Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of the antianginal drug, ranolazine, on the brain sodium channel NaV1.2 and its modulation by extracellular protons

Ranolazine is an antianginal drug currently approved for treatment of angina pectoris in the United States. Recent studies have focused on its effects on neuronal channels and its possible therapeutic uses in the nervous system. We characterized how ranolazine affects the brain sodium channel, NaV1.2, and how its actions are modulated by low pH. In this way, we further explore ranolazine's potential as an anticonvulsant and its efficacy in conditions like those during an ischaemic stroke.
Secondary Analysis of an Electronic Surveillance System Combined with Multi-focal Interventions for Early Detection of Sepsis

Summary Summary: To conduct an independent secondary analysis of a multi-focal intervention for early detection of sepsis that included implementation of change management strategies, electronic surveil-lance for sepsis, and evidence based point of care alerting using the POC AdvisorTM application. Methods: Propensity score matching was used to select subsets of the cohorts with balanced covariates. Bootstrapping was performed to build distributions of the measured difference in rates/ means. The effect of the sepsis intervention was evaluated for all patients, and High and Low Risk subgroups for illness severity. A separate analysis was performed patients on the intervention and non-intervention units (without the electronic surveillance). Sensitivity, specificity, and the positive predictive values were calculated to evaluate the accuracy of the alerting system for detecting sepsis or severe sepsis/ septic shock. Results: There was positive effect on the intervention units with sepsis electronic surveillance with an adjusted mortality rate of –6.6%. Mortality rates for non-intervention units also improved, but at a lower rate of –2.9%. Additional outcomes improved for patients on both intervention and non-intervention units for home discharge (7.5% vs 1.1%), total length of hospital stay (-0.9% vs –0.3%), and 30 day readmissions (-6.6% vs –1.6%). Patients on the intervention units showed better outcomes compared with non-intervention unit patients, and even more so for High Risk patients. The sensitivity was 95.2%, specificity of 82.0% and PPV of 50.6% for the electronic surveillance alerts. Conclusion: There was improvement over time across the hospital for patients on the intervention and non-intervention units with more improvement for sicker patients. Patients on intervention units with electronic surveillance have better outcomes; however, due to differences in exclusion criteria and types of units, further study is needed to draw a direct relationship between the electronic surveillance system and outcomes.
How Culture Can Guide Evolution: An Inquiry into Gene/Meme Enhancement and Opposition

We study the relationship between genetic evolution, learning, and culture. We start with the sim ulation environment of Hinton and Nowlan in which individual learning was shown to guide genetic evolution towards a difficult adaptive goal. We then consider, in lieu of individual learn ing, culture in the form of social learning by imitation. Our results demonstrate that when genes and culture cooperate, or enhance one another, culture too is able to guide genetic evolution towards an adaptive goal. Further, we show that social learning is superior to individual learning insofar as it with genetic evolution converges more quickly to the goal. However, the social learn ing algorithm results in slower genetic assimilation of adaptive alleles than with individual learn ing. It is as if, we argue, the adaptive values are stored in the culture rather than in the genes. Finally, we consider what happens when culture and genes pursue diametrically opposed goals. Here we show that culture, in the form of social learning, is no real match when opposed to genet ic evolution with individual learning. In fact, only the most herculean of social learning algorithms is able to keep a neutralizing toe-hold against the slow plodding force of genetic evolution. Finally, our results suggest that in both cases, opposition and enhancement, transmission forces such as the ratio of teacher to learner are central to the success of social learning.
Medication dispensing as an opportunity for patient counseling and approach to drug-related problems

The objective was to describe and evaluate a model of drug dispensing developed and implemented in a community pharmacy in Brazil. This was a descriptive, observational, quasi-experimental study performed in the period between 21 January 2013 and 20 April 2013. The model was evaluated and described in terms of three parameters: structure, process and outcome. The description and assessment of each parameter was performed as follows: (I) Structure: profile of patients, pharmacist's professional profile, physical facility, informational material; (II) Process: drug-related problems, pharmaceutical interventions performed, results of pharmaceutical interventions; (III) Outcome: patient knowledge of medications. Dispensing service improved patient knowledge of medications (p < 0.05), which was associated with pharmacotherapy complexity (p < 0.05). The main problems identified were related to lack of patient knowledge regarding their medication (52.9%). Pharmaceutical interventions were mostly performed directly to the patients (86.3%) by verbal (95.4%) and written (68.2%) information, and most of the problems were completely solved (62.7%). The medicine dispensing model was able to identify and solve drug-related problems and promote an improvement in patient knowledge about medication.
Anti‐senescence effects of DNA methyltransferase inhibitor RG108 in human bone marrow mesenchymal stromal cells

