Miracle-dz/UniFAR-FTUs huggingface dataset:
Different CaV1.3 Channel Isoforms Control Distinct Components of the Synaptic Vesicle Cycle in Auditory Inner Hair Cells

The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Cav1.3 channels and require otoferlin as Ca2+ sensor, but whether they use the same Cav1.3 isoforms is still unknown. Using whole-cell patch-clamp recordings in posthearing mice, we show that only a proportion (∼25%) of the total Ca2+ current in IHCs displaying fast inactivation and resistance to 20 μm nifedipine, a l-type Ca2+ channel blocker, is sufficient to trigger RRP but not SRP exocytosis. This Ca2+ current is likely conducted by short C-terminal isoforms of Cav1.3 channels, notably Cav1.342A and Cav1.343S, because their mRNA is highly expressed in wild-type IHCs but poorly expressed in Otof−/− IHCs, the latter having Ca2+ currents with considerably reduced inactivation. Nifedipine-resistant RRP exocytosis was poorly affected by 5 mm intracellular EGTA, suggesting that the Cav1.3 short isoforms are closely associated with the release site at the synaptic ribbons. Conversely, our results suggest that Cav1.3 long isoforms, which carry ∼75% of the total IHC Ca2+ current with slow inactivation and confer high sensitivity to nifedipine and to internal EGTA, are essentially involved in recruiting SRP vesicles. Intracellular Ca2+ imaging showed that Cav1.3 long isoforms support a deep intracellular diffusion of Ca2+. SIGNIFICANCE STATEMENT Auditory inner hair cells (IHCs) encode sounds into nerve impulses through fast and indefatigable Ca2+-dependent exocytosis at their ribbon synapses. We show that this synaptic process involves long and short C-terminal isoforms of the Cav1.3 Ca2+ channel that differ in the kinetics of their Ca2+-dependent inactivation and their relative sensitivity to the l-type Ca2+ channel blocker nifedipine. The short C-terminal isoforms, having fast inactivation and low sensitivity to nifedipine, mainly control the fast fusion of the readily releasable pool (RRP); that is, they encode the phasic exocytotic component. The long isoforms, with slow inactivation and great sensitivity to nifedipine, mainly regulate the vesicular replenishment of the RRP; that is, the sustained or tonic exocytosis.
Study of male–mediated gene flow across a hybrid zone in the common shrew (Sorex araneus) using Y chromosome

Abstract Despite many studies, the impact of chromosome rearrangements on gene flow between chromosome races of the common shrew (Sorex araneus Linnaeus, 1758) remains unclear. Interracial hybrids form meiotic chromosome complexes that are associated with reduced fertility. Nevertheless comprehensive investigations of autosomal and mitochondrial markers revealed weak or no barrier to gene flow between chromosomally divergent populations. In a narrow zone of contact between the Novosibirsk and Tomsk races hybrids are produced with extraordinarily complex configurations at meiosis I. Microsatellite markers have not revealed any barrier to gene flow, but the phenotypic differentiation between races is greater than may be expected if gene flow was unrestricted. To explore this contradiction we analyzed the distribution of the Y chromosome SNP markers within this hybrid zone. The Y chromosome variants in combination with race specific autosome complements allow backcrosses to be distinguished and their proportion among individuals within the hybrid zone to be evaluated. The balanced ratio of the Y variants observed among the pure race individuals as well as backcrosses reveals no male mediated barrier to gene flow. The impact of reproductive unfitness of backcrosses on gene flow is discussed as a possible mechanism of the preservation of race-specific morphology within the hybrid zone.
Regional variation in the surface morphology of the epithelium of the rat ductuli efferentes, ductus epididymidis and vas deferens

The luminal surface ofepithelial cells lining the ductuli efferentes, ductus epididymidis and first portion of the vas deferens were studied with the scanning electron microscope. In ductuli efferentes obvious ciliated cells are identified and it is shown that on non‐ciliated cells the short microvilli adhere to one another to form clumps of microvilli. In the epididymis two cell types are described and can be identified as principal cells and clear cells based on the presence or absence of microvilli. Clear cells vary in number along the duct, being most numerous distally. Their surface morphology is also most variable distally. In the vas deferens, principal cells with surface microvilli are easily identified; but in addition, a second cell type is seen, the identity of which is not known.
Validation of cardiovascular diagnoses in the Greenlandic Hospital Discharge Register for epidemiological use

