Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary Voiding as a Tool to Reduce Radiation Exposure in the Nuclear Stress Lab

Nuclear stress testing is being increasingly justified in the cardiovascular risk stratification of patients. Radiation is an important consideration, and attempts to minimize exposure should be implemented. Efficiency and cost effectiveness are cornerstones in the delivery of quality patient care and should also be considered when implementing change. Methods: We studied 88 consecutive patients who presented to our stress lab for pharmacologic nuclear stress testing. A single-day rest-and-stress protocol with low-level exercise was used for all patients. After the stress portion of the examination, we measured Geiger counter activity above the bladder area to establish a baseline. Patients were then allowed to void, and repeat measurements were taken. Results: We detected a 16.9% reduction from baseline radiation levels above the bladder area after voiding. Conclusion: Urinary voiding is a simple, cost-effective strategy at reducing radiation exposure in the nuclear stress lab.
NLRP12 Attenuates Inflammatory Bone Loss in Experimental Apical Periodontitis

Apical periodontitis is an inflammatory disorder that results from the host immune response to microbial infection through the dental pulp, leading to alveolar bone destruction. The nod-like receptor 12 (NLRP12) is an atypical intracellular sensor of the NLR family that is involved in the negative regulation of several inflammatory conditions and also osteoclastogenesis. However, the role of NLRP12 in the regulation of immune response and bone loss induced by bacterial infection remains unclear. Here we investigated the development of apical periodontitis in wild-type (WT) and NLRP12 knockout (NLRP12–/–) mice by using micro–computed tomography together with histological, immunohistochemical, and molecular analyses. We found that NLRP12–/– mice are highly susceptible to apical periodontitis induced by bacterial infection, which is associated with an elevated infiltration of neutrophils and macrophages, periapical lesion extension, and alveolar bone destruction. Furthermore, NLRP12–/– mice showed a high expression of inflammatory cytokines (Il1b, Il6, and Tnfa) and the osteoclastogenic markers (Rankl and Acp5) in the periapical tissues. Consistent with this observation, NLRP12–/– mice showed an increased number of tartrate-resistant acid phosphatase–positive cells lining the apical periodontitis site, which was associated with augmented expression of the osteoclast effector genes, Ctsk and Mmp9. Mechanistically, NLRP12-deficient preosteoclasts showed elevated IκB-α degradation and p65 phosphorylation when stimulated with receptor activator of nuclear factor (NF)–κB ligand (RANKL). Similarly, increased IκB-α degradation was observed in the periapical tissue of NLRP12–/– mice. Furthermore, our in vitro study showed that preosteoclasts from NLRP12–/– mice exhibited higher RANKL-induced osteoclastogenesis, which was synergistically amplified by interleukin-1β and tumor necrosis factor α (mimicking an inflammatory periapical milieu). In conclusion, our data show that NLRP12 exhibits a protective role in the periapical bone destruction by attenuating inflammation and osteoclastogenesis through negative regulation of the NF-κB pathway.
Effect of quercetin on the echocardiographic parameters of left ventricular diastolic function in patients with gout and essential hypertension.

OBJECTIVE Introduction: Gout is associated closely with an increased risk of cardiovascular (CV) events including heart failure. The aim: Improvement of treating patients with gout and essential hypertension (EH) by applying course therapy of quercetin of the echocardiographic parameters of the left ventricular diastolic function. PATIENTS AND METHODS Materials and methods: 84 male patients with gout and EH. The main group consists of 43 patients who have performed treatment with quercetin and a comparative group of 41 patients who were performed treatment without quercetin. RESULTS Results: In patients with gout in combination with EH, the addition of quercetin to antihypertensive and urate-lowering treatment have a protective effect on cardiac diastolic function (the baseline-adjusted changes during 12 months were significantly lower in the quercetin group than in the comparative group for E/e' (-0,41± 0,01 vs. -0,08 ± 0,01, p = 0,001) and LV mass index, g/m2 (-3,28 ± 0,02 vs. -2,04 ± 0,03, p = 0,02). Also this combination contributed to faster and more pronounced achievement of the target level of uric acid (reduction by 33,7%), normalize renal function (the rate of glomerular filtration, ml/min/1,73 m2 level increase by 13,3%) and also had a cumulative antihypertensive effect (reduction of systolic blood pressure by 5,5% and diastolic blood pressure by 3,6%) without increasing the dose or adding new antihypertensive drugs. CONCLUSION Conclusion: adding quercetin to antihypertensive and urate-lowering regimens for 12 months in patients with gout and EH improve echocardiographic parameter of diastolic function left ventricular, purine metabolism, renal function and additional normalize blood pressure.
Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis

Fatigue is one of the most common symptoms in multiple sclerosis (MS), with a major impact on patients’ quality of life. Currently, treatment proceeds by trial and error with limited success, probably due to the presence of multiple different underlying mechanisms. Recent neuroscientific advances offer the potential to develop tools for differentiating these mechanisms in individual patients and ultimately provide a principled basis for treatment selection. However, development of these tools for differential diagnosis will require guidance by pathophysiological and cognitive theories that propose mechanisms which can be assessed in individual patients. This article provides an overview of contemporary pathophysiological theories of fatigue in MS and discusses how the mechanisms they propose may become measurable with emerging technologies and thus lay a foundation for future personalised treatments.
Feasibility of a Therapist-Supported, Mobile Phone–Delivered Online Intervention for Depression: Longitudinal Observational Study

Background Depression is a very common condition that impairs functioning and is often untreated. More than 60% of the treatments for depressive disorder are administered in primary care settings by care providers who lack the time and expertise to treat depression. To address this issue, we developed Ascend, a therapist-supported, mobile phone–delivered 8-week intervention administered at the Meru Health Online Clinic in Finland. Objective We conducted two pilot studies to examine the feasibility of the Ascend intervention, specifically, dropout rates, daily practice, weekly group chat use, and changes in depression symptoms. We also explored whether daily practice and weekly group chat use were associated with changes in depression symptoms. Methods A total of 117 Finnish adults with elevated depressive symptoms enrolled in Ascend, a program that included daily cognitive behavioral and mindfulness meditation exercises delivered through a mobile phone app, anonymous group chat with other users, and chat/phone access to a licensed therapist. Eight weekly themes were delivered in a fixed, sequential format. Depression symptoms were measured at baseline, every second week during the intervention, immediately after the intervention, and 4 weeks after completion of the intervention. Data were analyzed using intent-to-treat repeated-measures analysis of variance and linear regression models. Results For studies 1 and 2, we observed dropout rates of 27% and 15%, respectively, decreasing daily practice and group chat use, and decreased depression symptoms from baseline to immediately and 4 weeks after the intervention (P<.001). We found that both more daily practice and chat group use predicted the occurrence of fewer depressive symptoms at 4 weeks postintervention (Study 1: ∆R2 =.38, P=.004 and ∆R2 =.38, P=.002, respectively; Study 2: ∆R2 =.16, P<.001 and ∆R2 =.08, P=.002, respectively). Conclusions This therapist-supported, mobile phone–delivered treatment for depression is feasible and associated with reduced depression symptoms. Design features that enhance daily practice and group chat use are areas of future investigation. Validation of these results using a controlled study design is needed to establish the evidence base for the Ascend intervention.
A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone

Background: Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown. In this study, we investigated the role of Irf6 in craniofacial bone development using comparative analyses between wild‐type (WT) and Irf6‐null littermate mice. Results: Immunostaining revealed the expression of IRF6 in hypertrophic chondrocytes, osteocytes, and bone matrix of craniofacial tissues. Histological analysis of Irf6‐null mice showed a remarkable reduction in the number of lacunae, embedded osteocytes in matrices, and a reduction in mineralization during bone formation. These abnormalities may explain the decreased craniofacial bone density detected by micro‐CT, loss of incisors, and mandibular bone abnormality of Irf6‐null mice. To validate the autonomous role of IRF6 in bone, extracted primary osteoblasts from calvarial bone of WT and Irf6‐null pups showed no effect on osteoblastic viability and proliferation. However, a reduction in mineralization was detected in Irf6‐null cells. Conclusions: Altogether, these findings suggest an autonomous role of Irf6 in regulating bone differentiation and mineralization. Developmental Dynamics 248:221‐232, 2019. © 2019 Wiley Periodicals, Inc.
Oxidative Stress and Antioxidant Biomarkers in Clinical and Experimental Models of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH.
Integrated Management for the Reduction of Calonectria Infections in Ornamental Nurseries.

Chemical control represents the main effective strategy for managing Calonectria diseases in ornamental nurseries. The occurrence of fungicide-resistant strains and the European Directive on "Sustainable Use of Pesticides" has forced ornamental plant growers to establish effective integrated pest management strategies to control Calonectria infections. Here, three nursery experiments were performed to detect the best combinations of fungicides and biological control agents (BCA) to control both leaf spot, caused by six Calonectria spp. on bottlebrush and metrosideros, and stem rot, caused by Calonectria morganii on Dodonaea plants. Overall, the cyprodinil + fludioxonil mixture alone or combined with bioformulates containing Bacillus, Trichoderma, and Streptomyces spp. provided the best performance in reducing leaf spot and stem rot caused by Calonectria spp. , followed by the mixture of boscalid + pyraclostrobin. Although BCA alone provided disease suppression significantly lower than the controls in most cases, these treatments were, on average, the least effective in controlling Calonectria infections. Otherwise, there were no significant increases in efficacy with fungicides plus BCA over fungicides alone. Thus, the application of boscalid + pyraclostrobin and cyprodinil + fludioxonil mixtures may also be used in large-scale applications to reduce Calonectria diseases because they effectively managed leaf and stem infections. Our comprehensive research applied previously acquired information on Calonectria disease management in nurseries, resulting in important data that affects integrated plans to fight these pathogens in accordance with European legislation.
Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl‐CoA availability and increases plant polyphenol synthesis

In recent years microorganisms have been engineered towards synthesizing interesting plant polyphenols such as flavonoids and stilbenes from glucose. Currently, the low endogenous supply of malonyl‐CoA, indispensable for plant polyphenol synthesis, impedes high product titers. Usually, limited malonyl‐CoA availability during plant polyphenol production is avoided by supplementing fatty acid synthesis‐inhibiting antibiotics such as cerulenin, which are known to increase the intracellular malonyl‐CoA pool as a side effect. Motivated by the goal of microbial polyphenol synthesis being independent of such expensive additives, we used rational metabolic engineering approaches to modulate regulation of fatty acid synthesis and flux into the tricarboxylic acid cycle (TCA cycle) in Corynebacterium glutamicum strains capable of flavonoid and stilbene synthesis. Initial experiments showed that sole overexpression of genes coding for the native malonyl‐CoA‐forming acetyl‐CoA carboxylase is not sufficient for increasing polyphenol production in C. glutamicum. Hence, the intracellular acetyl‐CoA availability was also increased by reducing the flux into the TCA cycle through reduction of citrate synthase activity. In defined cultivation medium, the constructed C. glutamicum strains accumulated 24 mg·L −1 (0.088 mM) naringenin or 112 mg·L −1 (0.49 mM) resveratrol from glucose without supplementation of phenylpropanoid precursor molecules or any inhibitors of fatty acid synthesis.
Hip Osteoarthritis and Physical Workload: Influence of Study Quality on Risk Estimations—A Meta-Analysis of Epidemiological Findings

In this paper, we critically evaluate the quality of epidemiological evidence on hip osteoarthritis and workload published so far. The influence of study quality on risk estimations was analyzed in sensitivity meta-analyses and meta-regression analyses. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases and current reviews. All studies were assessed on the basis of study design, defined quality scores, and relevant confounders considered. In total, 34 suitable studies were identified for critical evaluation. Of these, 20 are prevalence studies and 14 incidence studies. Strong heterogeneity is observed in study design, quality level, and estimated exposure parameters. A consistent positive association between heavy physical workload and hip osteoarthritis was observed only among the male populations, not among the female populations. In general, cohort studies provided lower effect estimates than cross-sectional and population-based case-control studies. Studies with high quality scores also produced lower effect estimates than studies with low quality scores. Consideration of BMI as a confounder in published studies also yielded lower effect estimates than studies without consideration of BMI as a confounder. Our analyses indicate that high-quality studies of the association between occupational workload and hip osteoarthritis provide lower effect estimates than studies of lower quality.
Central Line Care

&NA; Empowering patients to prevent infection and injury via EPIC2 BACKGROUND: Central line‐associated bloodstream infections (CLABSIs) are associated with an increased risk of mortality, prolonged hospitalizations, and inflated cost of care. Patients in the hematology‐oncology specialty unit are at greater risk of developing CLABSIs because of their immunocompromised state and high number of central line (CL) days. OBJECTIVES: The aim of the EPIC2 project was to reduce CLABSI rates on a hematology‐oncology specialty unit with historically high CLABSI rates despite prior quality improvement efforts. METHODS: EPIC2 used the theory of planned behavior as the framework for changing patient behavior and was based on evidence from the Partners in Your Care© handwashing study that successfully engaged patients to hold healthcare professionals accountable. FINDINGS: The three‐month preintervention average CLABSI rate was 5.69. During the intervention period, the average rate was 3.24. This accounted for a 43% reduction in CLABSIs. Participants in the EPIC2 project reported feeling empowered to speak up against improper CL care.
High-Throughput Rapid and Inexpensive Assay for Quantitative Determination of Low Cell-Density Yeast Cultures

A procedure for microbial cell density determination with a high-throughput densitometric assay was developed to allow a precise quantification of both free and sessile cells, such as those of a biofilm, with a large range from low to high cell densities. Densitometry was chosen because it allows fast, rapid and cost-effective measures; it is non-disruptive; and has an easy learning curve. The method setup, and the further validation, was carried out with strains of Candida albicans, C. tropicalis and C. parapsilosis. Equations were developed at the level of the single strains, of the three species and finally a general one applicable to all three species. In the cross validation, with strains absent from the training set, the method was shown to be robust and flexible. The best results were obtained with species specific equations, although the global equation performed almost as well in terms of correlation between real and estimated density values. In all cases, a correlation around 0.98 between effective and predicted density was obtained with figures ranging from 102 to 108 cells mL−1. The entire analytical part of the procedure can be accomplished with a MS Excel macro provided free of charge.
Impact of Carbamide Peroxide Whitening Agent on Dentinal Collagen

Carbamide peroxide (CP) is widely used as a tooth-whitening agent in self-administered tooth-bleaching products. In this study, the effects of 5% and 10% CP on dentinal collagen structure and chemical properties were evaluated in vitro. Thirty-five intact teeth were exposed to 2 whitening protocols (2 or 4 h daily) with either 5% or 10% CP gel for 1 wk. Shade changes before and after the whitening protocol were captured colorimetrically using a spectroshade. Collagen scaffold models and demineralized dentine disc samples were prepared and exposed to CP droplets (5% or 10%). Structural changes were investigated using electron microscopy. Finally, mineralized dentine disc samples were prepared postbleaching to assess chemical changes resulting from CP exposure in dentinal collagen using Raman spectroscopy. Results showed a difference in tooth shade when exposed to 5% and 10% CP whitening protocols, with a significantly (P ≤ 0.01) greater change reported for the 10% CP/4-h group. Imaging of the collagen scaffold model following exposure to CP showed a gelatinization process indicating that the free radical by-products from CP are able to disrupt the quaternary structure of noncrosslinked collagen. The most significant damage on the collagen scaffold was seen for the 10% CP exposure for 4 h. Imaging of the demineralized discs displayed the same glassy amorphous layer appearance as found in the collagen scaffold. Raman spectra of the mineralized dentine discs showed a significant decrease (P ≤ 0.01) in the integrated area of amide I and amide III values in the 4 test groups following CP application. Amide I was more affected as both the exposure time and concentration of CP increased. Despite the claimed safety of whitening agents, this in vitro study concludes that even low concentrations of CP result in a deleterious change in dentinal collagen.
Gαi2 Signaling Regulates Inflammasome Priming and Cytokine Production by Biasing Macrophage Phenotype Determination

Macrophages exist as innate immune subsets that exhibit phenotypic heterogeneity and functional plasticity. Their phenotypes are dictated by inputs from the tissue microenvironment. G-protein–coupled receptors are essential in transducing signals from the microenvironment, and heterotrimeric Gα signaling links these receptors to downstream effectors. Several Gαi-coupled G-protein–coupled receptors have been implicated in macrophage polarization. In this study, we use genetically modified mice to investigate the role of Gαi2 on inflammasome activity and macrophage polarization. We report that Gαi2 in murine bone marrow–derived macrophages (BMDMs) regulates IL-1β release after activation of the NLRP3, AIM2, and NLRC4 inflammasomes. We show this regulation stems from the biased polarity of Gαi2 deficient (Gnai2−/−) and RGS-insensitive Gαi2 (Gnai2G184S/G184S) BMDMs. We determined that although Gnai2G184S/G184S BMDMs (excess Gαi2 signaling) have a tendency toward classically activated proinflammatory (M1) phenotype, Gnai2−/− BMDMs (Gαi2 deficient) are biased toward alternatively activated anti-inflammatory (M2) phenotype. Finally, we find that Gαi2-deficient macrophages have increased Akt activation and IFN-β production but defects in ERK1/2 and STAT3 activation after LPS stimulation. Gαi2-deficient macrophages also exhibit increased STAT6 activation after IL-4 stimulation. In summary, our data indicates that excess Gαi2 signaling promotes an M1 macrophage phenotype, whereas Gαi2 signaling deficiency promotes an M2 phenotype. Understanding Gαi2-mediated effects on macrophage polarization may bring to light insights regarding disease pathogenesis and the reprogramming of macrophages for the development of novel therapeutics.