Alteration of DNA methylation is highly associated with ageing and ageing‐related diseases. Remedy of the altered methylation pattern may provide beneficial efficacy in these diseases. In this study, we used a DNA methyltransferase inhibitor, RG108, to investigate the senescence effects in human bone marrow mesenchymal stromal cells (hBM‐MSCs). First, we determined the optimized dose and time of RG108 treatment in hBM‐MSCs to be 5 µM for 48 H, respectively. Under these conditions, the anti‐senescence genes TERT, bFGF, VEGF, and ANG were increased, whereas the senescence‐related genes ATM, p21, and p53 were decreased. The number of β‐galactosidase‐positive cells was significantly decreased in RG108‐treated MSCs, whereas the rates of MSC migration and cellular protection were increased. We have shown that RG108 significantly induces the expression of TERT by blocking methylation at the TERT promoter region. Thus, these data indicate that an optimized dose of RG108 may improve the cell migration, protection, cellular senescence, which may provide a better efficacy of these cells in stem cell therapy.
Developing the Standardized Wound Care Documentation Model: A Delphi Study to Improve the Quality of Patient Care Documentation

OBJECTIVE: The aim of this study was to validate a set of previously developed criteria for wound care documentation and to use the validated criteria as a framework for developing a wound care documentation model. The Skin Integrity component of the Finnish Care Classification, the Finnish Classification of Nursing Diagnosis, and the Finnish Classification of Nursing Interventions serve as the basis for the wound care documentation model. SUBJECTS AND SETTING: Finnish wound care specialists, mainly nurses, from different Finnish hospitals, and from the Finnish Wound Care Society having on average 18 years of experience in wound management. Data were collected using electronic survey technology. METHODS: A Delphi technique was used to develop and validate the documentation system. RESULTS: The final model consists of 7 main categories and 25 subcategories of the Skin Integrity component of the Finnish Classification of Nursing Diagnosis and 5 main categories and 25 subcategories of the Skin Integrity component of the Finnish Classification of Nursing Intervention. Based on the results of the Delphi survey, consensus was reached on all elements of the wound care documentation model. CONCLUSION: The Delphi process was used to develop a wound care documentation model for use in an electronic record to promote systematic documentation of both wound assessment and wound care. Future research should address the utility of this documentation model for nurses with expertise in wound care and generalist nurses.
Pulse-mode macromodular systems

Pulse-mode handshaking is a form of 2-phase handshaking that uses pulses, instead of transitions, to represent events. It combines the conceptual simplicity of the 2-phase protocol (only two events per handshake) with the level based approach of 4-phase handshaking. Pulse-mode macromodules use a new, more concurrent form of operation than that of traditional pulse-mode systems, called Pulse burst operation (PBO). Pulse-mode handshaking is used in the design of a large set of macromodules that can be used to build cost-effective asynchronous systems. The set includes modules that efficiently implement control operations such as sequencing, selection, iteration, concurrency control and resource sharing. An arbiter and converter modules to interface pulse-mode to traditional 2-phase and 4-phase circuits are also included. A packet switch is designed to demonstrate the viability of pulse-mode macromodules to implement complex, high performance systems.
Deciding between Accounts of the Selection Task: A Reply to Oaksford (2002)

Abstract In this paper we report on our attempts to fit the optimal data selection (ODS) model (Oaksford & Chater, 1994; Oaksford, Chater, & Larkin, 2000) to the selection task data reported in Feeney and Handley (2000) and Handley, Feeney, and Harper (2002). Although Oaksford (2002b) reports good fits to the data described in Feeney and Handley (2000), the model does not adequately capture the data described in Handley et al. (2002). Furthermore, across all six of the experiments modelled here, the ODS model does not predict participants’ behaviour at the level of selection rates for individual cards. Finally, when people's probability estimates are used in the modelling exercise, the model adequately captures only 1 out of 18 conditions described in Handley et al. We discuss the implications of these results for models of the selection task and claim that they support deductive, rather than probabilistic, accounts of the task.
Localized Wounding by Heat Initiates the Accumulation of Proteinase Inhibitor II in Abscisic Acid-Deficient Plants by Triggering Jasmonic Acid Biosynthesis

