Miracle-dz/UniFAR-FTUs huggingface dataset:
The opposing contribution of neurotrophin-3 and nerve growth factor to orofacial heat hyperalgesia in rats

Supplemental Digital Content is available in the text. It has been proposed that neurotrophin-3 acts in a manner that is opposed to nerve growth factor, especially in the modulation of heat hyperalgesia. Injury to the constriction of the infraorbital nerve (CION) is a well-established model of trigeminal neuropathic pain that leads to robust heat, cold, and mechanical hyperalgesia. Here, we assessed the effect of local neurotrophin-3 treatment on CION-induced hyperalgesia, and we examined some mechanisms related to the effect of neurotrophin-3. Neurotrophin-3 (1 µg/50 µl) injected into the upper lip of CION rats caused a significant and long-lasting reduction of CION-induced heat hyperalgesia, but failed to affect cold and mechanical hyperalgesia. Increased levels of neurotrophin-3 were detected in the injured nerve at the time point that represents the peak of heat hyperalgesia. The anti-hyperalgesic effect of neurotrophin-3 was markedly reduced in the presence of an antagonist of TrkA receptors (K-252a, 1 μg/50 μl). Moreover, association of lower doses of neurotrophin-3 with an antibody anti-nerve growth factor resulted in a synergistic anti-hyperalgesic effect in CION rats. Local injection of nerve growth factor (3 µg/50 µl) or the TRPV1 agonist capsaicin (1 μg/50 μl), but not neurotrophin-3 injection (1 µg/50 µl), resulted in long-lasting facial heat hyperalgesia, which was both significantly reduced by previous neurotrophin-3 local treatment. In conclusion, we suggest that neurotrophin-3 is a potent modulator of facial heat hyperalgesia, which may exert an inhibitory influence on the trkA pathway. Neurotrophin-3 treatment may represent a promising approach, especially in pain conditions associated with increased levels of nerve growth factor.
Tailoring Antimicrobial Susceptibility Testing to Individual Species of Coagulase-Negative Staphylococci: Next Up, Staphylococcus epidermidis

Accurate detection of methicillin resistance among staphylococci is vital for patient care. Methicillin resistance is most commonly mediated by acquisition of the mecA gene, which encodes an altered penicillin binding protein, PBP2a. Application of phenotypic methods to detect mecA-mediated beta-lactam resistance in staphylococci is becoming more complex as species-specific differences are identified among coagulase-negative staphylococci (CoNS). ABSTRACT Accurate detection of methicillin resistance among staphylococci is vital for patient care. Methicillin resistance is most commonly mediated by acquisition of the mecA gene, which encodes an altered penicillin binding protein, PBP2a. Application of phenotypic methods to detect mecA-mediated beta-lactam resistance in staphylococci is becoming more complex as species-specific differences are identified among coagulase-negative staphylococci (CoNS). Previously, interpretative criteria and antimicrobial susceptibility testing (AST) methods specific to the CoNS group were used to evaluate Staphylococcus epidermidis. A manuscript by S. N. Naccache, K. Callan, C. -A. D. Burnham, M. A. Wallace, et al. (J Clin Microbiol 57:e00961-19, 2019, https://doi.org/10.1128/JCM.00961-19) details experiments revealing that S. epidermidis, the most common clinically isolated CoNS, requires tailored use of previously described methods and interpretive criteria to reliably identify the presence of mecA-mediated methicillin resistance.
The Effect of Prolonged Postoperative Antibiotic Administration on the Rate of Infection in Patients Undergoing Posterior Spinal Surgery Requiring a Closed-Suction Drain: A Randomized Controlled Trial.

