroxidase method.
[NMR-spectroscopy-based metabonomic approach to analysis of Siwutang, a novel prescription, treated blood deficiency in mice].

OBJECTIVE To discover the characteristic changes of metabolic profiles in C57 mice with cyclophosphamide induced blood deficiency and the effect of Siwutang. METHOD An integrated metabonomic study using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy has been applied to investigate the metabolic profiles of serum, aqueous and lipidic extracts of thoracic gland, spleen, bone marrow obtained from control, model group (intraperitoneal injection of cyclophosphamide at a dose of 250 mg x kg(-1)) and Siwutang treated model group. The NMR spectra were integrated in segments of 0.04 ppm and then analyzed by principal component analysis (PCA) using SIMCA-P software to visualize the similarities and differences in metabolic profiles between these groups. RESULT PCA result showed conspicuous difference in the metabolic profiles between groups. Compared with the control group, the model group contained lower concentration of lactate, 3-hydroxybutyrate, choline, glucose, and higher concentration of VLDL/LDL, leucine/isoleucine in serum. Lower concentration of taurine choline, Fbeta:RCH2CH2CO, Epi-coprostanol and lactate were found in both in thoracic gland extracts and spleen extracts. And in spleen extracts, we also found the lower concentration of 3-HB. In the extracts of bone marrow, the lower concentration of lactate, choline, glucosee were observed. When they were dosed with Siwutang 10 g x kg(-1) x d(-1) for 7 days, the effects above-mentioned were reversed. CONCLUSION The injury established by injecting CTX is a kind of proper model to develop further metabonomics researches. The damage of mitochondria, disorder of energy metabolism and osmoregulation are observed in cyclophosphamide caused blood deficiency model by NMR-based-metabonomics method, and the Siwutang can improve these effects.
Towards the Control of Individual Fingers of a Prosthetic Hand Using Surface EMG Signals

The fast pace of development of upper-limb prostheses requires a paradigm shift in EMG-based controls. Traditional control schemes are only capable of providing 2 degrees of freedom, which is insufficient for dexterous control of individual fingers. We present a framework where myoelectric signals from natural hand and finger movements can be decoded with a high accuracy. 32 surface-EMG electrodes were placed on the forearm of an able-bodied subject while performing individual finger movements. Using time-domain feature extraction methods as inputs to a neural network classifier, we show that 12 individuated flexion and extension movements of the fingers can be decoded with an accuracy higher than 98%. To our knowledge, this is the first instance in which such movements have been successfully decoded using surface-EMG. These preliminary findings provide a framework that will allow the results to be extended to non-invasive control of the next generation of upper-limb prostheses for amputees.