Miracle-dz/UniFAR-FTUs huggingface dataset:
JUMPING: POWER OR IMPULSE?

I write in response to the manuscript by Canavan and Vescovi (2) that revisited attempts to predict power output on the basis of height achieved during vertical jumping. Adamson and Whitney (1) and Smith (4) indicated that such approaches are misguided. Moreover, the misapplication of mechanical constructs in the context of exercise was highlighted in this journal by Knuttgen (3). The warnings have gone largely unheeded, and the infatuation with power as a mechanical construct, supposedly to indicate maximal intensity exercise performance, persists. The ability to jump either horizontally or vertically is dependent principally on the velocity at takeoff. From Newton’s second law of motion, this velocity is attributable to the preceding impulse and is enshrined in the impulse– momentum relationship. It is muscle’s capability to develop impulse not its ability to generate power that is the point at issue. The force–time history can be explored by considering characteristics of the profile or area under the force–time curve. It is the interaction of force development and its manipulation over time that explains rather than simply describes performance. Integration of the force–time history can be used to provide a velocity–time profile of the body’s center of mass and so provide a basis for calculations of the products of force and velocity. Ostensibly, these provide instantaneous values of power output that are seductive. The failings of this approach were demonstrated by Adamson and Whitney (1) and Smith (4). Attempts to justify the use of “power” to explore jumping are often based on the strong relationship between this supposed measure and height jumped. Indeed, this is the approach taken by Canavan and Vescovi (2), who use jump height and body mass as predictors for an R of 0.92; they compound matters by claiming that there is no probability that their result could have occurred by chance. Such a relationship might well be simply fortuitous; the relationship between impulse and jump height is perfect; that is, 1. Efforts to explain jumping in the context of power are at best misguided and a distraction and at worst a misrepresentation of the mechanical constructs involved. Such approaches probably reveal more about investigators’ understanding of underlying mechanics than they do about explanations rather than simple descriptions of performance.
Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in vivo

Abstract Loss of function mutations in progranulin (GRN) cause frontotemporal dementia, but how GRN haploinsufficiency causes neuronal dysfunction remains unclear. We previously showed that GRN is neurotrophic in vitro. Here, we used an in vivo axonal outgrowth system and observed a delayed recovery in GRN−/− mice after facial nerve injury. This deficit was rescued by reintroduction of human GRN and relied on its C-terminus and on neuronal GRN production. Transcriptome analysis of the facial motor nucleus post injury identified cathepsin D (CTSD) as the most upregulated gene. In aged GRN−/− cortices, CTSD was also upregulated, but the relative CTSD activity was reduced and improved upon exogenous GRN addition. Moreover, GRN and its C-terminal granulin domain granulinE (GrnE) both stimulated the proteolytic activity of CTSD in vitro. Pull-down experiments confirmed a direct interaction between GRN and CTSD. This interaction was also observed with GrnE and stabilized the CTSD enzyme at different temperatures. Investigating the importance of this interaction for axonal regeneration in vivo we found that, although individually tolerated, a combined reduction of GRN and CTSD synergistically reduced axonal outgrowth. Our data links the neurotrophic effect of GRN and GrnE with a lysosomal chaperone function on CTSD to maintain its proteolytic capacity.
Modulation in the mirror neuron system when action prediction is not satisfied

The ability to understand competitive games is closely connected to the mirror neuron system (MNS). This network is activated not only when an action is performed, but also when it is observed. Apart from allowing the understanding of actions performed by others, the MNS has been implicated in predicting subsequent actions. However, the results concerning the modulation of this network by the final outcome of these predictions are contradictory. These contradictions may be related to the use of complex experimental conditions. The aim of this research is to identify changes in the activity of the MNS when the predictions are or are not satisfied in a simple intransitive action‐based game. An event‐related functional magnetic resonance imaging study was conducted. It consisted of the observation of videos with two actors playing the well‐known rock–paper–scissors game. The participants were asked to predict the response of the second actor when the first actor performed one of the three possible actions. In some videos (congruents) the prediction was satisfied, but in the rest of the videos (incongruents) the prediction was not satisfied. When the result was shown, higher activity in the MNS was observed in the congruent videos than in the incongruent ones. Therefore, the observation of a simple manual game leads to a significant activation of the MNS, and this activity seems to be modulated by the final outcome of a prediction, and when predictions are satisfied the activity is higher.
HEMODYNAMIC CHANGES AFTER UNCLAMPING OF THE INFERIOR VENA CAVA DURING ORTHOTOPIC LIVER TRANSPLANTATION