BACKGROUND Closed-suction drains are frequently used following posterior spinal surgery. The optimal timing of antibiotic discontinuation in this population may influence infection risk, but there is a paucity of evidence. The aim of this study was to determine whether postoperative antibiotic administration for 72 hours (24 hours after drain removal as drains were removed on the second postoperative day) decreases the incidence of surgical site infection compared with postoperative antibiotic administration for 24 hours. METHODS Patients undergoing posterior thoracolumbar spinal surgery managed with a closed-suction drain were prospectively randomized into 1 of 2 groups of postoperative antibiotic durations: (1) 24 hours, or (2) 24 hours after drain removal (72 hours). Drains were discontinued on the second postoperative day. The duration of antibiotic administration was not blinded. All subjects received a single dose of preoperative antibiotics, as well as intraoperative antibiotics if the surgical procedure lasted >4 hours. The primary outcome was the rate of complicated surgical site infection (deep or organ or space) within 1 year of the surgical procedure. RESULTS The trial was terminated at an interim analysis, when 552 patients were enrolled, for futility with respect to the primary outcome. In this study, 282 patients were randomized to postoperative antibiotics for 24 hours and 270 patients were randomized to postoperative antibiotics for 72 hours. A complicated infection developed in 17 patients (6.0%) in the 24-hour group and in 14 patients (5.2%) in the 72-hour group (p = 0.714). The superficial infection rate did not differ between the groups (p = 0.654): 9.6% in the 24-hour group compared with 8.1% in the 72-hour group. Patients in the 72-hour group had a median hospital stay that was 1 day longer (p < 0.001). At 1 year, patient-rated outcomes including leg and back pain and physical and mental functioning were not different between the groups. CONCLUSIONS The extension of postoperative antibiotics for 72 hours, when a closed-suction drain is required, was not associated with a reduction in the rate of complicated surgical site infection after posterior thoracolumbar spinal surgery. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of Levels of Evidence.
Shape-shifting structured lattices via multimaterial 4D printing

Significance Thin shape-shifting structures are often limited in their ability to morph into complex and doubly curved shapes. Such transformations require both large in-plane expansion or contraction gradients and control over extrinsic curvature, which are hard to achieve with single materials arranged in simple architectures. We solve this problem by 4-dimensional printing of multiple materials in heterogeneous lattice designs. Our material system provides a platform that achieves in-plane growth and out-of-plane curvature control for 4-material bilayer ribs. The lattice design converts this into large growth gradients, which lead to complex, predictable 3-dimensional (3D) shape changes. We demonstrate this approach with a hemispherical antenna that shifts resonant frequency as it changes shape and a flat lattice that transforms into a 3D human face. Shape-morphing structured materials have the ability to transform a range of applications. However, their design and fabrication remain challenging due to the difficulty of controlling the underlying metric tensor in space and time. Here, we exploit a combination of multiple materials, geometry, and 4-dimensional (4D) printing to create structured heterogeneous lattices that overcome this problem. Our printable inks are composed of elastomeric matrices with tunable cross-link density and anisotropic filler that enable precise control of their elastic modulus (E) and coefficient of thermal expansion (α). The inks are printed in the form of lattices with curved bilayer ribs whose geometry is individually programmed to achieve local control over the metric tensor. For independent control of extrinsic curvature, we created multiplexed bilayer ribs composed of 4 materials, which enables us to encode a wide range of 3-dimensional (3D) shape changes in response to temperature. As exemplars, we designed and printed planar lattices that morph into frequency-shifting antennae and a human face, demonstrating functionality and geometric complexity, respectively. Our inverse geometric design and multimaterial 4D printing method can be readily extended to other stimuli-responsive materials and different 2-dimensional (2D) and 3D cell designs to create scalable, reversible, shape-shifting structures with unprecedented complexity.
Risk factors for axillary lymph node metastases in clinical stage T1-2N0M0 breast cancer patients