ABSTRACT Cardiovascular disease (CVD) is one of the leading causes of death worldwide. In Greenland, valid estimates of prevalence and incidence of CVD do not exist and can only be calculated if diagnoses of CVD in the Greenlandic Hospital Discharge Register (GHDR) are correct. Diagnoses of CVD in GHDR have not previously been validated specifically. The objective of the study was to validate diagnoses of CVD in GHDR. The study was conducted as a validation study with primary investigator comparing information in GHDR with information in medical records. Diagnoses in GHDR were considered correct and thus valid if they matched the diagnoses or the medical information in the medical records. A total of 432 online accessible medical records with a cardiovascular diagnosis according to GHDR from Queen Ingrid’s Hospital from 2001 to 2013 (n=291) and from local health care centres from 2007 to 2013 (n=141) were reviewed. Ninety-nine and ninety-two percent of discharge diagnosis in GHDR from Queen Ingrid’s Hospital and local health care centres were correct in comparison with diagnoses in the medical record indicating valid registration practice. The correctness of cardiovascular diagnoses in GHDR was considered high in terms of acceptable agreement between medical records and diagnoses in GHDR. Cardiovascular diagnoses are valid for epidemiological use.
Burkholderia puraquae sp. nov., a novel species of the Burkholderia cepacia complex isolated from hospital settings and agricultural soils.

Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). These opportunistic pathogens are also widely distributed in natural and man-made environments. After a 12-year epidemiological surveillance involving Bcc bacteria from respiratory secretions of Argentinean patients with CF and from hospital settings, we found six isolates of the Bcc with a concatenated species-specific allele sequence that differed by more than 3 % from those of the Bcc with validly published names. According to the multilocus sequence analysis (MLSA), these isolates clustered with the agricultural soil strain, Burkholderia sp. PBP 78, which was already deposited in the PubMLST database. The isolates were examined using a polyphasic approach, which included 16S rRNA, recA, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), DNA base composition, average nucleotide identities (ANIs), fatty acid profiles, and biochemical characterizations. The results of the present study demonstrate that the seven isolates represent a single novel species within the Bcc, for which the name Burkholderia puraquae sp. nov. is proposed. Burkholderia puraquae sp. nov. CAMPA 1040T (=LMG 29660T=DSM 103137T) was designated the type strain of the novel species, which can be differentiated from other species of the Bcc mainly from recA gene sequence analysis, MLSA, ANIb, MALDI-TOF MS analysis, and some biochemical tests, including the ability to grow at 42 °C, aesculin hydrolysis, and lysine decarboxylase and β-galactosidase activities.
Insulin‐like growth factor‐1 prevents age‐related decrease in specific force and intracellular Ca2+ in single intact muscle fibres from transgenic mice

In the present work we test the hypothesis that sustained transgenic overexpression of insulin‐like growth factor‐1 (IGF‐1) in skeletal muscle prevents age‐related decreases in myoplasmic Ca2+ concentration and consequently in specific force in single intact fibres from the flexor digitorum brevis (FDB) muscle from the mouse. Measurements of IGF‐1 concentration in FDB muscle showed higher levels in transgenic than in wild‐type mice at all ages. The specific tetanic force decreased significantly in single muscle fibres from old (286 ± 22 kPa) compared to young wild‐type (455 ± 28 kPa), young transgenic (423 ± 43 kPa), and old transgenic mice (386 ± 15 kPa) (P < 0.05). These results are consistent with measurements in whole FDB muscles. The peak Ca2+ concentration values in response to prolonged stimulation were: 1.47 ± 0.15, 1.70 ± 0.29, 0.97 ± 0.13 and 1.7 ± 0.22 μm, in fibres from young wild‐type, young transgenic, old wild‐type and old transgenic mice, respectively. The effects of caffeine on FDB fibres support the conclusion that the age‐related decline in peak myoplasmic Ca2+ and specific force is not explained by sarcoplasmic reticulum Ca2+ depletion. Immunohistochemistry in muscle cross‐sections was performed to determine whether age and/or IGF‐1 overexpression induce changes in fibre type composition. The relative percentages of type IIa, IIx and I myosin heavy chain (MHC) isoforms did not change significantly with age or genotype. Therefore, IGF‐1 prevents age‐related decline in peak intracellular Ca2+ and specific force in a muscle that does not exhibit changes in fibre type composition with senescence.
Developing a Taxonomy and an Ontology of Nurses' Patient Clinical Summaries