Orthotopic liver transplantation (OLT), first performed in 1963, has become a successful therapy for many patients with end-stage liver disease (1) and the clinical use of venovenous bypass, thrombelastography, and the rapid infusion system has streamlined intraoperative care (2-4). Nevertheless, sudden physiologic changes seen on reperfusion of the grafted liver (postreperfusion syndrome, PRS) remain a challenge to anesthesiologists. These changes include acute deterioration of cardiovascular performance, hypothermia, imbalances in electrolyte levels and acid-base state, coagulopathy, and hyperglycemia (5-9). The most dramatic and clinically significant changes are seen in the cardiovascular system. I. Hemodynamic changes during OLT Discussion of hemodynamic hanges that occur during OLT is imperative to understand the postreperfusion syndrome. OLT has three distinctive stages. The preanhepatic stage extends from skin incision to the skeletonization of the hepatic vasculature. During this period, the major hemodynamic changes are associated with decreased preload resulting from
Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro

The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input–output transformation we performed whole‐cell and perforated‐patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short‐term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short‐term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter‐spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low‐frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high‐frequency pallidal output may continuously modulate EP firing.
Psychiatric Crisis Management in the Emergency Care Hospital Network

Since psychiatric crisis treatment is crucial in mental health care, this study aimed to characterize the psychiatric crisis in the hospital emergency services of Natal/RN. Semi-structured interviews were conducted with 33 professionals employed in four local public hospitals. The results revealed the absence of adequate beds for psychiatric conditions, scarcity of psychiatric drugs, lack of clarity regarding diagnostic criteria, treatment based on chemical restraint and inpatient care as a priority strategy. Furthermore, there is fragmentation of the work processes with physician centrality in the management of crisis, disarticulation between hospitals and other services of the psychosocial care network and systematic referrals to psychiatric hospital. We conclude that the configuration of the local hospital network does not present satisfactory responsiveness to psychiatric crisis situations and its clinical and institutional weaknesses reflect the process of psychiatric reform in the region.
Localization and expression of GABA transporters in the suprachiasmatic nucleus

GABA is a principal neurotransmitter in the suprachiasmatic hypothalamic nucleus (SCN), the master circadian clock. Despite the importance of GABA and GABA uptake for functioning of the circadian pacemaker, the localization and expression of GABA transporters (GATs) in the SCN has not been investigated. The present studies used Western blot analysis, immunohistochemistry and electron microscopy to demonstrate the presence of GABA transporter 1 (GAT1) and GAT3 in the SCN. By using light microscopy, GAT1 and GAT3 were co‐localized throughout the SCN, but were not expressed in the perikarya of arginine vasopressin‐ or vasoactive intestinal peptide‐immunoreactive (‐ir) neurons of adult rats, nor in the neuronal processes labelled with the neurofilament heavy chain. Using electron microscopy, GAT1‐ and GAT3‐ir was found in glial processes surrounding unlabelled neuronal perikarya, axons, dendrites, and enveloped symmetric and asymmetric axo‐dendritic synapses. Glial fibrillary acidic protein‐ir astrocytes grown in cell culture were immunopositive for GAT1 and GAT3 and both GATs could be observed in the same glial cell. These data demonstrate that synapses in the SCN function as ‘tripartite’ synapses consisting of presynaptic axon terminals, postsynaptic membranes and astrocytes that contain GABA transporters. This model suggests that astrocytes expressing both GATs may regulate the extracellular GABA, and thereby modulate the activity of neuronal networks in the SCN.
Predictors of dental service utilization among visually impaired people in Chiang Mai, Thailand