Abstract Axillary lymph node metastasis (ALNM) is commonly the earliest detectable clinical manifestation of breast cancer when distant metastasis emerges. This study aimed to explore the influencing factors of ALNM and develop models that can predict its occurrence preoperatively. Cases of sonographically visible clinical stage T1-2N0M0 breast cancers treated with breast and axillary surgery at West China Hospital were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to evaluate associations between ALNM and variables. Decision tree analyses were performed to construct predictive models using the C5.0 packages. Of the 1671 tumors, 541 (32.9%) showed axillary lymph node positivity on final surgical histopathologic analysis. In multivariate logistic regression analysis, tumor size (P < .001), infiltration of subcutaneous adipose tissue (P < .001), infiltration of the interstitial adipose tissue (P = .031), and tumor quadrant locations (P < .001) were significantly correlated with ALNM. Furthermore, the accuracy in the decision tree model was 69.52%, and the false-negative rate (FNR) was 74.18%. By using the error-cost matrix algorithm, the FNR significantly decreased to 14.75%, particularly for nodes 5, 8, and 13 (FNR: 11.4%, 9.09%, and 14.29% in the training set and 18.1%,14.71%, and 20% in the test set, respectively). In summary, our study demonstrated that tumor lesion boundary, tumor size, and tumor quadrant locations were the most important factors affecting ALNM in cT1-2N0M0 stage breast cancer. The decision tree built using these variables reached a slightly higher FNR than sentinel lymph node dissection in predicting ALNM in some selected patients.
The Novel Phosphodiesterase 9A Inhibitor BI 409306 Increases Cyclic Guanosine Monophosphate Levels in the Brain, Promotes Synaptic Plasticity, and Enhances Memory Function in Rodents

N-methyl-d-aspartate (NMDA) receptor–dependent long-term potentiation (LTP) is an established cellular model underlying learning and memory, and involves intracellular signaling mediated by the second messenger cyclic guanosine monophosphate (cGMP). As phosphodiesterase (PDE)9A selectively hydrolyses cGMP in areas of the brain related to cognition, PDE9A inhibitors may improve cognitive function by enhancing NMDA receptor-dependent LTP. This study aimed to pharmacologically characterize BI 409306, a novel PDE9A inhibitor, using in vitro assays and in vivo determination of cGMP levels in the brain. Further, the effects of BI 409306 on synaptic plasticity evaluated by LTP in ex vivo hippocampal slices and on cognitive performance in rodents were also investigated. In vitro assays demonstrated that BI 409306 is a potent and selective inhibitor of human and rat PDE9A with mean concentrations at half-maximal inhibition (IC50) of 65 and 168 nM. BI 409306 increased cGMP levels in rat prefrontal cortex and cerebrospinal fluid and attenuated a reduction in mouse striatum cGMP induced by the NMDA-receptor antagonist MK-801. In ex vivo rat brain slices, BI 409306 enhanced LTP induced by both weak and strong tetanic stimulation. Treatment of mice with BI 409306 reversed MK-801-induced working memory deficits in a T-maze spontaneous-alternation task and improved long-term memory in an object recognition task. These findings suggest that BI 409306 is a potent and selective inhibitor of PDE9A. BI 409306 shows target engagement by increasing cGMP levels in brain, facilitates synaptic plasticity as demonstrated by enhancement of hippocampal LTP, and improves episodic and working memory function in rodents. SIGNIFICANCE STATEMENT This preclinical study demonstrates that BI 409306 is a potent and selective PDE9A inhibitor in rodents. Treatment with BI 409306 increased brain cGMP levels, promoted long-term potentiation, and improved episodic and working memory performance in rodents. These findings support a role for PDE9A in synaptic plasticity and cognition. The potential benefits of BI 409306 are currently being investigated in clinical trials.
Subsidence and perioperative periprosthetic fractures using collarless hydroxyapatite-coated stem for displaced femoral neck fractures according to Dorr type