Nurses prepare a summary of patient information that they consult and update throughout the shift. This document is believed to be integral to cognition, working memory, and decision-making. While serving as a key support to nursing practice, this summary also represents risks to patient safety. Characterized as a PCCAT, or Personally Created Cognitive Artifact, studies of this document in the context of nursing practice have not been reported. The absence of reported research, the importance of the document to nurse cognition and practice, and related safety risks prompted the research that this paper discusses. A taxonomy was developed through the analysis and coding of 151 PCCATs. Further analysis and mapping provided an ontology of the PCCAT. Content differences were noted between nursing units and among nurses. This may reflect differences in unit-based culture and/or differences in the patient complexity. The interaction between culture and perceived complexity of practice is one of the great difficulties in generating automated information systems for clinical practice settings. This paper is part of a larger research protocol that explores meta-level knowledge structures and revision to the understanding of the granularity of nursing knowledge. Development of a taxonomy and ontology of the nurse PCCAT, an important component of the larger research protocol, is described in this paper.
Flibanserin for the treatment of hypoactive sexual desire disorder in premenopausal women

Introduction: Hypoactive sexual desire disorder (HSDD) is the most common form of female sexual dysfunction (FSD). Some theories suggest that HSDD has a neurobiological component linked to neurotransmitter imbalances. Flibanserin is the only FDA-approved treatment of HSDD; before its approval, the disorder was often left untreated or interventions were made using evidence-based psychological methods or ‘off-label’ use of bupropion, testosterone and other dopaminergic agents. Areas covered: Flibanserin, a multifunctional serotonin agonist/antagonist, is approved as a nonhormonal option designed specifically for the treatment of HSDD. Flibanserin has been shown to cause statistically significant increases in the number of satisfying sexual events and in sexual desire scores on standardized/validated measures while reducing FSD-related distress of premenopausal women diagnosed with HSDD. Similar efficacy has been demonstrated in a smaller group of postmenopausal women also affected by HSDD. The side effects of flibanserin include dizziness, somnolence, nausea and (rarely) syncope, and are comparable to other CNS drugs. Expert opinion: While there has been debate over the approval of flibanserin for treatment of HSDD, it is evident that flibanserin provides meaningful relief to women suffering from a common sexual dysfunction and is an important addition to the field of women’s health.
Slow- and tight-binding inhibitors of the 85-kDa human phospholipase A2.

A trifluoromethyl ketone analogue of arachidonic acid in which the COOH group is replaced with COCF3 (AACOCF3) was prepared and found to be a tight- and slow-binding inhibitor of the 85-kDa cytosolic human phospholipase A2 (cPLA2). Enzyme inhibition was observed when AACOCF3 was tested in assays using either phospholipid vesicles or phospholipid/Triton X-100 mixed micelles. The fact that the inhibition developed over several minutes in both assays establishes that AACOCF3 inhibits by direct binding to the enzyme rather than by decreasing the fraction of enzyme bound to the substrate interface. From the measured values of the inhibitor association and dissociation rate constants, an upper limit of the equilibrium dissociation constant for the Ca(2+). AACOCF3.PLA2 complex of 5 x 10(-5) mole fraction was obtained. Thus, detectable inhibition of cPLA2 by AACOCF3 occurs when this compound is present in the assay at a level of one inhibitor per several thousand substrates. Arachidonic acid analogues in which the COOH group is replaced by COCH3, CH(OH)CF3, CHO, or CONH2 did not detectably inhibit the cPLA2. The arachidonyl ketones AACOCF2CF3 and AACOCF2Cl were found by 19F NMR to be less hydrated than AACOCF3 in phospholipid/Triton X-100 mixed micelles, and compared to AACOCF3 these compounds are also weaker inhibitors of cPLA2. In keeping with the fact that cPLA2 displays substrate specificity for arachidonyl-containing phospholipids, the arachidic acid analogue C19H39COCF3 is a considerably less potent inhibitor compared to AACOCF3. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of an Essential Oil Mouthrinse, with and without Fluoride, on Plaque Metabolic Acid Production and pH after a Sucrose Challenge

This clinical study evaluated the effect of rinsing with an essential oil-containing antiseptic mouthrinse, with or without 100 mg/kg fluoride ion, on the plaque metabolic acid production and plaque pH response after a sucrose challenge. This observer-blind, randomized study used a three-way crossover design. Twenty-four subjects rinsed with 20 ml of one of the following rinses: (1) essential oil (EO) mouthrinse, (2) essential oil mouthrinse plus 100 mg/kg fluoride, or (3) negative control, for 30 s, twice daily for 16 days. On day 17, 1 h after the last mouthrinse, subjects rinsed with 20 ml of mass fraction 10% sucrose solution for 1 min. Seven minutes after the sucrose challenge, supragingival plaque was collected from molar and premolar teeth. Plaque pH and metabolic acid ions were analyzed using a micro pH electrode and capillary electrophoresis, respectively. The results showed that after EO mouthrinse dental plaque produced 36% less lactate, 36% less acetate and 44% less propionate than after the negative control rinse. The dental plaque also exhibited a pH 0.42 unit higher after EO rinse than after the negative control rinse. These results were not affected by the addition of 100 mg/kg fluoride to the EO mouthrinse. From these results we concluded that this EO antiseptic mouthrinse, with or without fluoride ion, is effective in reduction of plaque acidogenicity after a sucrose challenge.
Predictive value of intraoperative neurophysiological monitoring during cervical spine surgery: a prospective analysis of 1055 consecutive patients.

OBJECT Despite the growing use of multimodal intraoperative monitoring (IOM) in cervical spinal surgery, limited data exist regarding the sensitivity, specificity, and predictive values of such a technique in detecting new neurological deficits in this setting. The authors sought to define the incidence of significant intraoperative electrophysiological changes and new postoperative neurological deficits in a cohort of patients undergoing cervical surgery. METHODS The authors conducted a prospective analysis of a consecutive series of patients who had undergone cervical surgery during a 5-year period at a university-based neurosurgical unit, in which multimodal IOM was recorded. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were determined using standard Bayesian techniques. The study population included 1055 patients (614 male and 441 female) with a mean age of 55 years. RESULTS The IOM modalities performed included somatosensory evoked potential (SSEP) recording in 1055 patients, motor evoked potential (MEP) recording in 26, and electromyography (EMG) in 427. Twenty-six patients (2.5%) had significant SSEP changes. Electromyographic activity was transient in 212 patients (49.6%), and 115 patients (26.9%) had sustained burst or train activity. New postoperative neurological deficits occurred in 34 patients (3.2%): 6 had combined sensory and motor deficits, 7 had new sensory deficits, 9 had increased motor weakness, and 12 had new root deficits. Of these 34 patients, 12 had spinal tumors, of which 7 were intramedullary. Overall, of the 34 new postoperative deficits, 21 completely resolved, 9 partially resolved, and 4 had no improvement. The deficits that completely resolved did so on average 3.3 months after surgery. Patients with deficits that did not fully resolve (partial or no improvement) were followed up for an average of 1.8 years after surgery. Somatosensory evoked potentials had a sensitivity of 52%, a specificity of 100%, a PPV of 100%, and an NPV of 97%. Motor evoked potential sensitivity was 100%, specificity 96%, PPV 96%, and NPV 100%. Electromyography had a sensitivity of 46%, specificity of 73%, PPV of 3%, and an NPV of 97%. CONCLUSIONS Combined neurophysiological IOM with EMG and SSEP recording and the selective use of MEPs is helpful for predicting and possibly preventing neurological injury during cervical spine surgery.
New paradigms in the management of alloimmune refractoriness to platelet transfusions

Purpose of reviewFollowing transfusion or pregnancy, a significant number of patients develop antibodies to class I human leukocyte antigen. Some will exhibit platelet transfusion refractoriness, defined as inappropriately low platelet count increments after two or more consecutive transfusions. Unfortunately, failure of at least two products is required before an immunologic work-up is undertaken. Among those diagnosed with immune refractoriness, there is no standard method for identifying platelet products likely to be effective. Recent findingsRecent advances in detection and identification of human leukocyte antigen antibody may permit pretransfusion screening of selected patients and provide guidance in choosing the optimal product. An approach more like that for red cell alloimmunized patients, in which one provides products guided solely by the antibody profile, is preferable to selection based on educated guesswork when human leukocyte antigen identical units are unavailable, and offers some advantages over platelet crossmatching. SummaryThis review presents a literature-based algorithm with which to approach the management of platelet refractory individuals, focusing on newer technology to maximize the post-transfusion yield of matched units. Strategies are presented that allow selection of more effective products for difficult, broadly alloimmunized individuals, including patients who have developed antibodies to human platelet antigens.
Phosphate decreases osteoclastogenesis in coculture of osteoblast and bone marrow.

Alkaline phosphatase (ALP) activity increases dramatically during osteoblast maturation, a phenomenon that is related to calcification of teeth and bone. Although the relation between ALP and calcification is widely known, there is a paucity of date relating ALP and osteoclast formation. Very recently, we showed that osteoblast maturation suppresses osteoclast formation. However, the relation between osteoblast maturation and osteoclastogenesis remains unclear. In the present study, we examined the effect of extracellular phosphate on osteoclastogenesis. As osteoblasts matured, osteoclast formation decreased, and ALP activity and inorganic phosphate in extracellular matrix increased. Inorganic phosphate in extracellular matrix and extracellular phosphate was suppressed osteoclast formation. These results suggest that phosphate released by ALP may be related not only to calcification but also to suppression of osteoclastogenesis.
Low cost point of care estimation of Hemoglobin levels

Anemia is a public health problem that affects populations in low-income and middle-income countries. World Health Organization defines anemia status by hemoglobin (Hb) concentrations. Our aim is to develop a method to estimate Hb levels in low resource settings. It is proposed to take an image of a drop of blood on a filter strip under controlled conditions and then estimate the Hb level of the blood using an image processing algorithm. In the first part of the paper we discuss the protocol used to simulate the controlled conditions needed to capture the image of the blood drop. In the second part of the paper, blood drop of 33 individuals were collected with the prototype. A classification tree and correlation based approach to feature selection was used to classify 4 levels of Hb (Class I - Hb above 12 g/dl, Class II - Hb between 10 and 12, Class III - Hb between 8 and 10, Class IV - Hb below 8) in the data. The features selected (`Y' from XYZ color space, `a' from Lab color space and `S' from HSI color space) from classification tree were used to train an artificial neural network. The data was partitioned into 17 training samples and 16 testing samples. The confusion matrix obtained on the testing set is desirable, with overall accuracy of 82%, sensitivity of 83% and specificity of 82%. This result on a small dataset is encouraging and shows that color image analysis of blood can be used to estimate Hb with the image being captured is under standard conditions.
Do I Know What I’m Doing? Cognitive Dissonance and Action Identification Theory

Abstract Our main purpose was to explore hypotheses derived from the Identification of Action Theory in a particular situation that is, a dissonant situation. Thus, we varied the identification (low versus high-level) of a problematic behavior (to stop speaking for 24 hours) in the forced compliance paradigm. Two modes of dissonance reduction were presented: cognitive rationalization (classical attitude-change) and behavioral rationalization (target behavior: to stop speaking for 48 hours). As predicted, the results showed that high-level identity of action leads to cognitive rationalization whereas low-level identity leads to behavioural rationalization. Thus, participants identifying the problematic behavior at a low-level were more inclined to accept the target behavior, compared with participants identifying their problematic behavior at a higher-level. These results are of particular interest for understanding the extent to which the understanding of the discrepant act interferes with the cognitive processes of dissonance reduction.