The purposes of this cross-sectional study were to examine factors associated with utilization of dental health services among visually impaired people and also identify barriers affecting such utilization. A structured questionnaire and an oral examination were used to collect data in January, 2013. In total, 266 visually impaired people participated in the study. Data were analyzed using chi-square tests and multiple logistic regression. The utilization of dental health services in the past year among visually impaired people was 26.3%. Based on the Chi-square tests, education, occupation, perception of oral status, perception of oral health problems and perceptions of the oral health service system were found to be statistically significant associated with dental service utilization. In logistic regression, significant predictors of dental service utilization among visually impaired people included perception of oral status (adj OR = 4.45, 95% CI = 1.41-14.05), perception of oral health problems (adj OR = 4.66, 95% CI = 1.96-11.07) and perception of the dental service system (adj OR = 2.44, 95% CI = 1.32-4.49). The three most commonly reported barriers to dental visits were “no one takes me to the dentist”, “not enough time” and “waiting until the pain gets worse”. The findings suggested that the significant key factor to increase utilization among visually impaired people is providing an appropriate oral health education to improve the knowledge of oral health care, and finally lead to change the perception of oral problems in these people. Furthermore, special dental service system should be established to minimize barriers to care and serve needs of these people.
Different interaction modes for the default mode network revealed by resting state functional magnetic resonance imaging

The default mode network (DMN), which, in the resting state, is in charge of both the brain's intrinsic mentation and its reflexive responses to external stimuli, is recognized as an essential network in the human brain. These two roles of mentation and reflexive response recruit the DMN nodes and other task networks differently. Existing research has revealed that the interactions inside the DMN (between nodes within the DMN) and outside the DMN (between nodes in the DMN and nodes in task networks) have different modes, in terms of both strength and timing. These findings raise interesting questions. For example, are the internal and external interactions of the DMN equally linear or nonlinear? This study examined these interaction patterns using datasets from the Human Connectome Project. A maximal information‐based nonparametric exploration statistics strategy was utilized to characterize the full correlations, and the Pearson correlation was used to capture the linear component of the full correlations. We then contrasted the level of linearity/nonlinearity with respect to the internal and external interactions of the DMN. After a brain‐wide exploration, we found that the interactions between the DMN and the sensorimotor‐related networks (including the sensorimotor, sensory association, and integration areas) showed more nonlinearity, whereas those between the intra‐DMN nodes were similarly less nonlinear. These findings may provide a clue for understanding the underlying neuronal principles of the internal and external roles of the DMN.
Microtubule cytoskeleton regulates connexin 43 localization and cardiac conduction in cardiomyopathy caused by mutation in A-type lamins gene.

Mutations in the lamin A/C gene (LMNA) cause an autosomal dominant inherited form of dilated cardiomyopathy associated with cardiac conduction disease (hereafter referred to as LMNA cardiomyopathy). Compared with other forms of dilated cardiomyopathy, mutations in LMNA are responsible for a more aggressive clinical course due to a high rate of malignant ventricular arrhythmias. Gap junctions are intercellular channels that allow direct communication between neighboring cells, which are involved in electrical impulse propagation and coordinated contraction of the heart. For gap junctions to properly control electrical synchronization in the heart, connexin-based hemichannels must be correctly targeted to intercalated discs, Cx43 being the major connexin in the working myocytes. We here showed an altered distribution of Cx43 in a mouse model of LMNA cardiomyopathy. However, little is known on the molecular mechanisms of Cx43 remodeling in pathological context. We now show that microtubule cytoskeleton alteration and decreased acetylation of α-tubulin lead to remodeling of Cx43 in LMNA cardiomyopathy, which alters the correct communication between cardiomyocytes, ultimately leading to electrical conduction disturbances. Preventing or reversing this process could offer a strategy to repair damaged heart. Stabilization of microtubule cytoskeleton using Paclitaxel improved intraventricular conduction defects. These results indicate that microtubule cytoskeleton contributes to the pathogenesis of LMNA cardiomyopathy and that drugs stabilizing the microtubule may be beneficial for patients.
The persistent legacy of the 1918 influenza virus.

Descendants of the H1N1 influenza A virus that caused the catastrophic and historic pandemic of 1918–1919 continue to contribute their genes to new viruses, causing new pandemics, epidemics, and epizootics. Drs. David Morens, Jeffery Taubenberger, and Anthony Fauci discuss the influenza A events of the past 91 years.
Discordant Aortic Valve Morphology in Monozygotic Twins: A Clinical Case Series.