Background: Hydroxyapatite (HA)-coated stem has been introduced to decrease complications and eventually achieve quicker implant ingrowth and long-term stability. The aim of this study was to determine subsidence rate and incidence of perioperative periprosthetic fracture (PPF) of uncemented collarless Corail stem for displaced femoral neck fractures according to Dorr type. Methods: A retrospective review of plain radiographs and clinical data was carried out to identify consecutive patients who underwent uncemented hip hemiarthroplasty using collarless HA-coated Corail stem between March 2010 and August 2014. The risk of subsidence and PPF according to Dorr type was evaluated. Results: Dorr types A, B, and C were found in 66 (median age 74, 29.7%), 107 (median age 77, 48.2%), and 49 (median age 80, 22.1%) cases, respectively. Subsidence of stem occurred in eight (3.6%) cases. Dorr type had significant relationship (p < 0.05) with subsidence. Type C canals had higher rates of subsidence. PPFs occurred in 11 (5.0%) cases without showing significant difference among Dorr types not significant (n.s.). Female gender was not influential on subsidence (n.s.) and PPF (n.s.). Conclusion: Dorr type C had higher risk of subsidence when using uncemented collarless HA-coated stem. Dorr canal type had no bearing on risk of PPFs. Women did not have significantly higher risk of both subsidence and PPFs compared to men. A collarless fully HA-coated Corail stem had 3.6% of radiological subsidence and 5.0% of PPF risk.
Adaptive features of innate immune cells and their relevance to graft rejection.

PURPOSE OF REVIEW Allograft rejection involves both innate and adaptive immune cells, and the adaptive immune cells have dominated transplant studies for decades. Recent studies have identified surprising new features for the innate immune cells, including memory recall responses, which may have significant implications in further improvement of transplant outcomes. RECENT FINDINGS Transplant survival is excellent in the short-term, but the long-term graft outcomes are not so, and most grafts are continuously lost to chronic rejection in the clinic. In both animal models and clinical settings, graft loss to chronic rejection is often dominated by innate immune cells, especially macrophages and natural killer (NK) cells in the grafts. Recent studies suggest that innate immune cells can acquire features of adaptive cells in that they either directly sense allogeneic nonself or become 'trained' in the allogeneic milieu, where they show features of memory recall responses. In certain models, targeting the adaptive features of such innate immune cells can promote long-term allograft survival. These findings may open new therapeutic opportunities in promoting transplant survival in the clinic. SUMMARY The discovery of donor specificity and memory recall responses of certain innate immune cells, which are prominently featured in chronic allograft rejection, may open novel therapeutic opportunities in transplantation, as well as in treatment of cancers and autoimmune diseases.
Epilepsy and lifestyle behaviors related to bone health

Adults aged 50 years and older with epilepsy face an increased risk of fracture associated both with age and with the use of antiepileptic drugs. Lifestyle behaviors, such as physical activity and calcium and vitamin D intake, have been found to be beneficial to bone health. The aim of this study is to investigate these osteoprotective behaviors in people aged 50 years and older with and without epilepsy.
Efficacy and safety of empagliflozin in older patients in the EMPA-REG OUTCOME® trial.

OBJECTIVE The risks of cardio-renal complications of diabetes increase with age. In the EMPA-REG OUTCOME® trial, empagliflozin reduced cardiovascular (CV) mortality by 38% in patients with type 2 diabetes (T2D) and CV disease. Here we compare outcomes with empagliflozin in older patients in EMPA-REG OUTCOME. METHODS Patients with T2D and CV disease were randomised to empagliflozin 10 or 25 mg, or placebo plus standard of care. In post hoc analyses, risks of 3-point major adverse CV events (3P-MACE: composite of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke), CV death, hospitalisation for heart failure, all-cause mortality, all-cause hospitalisation and incident/worsening nephropathy were evaluated for empagliflozin versus placebo by baseline age (<65, 65 to <75, ≥75 years). Adverse events (AEs) were analysed descriptively. RESULTS Effect of empagliflozin on all outcomes was consistent across age categories (P ≥ 0.05 for interactions) except 3P-MACE. The 3P-MACE hazard ratios (HRs) were 1.04 (95% confidence interval [CI] 0.84, 1.29), 0.74 (0.58, 0.93) and 0.68 (0.46, 1.00) in patients aged <65, 65 to <75, and ≥75 years, respectively (P = 0.047 for treatment-by-age group interaction). Corresponding CV death HRs were 0.72 (95% CI 0.52, 1.01), 0.54 (0.37, 0.79) and 0.55 (0.32, 0.94), respectively (P = 0.484 for treatment-by-age group interaction). Across age categories, empagliflozin AEs reflected its known safety profile. Rates of bone fractures, renal AEs and diabetic ketoacidosis were similar between empagliflozin and placebo across age categories. CONCLUSIONS In the EMPA-REG OUTCOME trial, empagliflozin reduced risks of CV mortality, heart failure and renal outcomes, supporting its cardio-renal benefits in older patients.
Speech-in-speech perception, nonverbal selective attention, and musical training.

Speech is more difficult to understand when it is presented concurrently with a distractor speech stream. One source of this difficulty is that competing speech can act as an attentional lure, requiring listeners to exert attentional control to ensure that attention does not drift away from the target. Stronger attentional control may enable listeners to more successfully ignore distracting speech, and so individual differences in selective attention may be one factor driving the ability to perceive speech in complex environments. However, the lack of a paradigm for measuring nonverbal sustained selective attention to sound has made this hypothesis difficult to test. Here we find that individuals who are better able to attend to a stream of tones and respond to occasional repeated sequences while ignoring a distractor tone stream are also better able to perceive speech masked by a single distractor talker. We also find that participants who have undergone more musical training show better performance on both verbal and nonverbal selective attention tasks, and this musician advantage is greater in older participants. This suggests that one source of a potential musician advantage for speech perception in complex environments may be experience or skill in directing and maintaining attention to a single auditory object. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Self-Reference enhances memory for multi-element events judged likely to happen in young and older adults

ABSTRACT We investigated whether the strategy of self-reference can benefit memory for multi-element events, a kind of relational memory that is relatively less studied but highly relevant to daily life. Young and older adults imagined different person-object-location events with reference to themselves and two famous others (i.e., George Clooney and Oprah Winfrey), rated the likelihood that each event would happen, and then completed incidental memory tests on different pairs of elements within the event. We found that self-reference enhanced memory for object-location and person-object pairs in both age groups. Such self-reference effects were observed consistently only for events rated as likely to happen. There was also an overall memory advantage for the higher-likelihood events, which did not differ between young and older adults. Further, the self-reference effects were not correlated with memory functioning in either age group. Retrieval of within-event associations showed a significant level of dependency, which did not differ as a function of reference condition or likelihood category. These findings highlight the ways in which self-reference and prior knowledge improve relational memory, and suggest that the advantage of self-reference is not attributable to increased dependence of elements within complex events.
Impact of resistance training sets performed until muscular failure with different loads on intraocular pressure and ocular perfusion pressure

Purpose: The aim of this article is to investigate the acute effects of bench press sets leading to muscular failure with different loads on intraocular pressure and ocular perfusion pressure. Study design: A randomized experimental study. Methods: Seventeen physically active young men performed four resistance training sets of bench press to muscular failure against different relative loads (65% one-repetition maximum vs 75% one-repetition maximum vs 85% one-repetition maximum vs 95% one-repetition maximum). Intraocular pressure was measured before and immediately after the execution of each of the four sets, and ocular perfusion pressure was also assessed before and after physical effort. Results: We found that intraocular pressure increased after reaching muscular failure (p < 0.001, ƞ²= 0.52), being also dependent on the interaction load × point of measure (p < 0.001, ƞ²= 0.33). Our data demonstrated that higher intraocular pressure increases were found when participants performed the bench press exercise against heavier loads, showing statistical significance for the 75% one-repetition maximum (p = 0.020, d = –0.63, mean change = 0.9 mmHg), 85% one-repetition maximum (p = 0.035, d = –0.56, mean change = 1.4 mmHg), and 95% one-repetition maximum (p < 0.001, d = –1.36, mean change = 2.9 mmHg) relative loads. For its part, ocular perfusion pressure showed a reduction after exercise (p = 0.009, ƞ²= 0.35), being these changes independent on the load used. Conclusion: Bench press exercise leading to muscular failure provokes an acute intraocular pressure rise, with greater changes when heavier loads are used. Ocular perfusion pressure exhibited an acute reduction after exercise; however, its clinical relevance seems to be insignificant (lower to 4%). We argue that the use of heavy loads, when training to muscular failure, should be discouraged in order to avoid acute intraocular pressure fluctuations. Future studies should corroborate the generalizability of these findings in glaucoma patients.