To test whether the response to electrical current and heat treatment is due to the same signaling pathway that mediates mechanical wounding, we analyzed the effect of electric-current application and localized burning on proteinase inhibitor II (Pin2) gene expression in both wild-type and abscisic acid (ABA)-deficient tomato (Lycopersicon esculentum Mill.) and potato (Solanum phureja) plants. Electric-current application and localized burning led to the accumulation of Pin2 mRNA in potato and tomato wild-type plants. Among the treatments tested, only localized burning of the leaves led to an accumulation of Pin2 mRNA in the ABA-deficient plants. Electric-current application, like mechanical injury, was able to initiate ABA and jasmonic acid (JA) accumulation in wild-type but not in ABA-deficient plants. In contrast, heat treatment led to an accumulation of JA in both wild-type and ABA-deficient plants. Inhibition of JA biosynthesis by aspirin blocked the heat-induced Pin2 gene expression in tomato wild-type leaves. These results suggest that electric current, similar to mechanical wounding, requires the presence of ABA to induce Pin2 gene expression. Conversely, burning of the leaves activates Pin2 gene expression by directly triggering the biosynthesis of JA by an alternative pathway that is independent of endogenous ABA levels.
Mice Lacking Monocyte Chemoattractant Protein 1 Have Enhanced Susceptibility to an Interstitial Polymicrobial Infection Due to Impaired Monocyte Recruitment

ABSTRACT Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces monocyte recruitment in a number of different pathologies, including infection. To investigate the role of MCP-1 in protecting a host from a chronic interstitial polymicrobial infection, dental pulps of MCP-1−/− mice and controls were inoculated with six different oral pathogens. In this model the recruitment of leukocytes and the impact of a genetic deletion on the susceptibility to infection can be accurately assessed by measuring the progression of soft tissue necrosis and osteolytic lesion formation. The absence of MCP-1 significantly impaired the recruitment of monocytes, which at later time points was threefold higher in the wild-type mice than in MCP-1−/− mice (P < 0.05). The consequence was significantly enhanced rates of soft tissue necrosis and bone resorption (P < 0.05). We also determined that the MCP-1−/− mice were able to recruit polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls and to produce equivalent levels of Porphyromonas gingivalis-specific total immunoglobulin G (IgG) and IgG1. These results point to the importance of MCP-1 expression and monocyte recruitment in antibacterial defense and demonstrate that antibacterial defense is not due to an indirect effect on PMN recruitment or modulation of the adaptive immune response.
Influence of supervised and nonsupervised training on postural control after an acute anterior cruciate ligament rupture: a three-year longitudinal prospective study.

STUDY DESIGN Prospective randomized longitudinal clinical trial with matched controls. OBJECTIVES To investigate the long-term effect of training on postural control and extremity function after an acute anterior cruciate ligament (ACL) injury. BACKGROUND ACL injuries may cause severe problems with recurrent giving way of the knee and reduced functional capacity. The effect of an acute ACL injury and the effect of various training programs on postural control, as well as the relation between postural control and extremity function after such an injury, have not been studied longitudinally. METHODS Sixty-three consecutive patients, 35 men and 28 women (median age 24 years, quartiles 19-33 years), with an acute nonoperated ACL injury, randomized to neuromuscular supervised or self-monitored training, were examined with stabilometry (amplitude and average speed of center of pressure movements) and a one-leg hop test for distance after 6 weeks (stabilometry only), and after 3, 12, and 36 months, and were compared to a control group. RESULTS Regardless of treatment, center of pressure amplitude was persistently higher in both the injured and uninjured legs during the 3-year follow-up, but average speed was less affected or unaffected compared to the control group. The one-leg hop had normalized in the neuromuscular group at the 12-month follow-up, but was shorter in both legs throughout the 3-year period in the self-monitored group. The median value (quartiles) for injured/uninjured legs at 3 months was 150 cm (120-174 cm)/177 cm (140-199 cm), at 12 months was 174 cm (140-200 cm)/180 cm (150-202 cm), and at 36 months was 172 cm (146-200 cm)/178 cm (150-200 cm) in the self-monitored group, compared to the control group (median 186 cm, quartiles 177-216 cm). CONCLUSIONS The higher center of pressure amplitude in both legs over the 3-year period indicate persistently impaired postural control in single-limb stance. However, functional performance, as measured with the one-leg hop test, was restored by neuromuscular training, but not by self-monitored training.
Notas sobre los números del p'úrhépecha

El presente articulo le ofrece un bosquejo de la numeracion cardinal del p'urhepecha (lengua indigena hablada en el occidente de Mexico). Los numeros han sido tipificados en cinco series principales, a partir de de su forma y de su independencia lexica. Se incluyen algunos procesos derivativos a partir de las raices numerales, lo que da cuenta de la complejidad morfologica de esta clase de palabras. La presentacion de estos materiales busca sensibilizar a los responsables de la educacion p'urhepecha para que incluyan en sus programas y libros el amplio mundo de los numeros de esta lengua.
Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature

Immunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. We critically review the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of α‐methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. We also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high‐grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.
1,25‐dihydroxyvitamin D3 and the vitamin D analogue KH1060 induce hyperproliferation in normal mouse epidermis

Abstract 1,25‐dihydroxyvitamin D3 (calcitriol) affects differentiation and proliferation of epidermal keratinocytes in vitro and in vivo. We have studied the topical effects of calcitriol (0.08 2.0 μg/ml) and of a new vitamin D analogue, the epi‐20‐analogue KH1060 (0.4 –2.0 μg/ml) on epidermal proliferation in normal hairless mice. Epidermis was examined at intervals from 4 h to 8 days after a single‐dose application. The mitotic rate was assessed by the stathmokinetic method and hyperplasia was scored in histological sections. Cell cycle parameters were measured by bivariale bromodeoxyuridine (BrdUrd)/DNA flow cytometry on isolated epidermal basal cells after pulse‐labelling with BrdUrd. Both calcitriol and KM 1060 induced a dose‐ and time‐dependent increase in the mitotic rate and in hyperplasia, the latter drug being the most effective. Calcitriol and KH1060 induced changes in the cell cycle traverse compatible with the regenerative reaction seen after other hyperplasiogens, but with an additionally increased accumulation of cells in the G2 phase. This is similar to that seen after topical application of retinoic acid to mouse skin. Our results are thus in contrast to the anti‐proliferative effects of calcitriol observed in vitro and following treatment of the hyperproliferative disease psoriasis with calcitriol as well as other vitamin D analogues.
Characterization of prototype and clinically defined strains of Streptococcus suis by genomic fingerprinting

A collection of Streptococcus suis strains from animal and human infections was examined for DNA-banding patterns after restriction endonuclease digestion and agarose gel electrophoresis. The endonuclease HaeIII produced the most discriminating restriction profiles among 23 serotypes studied. DNA from serotypes 9, 11, 12, and 16 was resistant to HaeIII cleavage. DNA from serotypes 9 through 16 was cleaved with HindIII and showed substantial genomic differences. We also examined 106 epidemiologically unrelated strains isolated from cases of pig meningitis or pneumonia and 5 strains isolated from cases of human meningitis in order to compare genomic fingerprinting and serotyping as epidemiological tools. Heterogeneity was found among fingerprints of serologically identical isolates, indicating genetic diversity within some serotypes. DNA fingerprints of some serotype 2 strains from different sources appeared identical, suggesting a clonal relationship among strains of this serotype. The data suggest that this technique represents an important tool for examining the natural history of disease caused by S. suis.
Global Mammal Conservation: What Must We Manage?

We present a global conservation analysis for an entire “flagship” taxon, land mammals. A combination of rarity, anthropogenic impacts, and political endemism has put about a quarter of terrestrial mammal species, and a larger fraction of their populations, at risk of extinction. A new global database and complementarity analysis for selecting priority areas for conservation shows that ∼11% of Earth's land surface should be managed for conservation to preserve at least 10% of terrestrial mammal geographic ranges. Different approaches, from protection (or establishment) of reserves to countryside biogeographic enhancement of human-dominated landscapes, will be required to approach this minimal goal.
The Perceptual-Mnemonic/Feature Conjunction Model of Perirhinal Cortex Function

The perirhinal cortex was once thought to be “silent cortex”, virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a “medial temporal lobe (MTL) memory system”. This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of “feature ambiguity”. These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum.
Restricted fetal growth in sudden intrauterine unexplained death

Background. Unexplained antepartum stillbirth is a common cause of perinatal death, and identifying the fetus at risk is a challenge for obstetric practice. Intrauterine growth restriction (IUGR) is associated with a variety of adverse perinatal outcomes, but reports on its impact on unexplained stillbirths by population‐based birthweight standards have been varying, including both unexplained and unexplored stillbirths.