Miracle-dz/UniFAR-FTUs huggingface dataset:
Excitability of Rat Superficial Dorsal Horn Neurons Following a Neonatal Immune Challenge

Previous studies have shown that neonatal exposure to a mild inflammatory challenge, such as lipopolysaccharide (LPS, Salmonella enteriditis) results in altered pain behaviors later in life. To further characterize the impact of a neonatal immune challenge on pain processing, we examined the excitability of superficial dorsal horn (SDH) neurons following neonatal LPS exposure and subsequent responses to noxious stimulation at three time-points during early postnatal development. Wistar rats were injected with LPS (0.05 mg/kg i.p.) or saline on postnatal days (PNDs) 3 and 5, and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection into the plantar hindpaw, animals were euthanized (Ketamine, 100 mg/kg i.p.) and transverse slices from the lumbosacral spinal cord were prepared. Whole-cell patch-clamp recordings were made from SDH neurons (KCH3SO4-based internal, 22–24°C) on the ipsi- and contralateral sides of the spinal cord. Depolarising current steps were injected into SDH neurons to categorize action potential (AP) discharge. In both saline- and LPS-treated rats we observed age-related increases the percentage of neurons exhibiting tonic-firing, with concurrent decreases in single-spiking, between PND 7 and 22. In contrast, neonatal exposure to LPS failed to alter the proportions of AP discharge patterns at any age examined. We also assessed the subthreshold currents that determine AP discharge in SDH neurons. The rapid outward potassium current, IAr decreased in prevalence with age, but was susceptible to neonatal LPS exposure. Peak IAr current amplitude was greater in ipsilateral vs. contralateral SDH neurons from LPS-treated rats. Spontaneous excitatory synaptic currents (sEPSCs) were recorded to assess network excitability. Age-related increases were observed in sEPSC frequency and time course, but not peak amplitude, in both saline- and LPS-treated rats. Furthermore, sEPSC frequency was higher in ipsilateral vs. contralateral SDH neurons in LPS-treated animals. Taken together, these data suggest a neonatal immune challenge does not markedly affect the intrinsic properties of SDH neurons, however, it can increase the excitability of local spinal cord networks via altering the properties of rapid A-type currents and excitatory synaptic connections. These changes, made in neurons within spinal cord pain circuits, have the capacity to alter nociceptive signaling in the ascending pain pathway.
Apparent Diffusion Coefficient Levels and Neurodevelopmental Outcome in Fetuses with Brain MR Imaging White Matter Hyperintense Signal

BACKGROUND AND PURPOSE: One of the perplexing findings of fetal brain MR imaging is white matter T2 hyperintense signal. The aims of our study were initially to determine the main etiologies associated with white matter T2 hyperintense signal, then to examine whether the different etiologies have different ADC values, and, last, to assess the association of white matter T2 hyperintense signal with developmental outcome. MATERIALS AND METHODS: This was a prospective cohort study of 44 MR imaging scans of fetal brains obtained for suspected brain pathologies at a tertiary medical center during 2011–2015. Clinical data were collected from electronic medical charts. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes. Neurodevelopmental assessments were performed with the Vineland Adaptive Behavior Scales II. RESULTS: Half of the cases of MRI hyperintense T2 signal of the fetal brain were associated with congenital cytomegalovirus infection. The other half were mainly idiopathic. Thus, the study group was divided to subgroups positive and negative for cytomegalovirus. Both groups had hyperintense signal in the temporal lobe. The group positive for cytomegalovirus had involvement of the parietal lobe. Only this group had increased ADC values in the temporal and parietal lobes. There was no association between the neurodevelopment outcome and the etiologies or ADC values. CONCLUSIONS: T2 hyperintense signal in fetal brain MRI associated with positive cytomegalovirus infection has increased ADC values in the temporal and parietal lobes, suggestive of brain edema in these areas. However, the association between this finding and neurodevelopment outcome requires further evaluation.
Improving systematic rabies surveillance in Cameroon: A pilot initiative and results for 2014-2016

Canine rabies is endemic in Cameroon, but human rabies exposures and cases are likely underreported because of inadequate surveillance. In 2014, the surveillance network in the West region of Cameroon was reinforced by introducing a new anti-rabies center, a framework for data collection and evaluation, provisions for sample collecting and laboratory confirmation, and training for health professionals. The objective of this observational cohort study was to describe the incidence and characteristics of reported exposures and human and animal rabies cases following this reinforcement of the existing rabies surveillance system. The surveillance network consisted of local, regional, and national health and veterinary authorities in 11 of the 20 West region districts, and was completely integrated within the existing national rabies surveillance network. Animal exposures and suspected rabies exposures, the suspected rabid animals involved, and laboratory confirmation of human and animal rabies cases were recorded in a centralized information database. Between January 2014 and June 2016, the network recorded 1340 animal exposure cases for an overall incidence rate of 38.2 animal exposures per 100,000 people, four confirmed rabies-positive animals, and one confirmed human rabies case out of four clinically suspected cases. In contrast, 62 animal exposures and an overall incidence rate of 6.1 exposures per 100,000 people were reported for the West region districts not participating in the reinforced surveillance. Of the 925 animal exposure victims for whom a detailed case report form was completed, 703 were considered to be at risk of rabies and only 428 (61%) of these received any post-exposure prophylaxis in the form of rabies vaccine. Obstacles encountered within the network included low rates of animal sample submission and animal follow-up by veterinarians. Reinforced rabies surveillance in the West region of Cameroon has provided the most accurate estimate of the region’s disease and exposure burdens to date, and indicates that animal exposures are substantially underreported. The reinforced network also signaled that greater access to post-exposure prophylaxis is needed. Integration of regions not covered by the surveillance network and efforts to improve engagement of veterinary services will be needed to reveal the true burden of rabies in Cameroon.
Efficiency of Emergency Physicians: Insights from an Observational Study using EHR Log Files

Abstract Objective With federal mandates and incentives since the turn of this decade, electronic health records (EHR) have been widely adopted and used for clinical care. Over the last several years, we have seen both positive and negative perspectives on its use. Using an analysis of log files of EHR use, we investigated the nature of EHR use and their effect on an emergency department's (ED) throughput and efficiency. Methods EHR logs of time spent by attending physicians on EHR-based activities over a 6-week period (n = 2,304 patients) were collected. For each patient encounter, physician activities in the EHR were categorized into four activities: documentation, review, orders, and navigation. Four ED-based performance metrics were also captured: door-to-provider time, door-to-doctor time, door-to-disposition time, and length of stay (LOS). Association between the four EHR-based activities and corresponding ED performance metrics were evaluated. Results We found positive correlations between physician review of patient charts, and door-to-disposition time (r = 0.43, p < 0.05), and with LOS (r = 0.48, p < 0.05). There were no statistically significant associations between any of the other performance metrics and EHR activities. Conclusion The results highlight that longer time spent on reviewing information on the EHR is potentially associated with decreased ED throughput efficiency. Balancing these competing goals is often a challenge of physicians, and its implications for patient safety is discussed.
Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi

To understand the diversity of scorpion venom, RNA from venomous glands from a sawfinger scorpion, Serradigitus gertschi, of the family Vaejovidae, was extracted and used for transcriptomic analysis. A total of 84,835 transcripts were assembled after Illumina sequencing. From those, 119 transcripts were annotated and found to putatively code for peptides or proteins that share sequence similarities with the previously reported venom components of other species. In accordance with sequence similarity, the transcripts were classified as potentially coding for 37 ion channel toxins; 17 host defense peptides; 28 enzymes, including phospholipases, hyaluronidases, metalloproteases, and serine proteases; nine protease inhibitor-like peptides; 10 peptides of the cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 protein superfamily; seven La1-like peptides; and 11 sequences classified as “other venom components”. A mass fingerprint performed by mass spectrometry identified 204 components with molecular masses varying from 444.26 Da to 12,432.80 Da, plus several higher molecular weight proteins whose precise masses were not determined. The LC-MS/MS analysis of a tryptic digestion of the soluble venom resulted in the de novo determination of 16,840 peptide sequences, 24 of which matched sequences predicted from the translated transcriptome. The database presented here increases our general knowledge of the biodiversity of venom components from neglected non-buthid scorpions.
Pharmacodynamic Analysis of Daptomycin-Treated Enterococcal Bacteremia: It Is Time to Change the Breakpoint.

Background Currently, there is debate that the daptomycin susceptibility breakpoint (i.e., minimum inhibitory concentration, MIC, ≤4 mg/L) is inappropriate for application to serious enterococcal infections. Observational data support prescription of high doses (>8 mg/kg/day) in the treatment of bacteremia. Pharmacodynamic targets associated with positive patient outcomes, however, remain undefined. Methods Data were pooled from observational studies assessing outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antibiotic with activity against enterococci and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of 30-day survival was identified by classification and regression tree (CART) analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs. Results Of 114 patients that received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. Stratifying the cohort by severity of illness, a fAUC/MIC >27.43 was associated with survival in low-acuity (N=77) patients (68.9 versus 37.5%, p=0.006), which remained significant (p=0.026) after adjusting for infection source and immunosuppression. The PTA for a 6 mg/kg/day dose was 1.5-5.5% when MIC=4 mg/L (i.e., daptomycin-susceptible) and 91.0-97.9% when MIC=1 mg/L. Conclusions For enterococcal bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of re-evaluation of the current susceptibility breakpoint.
Does Free-Text Information in Falls Incident Reports Assist to Explain How and Why the Falls Occurred in a Hospital Setting?

Objective The aim of this study was to explore whether information captured in falls reports in incident management systems could be used to explain how and why the falls occurred, with a view to identifying whether such reports can be a source of subsequent learnings that inform practice change. Methods An analysis of prospectively collected falls incident reports found in the incident management systems from eight Western Australian hospitals during a stepped-wedge cluster-randomized controlled trial. The falls reported occurred in a cohort of older hospital patients (mean age = 82 y) on rehabilitation wards. Data coded from free-text comments in the incident reports were analyzed using deductive content analysis. Results In the 493 analyzed falls incident reports, qualitative information describing aspects of the fall that clarified the patient, staff, and environment-related contributory factors was consistently low. Reports infrequently contained information about patients’ and staff’s call bell use behaviors (13%–19% of reports), fidelity of implementation of the care plan (8%) or environment-related factors such as bed settings (20%), and presence of clutter at the fall location (1%). The patients’ account of the fall was present in less than 50% of reports, with an absence of concurrent text, which explained whether patient cognitive impairment was the reason for not obtaining this first-person account of the incident. Conclusions Falls reports in hospital incident management systems may not capture adequate information to explain how and why falls occur. This could limit creation of effective feedback loops to drive quality improvement efforts and targeted practice change.
Selection and Plasmid Transfer Underlie Adaptive Mutation in Escherichia coli

In the Cairns–Foster adaptive mutation system, a +1 lac frameshift mutant of Escherichia coli is plated on lactose medium, where the nondividing population gives rise to Lac+ revertant colonies during a week under selection. Reversion requires the mutant lac allele to be located on a conjugative F′lac plasmid that also encodes the error-prone DNA polymerase, DinB. Rare plated cells with multiple copies of the mutant F′lac plasmid initiate the clones that develop into revertants under selection. These initiator cells arise before plating, and their extra lac copies allow them to divide on lactose and produce identical F′lac-bearing daughter cells that can mate with each other. DNA breaks can form during plasmid transfer and their recombinational repair can initiate rolling-circle replication of the recipient plasmid. This replication is mutagenic because the amplified plasmid encodes the error-prone DinB polymerase. A new model proposes that Lac+ revertants arise during mutagenic over-replication of the F′lac plasmid under selection. This mutagenesis is focused on the plasmid because the cell chromosome replicates very little. The outer membrane protein OmpA is essential for reversion under selection. OmpA helps cells conserve energy and may stabilize the long-term mating pairs that produce revertants.
Cellular immune response to human influenza viruses differs between H1N1 and H3N2 subtypes in the ferret lung

Seasonal influenza virus infections cause yearly epidemics which are the source of a significant public health burden worldwide. The ferret model for human influenza A virus (IAV) is widely used and has several advantages over other animal models such as comparable symptomology, similar receptor distribution in the respiratory tract to humans and the ability to be infected with human isolates without the need for adaptation. However, a major disadvantage of the model has been a paucity of reagents for the evaluation of the cellular immune response. Investigation of T-cell mediated immunity in ferrets is crucial to vaccine development and efficacy studies. In this study we have used commercially produced antibodies to ferret interferon gamma (IFN-γ) allowing us to reliably measure influenza-specific IFN-γ as a marker of the cellular immune response using both enzyme-linked immunospot (ELISpot) and enzyme-linked immunosorbent (ELISA) techniques. Here we demonstrate the application of these tools to evaluate cellular immunity in ferrets infected with clinically relevant seasonal H1N1 and H3N2 IAV subtypes at equivalent doses. Using small heparinised blood samples we were able to observe the longitudinal influenza-specific IFN-γ responses of ferrets infected with both seasonal subtypes of IAV and found a notable increase in influenza-specific IFN-γ responses in circulating peripheral blood within 8 days post-infection. Both seasonal strains caused a well-defined pattern of influenza-specific IFN-γ responses in infected ferrets when compared to naïve animals. Additionally, we found that while the influenza specific IFN-γ responses found in peripheral circulating blood were comparable between subtypes, the influenza specific IFN-γ responses found in lung lymphocytes significantly differed. Our results suggest that there is a distinct difference between the ability of the two seasonal influenza strains to establish an infection in the lung of ferrets associated with distinct signatures of acquired immunity.
Assessment and pathophysiology of pain in cardiac surgery

Analysis of the problem of surgical pain is important in view of the fact that the success of surgical treatment depends largely on proper pain management during the first few days after a cardiosurgical procedure. Postoperative pain is due to intraoperative damage to tissue. It is acute pain of high intensity proportional to the type of procedure. The pain is most intense during the first 24 hours following the surgery and decreases on subsequent days. Its intensity is higher in younger subjects than elderly and obese patients, and preoperative anxiety is also a factor that increases postoperative pain. Ineffective postoperative analgesic therapy may cause several complications that are dangerous to a patient. Inappropriate postoperative pain management may result in chronic pain, immunosuppression, infections, and less effective wound healing. Understanding and better knowledge of physiological disorders and adverse effects resulting from surgical trauma, anesthesia, and extracorporeal circulation, as well as the development of standards for intensive postoperative care units are critical to the improvement of early treatment outcomes and patient comfort.
Real-life results of switching from preserved to preservative-free artificial tears containing hyaluronate in patients with dry eye disease

Background Dry eye disease (DED) is a chronic, multifactorial disease of the ocular surface leading to discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface. Aim The aim of this study was to assess the clinical benefit of a switch from preserved to preservative-free artificial tears (ATs) containing hyaluronate in patients with DED. Materials and methods This is a nationwide, multicenter, noninterventional, and transversal observational survey. Results The mean age was 51.0±15.4 years, ranging from 6 to 96 years. The majority (61.4%) was female. The mean Ocular Surface Disease Index (OSDI) before the switch was surprisingly high at 56.0±23.5, and 73.0% of the patients had superficial punctate keratitis (SPK). The mean duration of use of preserved ATs before the switch was 15.8±12.1 months. OSDI scores and the presence of SPK correlated with the patients’ ages but were independent of the duration of treatment with the preserved AT. The patients using ATs containing “soft” or “vanishing” preservatives presented exactly the same clinical pattern (level of OSDI and frequency of SPK) as those using ATs containing classical preservatives such as benzalkonium chloride (BAK). After switching to preservative-free AT containing hyaluronate (Hyabak®), the OSDI of 97.0% of the patients improved, decreasing from an average of 56.0 to an average of 28.2, with 23% of patients reporting a normal value of OSDI. The SPK frequency as well improved dramatically, with a frequency of positive fluorescein staining dropping from 73% to 46.1% of patients. A total of 94.0% of the patients considered that they preferred being treated with the preservative-free AT. Conclusion In patients suffering from DED and treated with a preserved AT, switching to a preservative-free AT provides clinical benefit by decreasing the severity of DED and reducing the prevalence of SPK, even after only 3 weeks of daily use of the preservative-free AT.
The state of the art in semantic relatedness: a framework for comparison

Abstract Semantic relatedness (SR) is a form of measurement that quantitatively identifies the relationship between two words or concepts based on the similarity or closeness of their meaning. In the recent years, there have been noteworthy efforts to compute SR between pairs of words or concepts by exploiting various knowledge resources such as linguistically structured (e.g. WordNet) and collaboratively developed knowledge bases (e.g. Wikipedia), among others. The existing approaches rely on different methods for utilizing these knowledge resources, for instance, methods that depend on the path between two words, or a vector representation of the word descriptions. The purpose of this paper is to review and present the state of the art in SR research through a hierarchical framework. The dimensions of the proposed framework cover three main aspects of SR approaches including the resources they rely on, the computational methods applied on the resources for developing a relatedness metric, and the evaluation models that are used for measuring their effectiveness. We have selected 14 representative SR approaches to be analyzed using our framework. We compare and critically review each of them through the dimensions of our framework, thus, identifying strengths and weaknesses of each approach. In addition, we provide guidelines for researchers and practitioners on how to select the most relevant SR method for their purpose. Finally, based on the comparative analysis of the reviewed relatedness measures, we identify existing challenges and potentially valuable future research directions in this domain.