Importance Bicuspid aortic valve (BAV) is considered an autosomal dominant condition, which is commonly associated with thoracic aortic aneurysm. Both conditions pose the risk of valvular and aortic complications not only for affected patients but also for genetically related persons as well. The genetic underpinnings of these disease processes, which are in various stages of elucidation, have implications for screening and risk prognostication. Objective To analyze genetic differences between 2 pairs of monozygotic twins that had discordant aortic valve morphology, with 1 twin in each pair having a BAV and the other having a trileaflet aortic valve. Design, Setting, and Participants Two pairs of twins that were objectively determined to be monozygotic were examined at a tertiary care medical center associated with an academic medical center. Aortic valves that were surgically excised for clinical indications were examined for morphology. Whole-exome sequencing was performed for the twin pair that had discordance of aortic valve and aortic aneurysm. In the second pair, targeted gene sequencing of 25 genes known to be associated with BAV and/or thoracic aortic aneurysm was performed. In each pair, the twin with a BAV underwent surgical aortic valve replacement for clinical indications. Main Outcomes and Measures Genetic coding variations between monozygotic twins using whole-exome sequencing and targeted gene sequencing. Results This case series included 2 pairs of male monozygotic twins; one pair was aged 51 years and the other aged 59 years. Genetic sequencing methods identified no pathogenic sequence changes between the twins in each pair. Conclusions and Relevance Our findings challenge the traditional view of BAV as a condition with an entirely autosomal dominant inheritance pattern and emphasize the variability of penetrance of both BAV and thoracic aortic aneurysm as well as the variability of the association of the 2 conditions. Continued work to elucidate the genetic basis may lead to the refinement of risk stratification for affected patients and relatives.
The effect of the DISC1 Ser704Cys polymorphism on striatal dopamine synthesis capacity: an [18F]‐DOPA PET study

Abstract Whilst the role of the Disrupted‐in‐Schizophrenia 1 (DISC1) gene in the aetiology of major mental illnesses is debated, the characterization of its function lends it credibility as a candidate. A key aspect of this functional characterization is the determination of the role of common non‐synonymous polymorphisms on normal variation within these functions. The common allele (A) of the DISC1 single‐nucleotide polymorphism (SNP) rs821616 encodes a serine (ser) at the Ser704Cys polymorphism, and has been shown to increase the phosphorylation of extracellular signal‐regulated protein Kinases 1 and 2 (ERK1/2) that stimulate the phosphorylation of tyrosine hydroxylase, the rate‐limiting enzyme for dopamine biosynthesis. We therefore set out to test the hypothesis that human ser (A) homozygotes would show elevated dopamine synthesis capacity compared with cysteine (cys) homozygotes and heterozygotes (TT and AT) for rs821616. [18F]‐DOPA positron emission tomography (PET) was used to index striatal dopamine synthesis capacity as the influx rate constant Kicer in healthy volunteers DISC1 rs821616 ser homozygotes (N = 46) and healthy volunteers DISC1 rs821616 cys homozygotes and heterozygotes (N = 56), matched for age, gender, ethnicity and using three scanners. We found DISC1 rs821616 ser homozygotes exhibited a significantly higher striatal Kicer compared with cys homozygotes and heterozygotes (P = 0.012) explaining 6.4% of the variance (partial &eegr;2 = 0.064). Our finding is consistent with its previous association with heightened activation of ERK1/2, which stimulates tyrosine hydroxylase activity for dopamine synthesis. This could be a potential mechanism mediating risk for psychosis, lending further credibility to the fact that DISC1 is of functional interest in the aetiology of major mental illness.
Comparative-effectiveness research--implications of the Federal Coordinating Council's report.

Despite a plethora of diagnostic and treatment options, practical information that can guide health care choices for an individual patient are often elusive, and the resultant clinical uncertainty is an important factor driving regional variations in clinical practice. Clinicians and patients need to know not only that a treatment works on average but also which interventions work best for specific types of patients. Comparative patient-centered information is essential to translating new discoveries into better health outcomes, accelerating the application of beneficial innovations, and delivering the right treatment to the right patient at the right time.1 The American Recovery and Reinvestment .
Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors

Photoreceptors have depolarized resting potentials that stimulate calcium‐dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca2+ dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole‐cell recordings from light‐adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post‐synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca2+ influx by lowering extracellular Ca2+, by application of Cd2+ and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca2+. We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd2+ or by increased intracellular Ca2+ buffering in rods, but not in cones, that were voltage clamped at −70 mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post‐synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca2+‐independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran‐conjugated pHrodo. Spontaneous release in rods occurred more frequently at non‐ribbon sites than evoked release events. The function of Ca2+‐independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise.