Miracle-dz/UniFAR-FTUs huggingface dataset:
Verbal Communication With Providers Improves Acceptance of Antimicrobial Stewardship Interventions

tion is the necessity of data collection and its analysis. The inclusion of a dedicated project manager allows for ongoing critical data analysis as well as interdisciplinary coordination across departments to improve the efficiency of the program while broadening the impact and scope of the ASP to improve patient care. We encourage other institutions interested in developing an ASP to reach out to their quality department for individuals trained in process improvement and program implementation.
Oral and masticatory rehabilitation using osseointegrated dental implants after resective treatment of multicystic ameloblastoma in the lower jaw with a fibula graft

Ameloblastoma is an aggressive odontogenic tumor which typically occurs between third and fourth decade of life that often needs resective approach. Immediate reconstruction may show better results. The treatment of multicystic ameloblastoma in the mandible being a rare case that occurred in the late second decade of life, which was surgically removed along with the affected teeth with safety margins, and the region was immediately reconstructed using a vascularized graft, removed from the fibula. Its integration, in combination with osseointegrated dental implants and fixed implant-supported prostheses, restored chewing function and esthetics. After 6 years from fibular graft and 24 months of dental implants, an excellent outcome was observed, with oral health and normal functions properly restored, and the immediate reconstruction of the mandible in resective cases, associated with oral rehabilitation with dental implants, may be considered a suitable treatment option.
Dynamic energy dependency of Chlamydia trachomatis on host cell metabolism during intracellular growth: Role of sodium-based energetics in chlamydial ATP generation

Chlamydia trachomatis is an obligate intracellular human pathogen responsible for the most prevalent sexually-transmitted infection in the world. For decades C. trachomatis has been considered an “energy parasite” that relies entirely on the uptake of ATP from the host cell. The genomic data suggest that C. trachomatis respiratory chain could produce a sodium gradient that may sustain the energetic demands required for its rapid multiplication. However, this mechanism awaits experimental confirmation. Moreover, the relationship of chlamydiae with the host cell, in particular its energy dependence, is not well understood. In this work, we are showing that C. trachomatis has an active respiratory metabolism that seems to be coupled to the sodium-dependent synthesis of ATP. Moreover, our results show that the inhibition of mitochondrial ATP synthesis at an early stage decreases the rate of infection and the chlamydial inclusion size. In contrast, the inhibition of the chlamydial respiratory chain at mid-stage of the infection cycle decreases the inclusion size but has no effect on infection rate. Remarkably, the addition of monensin, a Na+/H+ exchanger, completely halts the infection. Altogether, our data indicate that chlamydial development has a dynamic relationship with the mitochondrial metabolism of the host, in which the bacterium mostly depends on host ATP synthesis at an early stage, and at later stages it can sustain its own energy needs through the formation of a sodium gradient.
Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial

Background: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. Methods: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. Results: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (−21.0% versus −11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (−39.5% versus −21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA− groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (−22%), intrahepatic (−29%), and intrapericardial (−11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, −6.67cm2; 95% confidence interval, −14.8 to −0.45) compared with PA−. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. Conclusions: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT01530724.
Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells

Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein–coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA, pull-downs, and surface plasmon resonance) provided direct evidence of the interaction between staphylococcal enterotoxin E and LAMA2. Through its G4 domain, LAMA2 mediated the LCK-independent T cell activation by these toxins. Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor type because the selective antagonist NPS 2143 inhibited superantigen-induced T cell activation in vitro and delayed the effects of toxic shock syndrome in vivo. Collectively, our data identify LAMA2 as a target of antagonists of staphylococcal superantigens to treat toxic shock syndrome.
ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death

Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-&bgr; signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death.
Cross-subject classification of cognitive loads using a recurrent-residual deep network

The problem of automatically learning temporal and spectral feature representations for EEG signals has been intensely studied in the last years. However, most solutions are focused on extracting representations used for training classifiers in particular subjects. This is not well suitable for applications involving several subjects, since it requires high computing times and costs at labeling data and training classifiers for each new subject involved. To address this problem, we propose an improvement of a deep neural network architecture, using residual layers and Gated Recurrent Units (GRU), able to extract feature representations for “cross-subject” classification. Our architecture, called RecResNet, achieved a better accuracy (0.907±0.124) and F-measure (0.896±0.148) than other baseline methods, when applied to the classification of four levels of cognitive loads using 13 subjects.
Deoxyribonuclease-Inhibitory Antibodies in Systemic Lupus erythematosus

Deoxyribonucleases (DNases) are key enzymes for digesting DNA. Abnormalities in the function of these enzymes may contribute to the development of anti-DNA antibodies in systemic lupus erythematosus (SLE). In this study, we used bovine DNase 1-coated ELISA plates to screen anti-DNase antibodies in SLE patients. About 62% of the sera of SLE patients (63/101) were positive for anti-DNase antibodies compared to only 8% of normal controls (8/98). A positive correlation was also found between the concentrations of anti-DNase and anti-DNA antibodies in sera of SLE patients. Affinity-purified anti-DNase immunoglobulin G (IgG) from pooled sera of SLE patients bound to bovine DNase as well as DNA. A synthetic peptide, corresponding to the catalytic site of DNase, was able to completely inhibit the binding of anti-DNase IgG to DNase. In addition to bovine DNase, the anti-DNase IgG also bound to and inhibited the enzymatic activities of DNase present in streptococcal supernatants and human urine. Immunization of lupus-prone NZB/NZW mice with bovine DNase enhanced the production of anti-DNase and DNA antibodies, and accelerated the occurrence of proteinuria. Taken together, these results suggest that DNase-inhibitory antibodies which recognize a conserved epitope near the catalytic site of DNase may act in the pathogenesis of SLE.
Adaptation of Campylobacter jejuni to biocides used in the food industry affects biofilm structure, adhesion strength, and cross-resistance to clinical antimicrobial compounds

Abstract The emergence of biocide-adapted Campylobacter jejuni strains that developed into biofilms and their potential to develop clinical resistance to antimicrobial compounds was studied. C. jejuni was grown in sub-lethal concentrations of five biocides used in the food industry. C. jejuni exhibited adaptation to these biocides with increased minimum inhibitory concentrations. The 3-D structures of the biofilms produced by the biocide-adapted cells were investigated by atomic force microscopy (AFM). The results revealed marked variability in biofilm architecture, including ice-crystal-like structures. Adaptation to the biocides enhanced biofilm formation, with significant increases in biovolume, surface coverage, roughness, and the surface adhesion force of the biofilms. Adaptation to commercial biocides induced resistance to kanamycin and streptomycin. This study suggests that the inappropriate use of biocides may lead to cells being exposed to them at sub-lethal concentrations, which can result in adaptation of the pathogens to the biocides and a subsequent risk to public health.
The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.
Cholinergic excitation in mouse primary vs. associative cortex: region‐specific magnitude and receptor balance

Cholinergic stimulation of the cerebral cortex is essential for tasks requiring attention; however, there is still some debate over which cortical regions are required for such tasks. There is extensive cholinergic innervation of both primary and associative cortices, and transient release of acetylcholine (ACh) is detected in deep layers of the relevant primary and/or associative cortex, depending on the nature of the attention task. Here, we investigated the electrophysiological effects of ACh in layer VI, the deepest layer, of the primary somatosensory cortex, the primary motor cortex, and the associative medial prefrontal cortex. Layer VI pyramidal neurons are a major source of top‐down modulation of attention, and we found that the strength and homogeneity of their direct cholinergic excitation was region‐specific. On average, neurons in the primary cortical regions showed weaker responses to ACh, mediated by a balance of contributions from both nicotinic and muscarinic ACh receptors. Conversely, neurons in the associative medial prefrontal cortex showed significantly stronger excitation by ACh, mediated predominantly by nicotinic receptors. The greatest diversity of responses to ACh was found in the primary somatosensory cortex, with only a subset of neurons showing nicotinic excitation. In a mouse model with attention deficits only under demanding conditions, cholinergic excitation was preserved in primary cortical regions but not in the associative medial prefrontal cortex. These findings demonstrate that the effect of ACh is not uniform throughout the cortex, and suggest that its ability to enhance attention performance may involve different cellular mechanisms across cortical regions.
Understanding the functional role of microRNA‐214‐3p in atherosclerosis for the identification of novel targeted therapies to prevent or reverse endothelial cell dysfunction and stimulate autophagy

The original article by Jing Wang and collaborators, entitled “MicroRNA-214-3p: A Link between Autophagy and Endothelial Cell Dysfunction in Atherosclerosis”, brings new data concerning molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis. In this issue of Acta Physiologica, the authors concluded that microRNA-214-3p (miR-214-3p) controls oxidized low-density lipoprotein (ox-LDL)-induced autophagy in human umbilical vein endothelial cells (HUVECs) by regulating intracellular levels of autophagy-related protein 5 (ATG5), and may have a relevant role in the pathogenesis of atherosclerosis. This study was done through in vivo and in vitro experiments conducted in ApoE-/- mice supplied with high fat diet (HFD) as atherosclerosis model and HUVECs. In vivo experiments, ATG5, ATG12 and miR-214-3p levels were analysed in the purified CD31+ endothelial cells from mouse aorta. Interesting, prediction of the binding between miR-214-3p and 3′-UTR of ATG5 mRNA was performed by bioinformatics analyses. In vitro experiments, HUVECs were transfected in order to modulate miR-214-3p and stimulated with ox-LDL to induce a stress-repairing autophagic process. The authors showed in their experimental study three very important aspects: (1) in atherosclerotic mouse model, they identified an inverse correlation between miR-214-3p and ATG5 and ATG12; (2) in young HUVEC, they found ox-LDL induced autophagy as evidenced by the increases in ATG5, ATG12, and microtubule-associated protein 1 light chain 3 (LC3B) protein levels with a simultaneously decreased SQSTM1/p62 protein level, and miR-214-3p overexpression reduced autophagy; (3) in old HUVECs, inhibition of the miR-214-3p increased their protective autophagy response to the ox-LDL stimulus, as evaluated by autophagic protein analysis, LC3B immunofluorescence assay, and transmission electron microscopy (TEM) 1 This article is protected by copyright. All rights reserved.
Predicting Difficult Intubation in Emergency Department by Intubation Assessment Score

Background The difficult intubation is associated with failure of emergency tracheal intubation. This study aimed to develop and validate a model for predicting difficult intubation in emergency department (ED). Methods A cross-sectional study was conducted in the ED. We collected data from all consecutive adult patients who underwent emergency tracheal intubation. Patients were excluded if they were intubated by low experience intubator. The difficult intubation was defined by grade III or IV of Cormack and Lehane classification. We used multivariable regression model to identify significant predictors of difficult intubation and weighted points proportional to the beta coefficient values. The ability to discriminate was quantified by using the area under receiver operating characteristics curve (AuROC). The bootstrapping method was used to validate the performance. Results A total of 1,212 intubations were analyzed. One hundred and fifty-seven intubations were enrolled in difficult intubation group. Five independence predictors were identified, and each was assigned a number of points proportional to its beta coefficient: male gender (one), large tongue (two), limit mouth opening (two), poor neck mobility (two), and presence of obstructed airway (three). Intubation assessment score model was created and applied to all subjects. The AuROC was 0.81 (95% confidence interval (CI): 0.77 - 0.85) for the development dataset, and 0.80 (95% CI: 0.76 - 0.85) for the validation dataset. We defined three risk groups: low risk (zero to one points), intermediate risk (two to three points), and high risk (above three points), and the difficult intubation rate was 4.7%, 22.5%, and 53.6%, respectively. Conclusions Intubation assessment score model was constructed from patients’ simple characteristics and performed well in predicting difficult intubation and can discriminate between with and without difficult intubation.
The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes

Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.