Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of mitochondrial NADP(H)-transhydrogenase expression in macrophages exacerbates atherosclerosis in hypercholesterolemic mice.

The atherosclerosis prone LDL receptor knockout mice (Ldlr -/-, C57BL/6J background)carry a deletion of the NADP(H)-transhydrogenase gene (Nnt) encoding the mitochondrial enzyme that catalyzes NADPH synthesis. Here we hypothesize that both increased NADPH consumption (due to increased steroidogenesis) and decreased NADPH generation (due to Nnt deficiency) in Ldlr-/- mice contribute to establish a macrophage oxidative stress and increase atherosclerosis development. Thus, we compared peritoneal macrophages and liver mitochondria from three C57BL/6J mice lines: Ldlr and Nnt double mutant, single Nnt mutant and wild-type. We found increased oxidants production in both mitochondria and macrophages according to a gradient: double mutant > single mutant > wild-type. We also observed a parallel upregulation of mitochondrial biogenesis (PGC1a, TFAM and respiratory complexes levels) and inflammatory (iNOS, IL6 and IL1b) markers in single and double mutant macrophages. When exposed to modified LDL, the single and double mutant cells exhibited significant increases in lipid accumulation leading to foam cell formation, the hallmark of atherosclerosis. Nnt deficiency cells showed upregulation of CD36 and downregulation of ABCA1 transporters what may explain lipid accumulation in macrophages. Finally, Nnt wild-type bone marrow transplantation into LDLr-/- mice resulted in reduced diet induced atherosclerosis. Therefore, Nnt plays a critical role in the maintenance of macrophage redox, inflammatory and cholesterol homeostasis, which is relevant for delaying the atherogenesis process.
Unscarred uterine rupture: a retrospective study

Background: Uterine rupture is a catastrophic obstetrical emergency associated with significant feto-maternal morbidity and mortality. Many risk factors have been identified, as well as wide range of clinical presentations. The objective of the study was to analyse the incidence and predisposing factors of unscarred uterine rupture and to determine maternal and fetal outcome. Methods: Retrospective analysis of unscarred uterine rupture cases was conducted at the Department of Obstetrics and Gynecology, RIMS, Imphal from June 2012 to June 2014. Results: Our case series comprised of 13 cases with unscarred uterine rupture incidence of 0.057%. Out of these, 69.2% were unbooked cases. Majority of the cases were para 2-3. Most of the rupture (76.9%) occurred during 2nd stage of labour. The lower segment uterine rupture was the most common site of rupture (30.8%) Maternal and perinatal mortality were 30.8% and 53.8%, respectively. Sub-total hysterectomy done in 87.5% cases. Conclusions: Rupture uterus is a high risk category of patients. An unscarred uterus can undergo rupture even without risk factors. The patients with mismanaged labour, grand multiparas and obstructed prolonged labour must be managed by proper trained personnel and in tertiary care centre in order to avoid the morbidity or mortality.
Locus Coeruleus Norepinephrine Drives Stress-Induced Increases in Basolateral Amygdala Firing and Impairs Extinction Learning

Stress impairs extinction learning, and these deficits depend, in part, on stress-induced norepinephrine (NE) release in the basolateral amygdala (BLA). For example, systemic or intra-BLA administration of propranolol reduces the immediate extinction deficit (IED), an impairment in extinction learning that occurs when extinction trials are administered soon after fear conditioning. Here, we explored whether locus coeruleus (LC)-NE regulates stress-induced changes in spike firing in the BLA and consequent extinction learning impairments. Rats were implanted with recording arrays in the BLA and, after recovery from surgery, underwent a standard auditory fear conditioning procedure. Fear conditioning produced an immediate and dramatic increase in the spontaneous firing of BLA neurons that persisted (and in some units, increased further) up to an hour after conditioning. This stress-induced increase in BLA firing was prevented by systemic administration of propranolol. Conditioning with a weaker footshock caused smaller increases in BLA firing rate, but this could be augmented by chemogenetic activation of the LC. Conditioned freezing in response to a tone paired with a weak footshock was immune to the IED, but chemogenetic activation of the LC before the weak conditioning protocol increased conditioned freezing behavior and induced an IED; this effect was blocked with intra-BLA infusions of propranolol. These data suggest that stress-induced activation of the LC increases BLA spike firing and causes impairments in extinction learning. Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with stress- and trauma-related disorders. SIGNIFICANCE STATEMENT Patients with post-traumatic stress disorder (PTSD) show heightened amygdala activity; elevated levels of stress hormones, including norepinephrine; and are resistant to the extinction of fear memories. Here, we show that stress increases basolateral amygdala (BLA) spike firing. This could be attenuated by systemic propranolol and mimicked by chemogenetic activation of the locus coeruleus (LC), the source of forebrain norepinephrine (NE). Finally, we show that LC-NE activation is sufficient to produce extinction deficits, and this is blocked by intra-BLA propranolol. Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with PTSD and related disorders.
Assessing different diagnostic tests for gastroesophageal reflux disease: a systematic review and network meta-analysis

Background: The aim of the current systematic review and network meta-analysis (NMA) was to assess the diagnostic characteristics of the gastroesophageal reflux disease questionnaire (GERDQ), proton-pump inhibitor (PPI) test, baseline impedance, mucosal impedance, dilated intercellular spaces (DIS), salivary pepsin, esophageal pH/pH impedance monitoring and endoscopy for gastroesophageal reflux disease (GERD). Methods: We searched PubMed and the Cochrane Controlled Trial Register database (from inception to 10 April 2018) for studies assessing the diagnostic characteristics of the GERDQ, PPI test, baseline impedance, mucosal impedance, DIS, or salivary pepsin and esophageal pH/pH impedance monitoring/endoscopy in patients with GERD. Direct pairwise comparison and a NMA using Bayesian methods under random effects were performed. We also assessed the ranking probability. Results: A total of 40 studies were identified. The NMA found no significant difference among the baseline impedance, mucosal impedance, and esophageal pH/pH impedance monitoring and endoscopy in terms of both sensitivity and specificity. It was also demonstrated that the salivary pepsin detected by the Peptest device had comparable specificity to esophageal pH/pH impedance monitoring and endoscopy. Results of ranking probability indicated that esophageal pH/pH impedance monitoring and endoscopy had highest sensitivity and specificity, followed by mucosal impedance and baseline impedance, whereas GERDQ had the lowest sensitivity and PPI test had the lowest specificity. Conclusions: In a systematic review and NMA of studies of patients with GERD, we found that baseline impedance and mucosal impedance have relatively high diagnostic performance, similar to esophageal pH/pH impedance monitoring and endoscopy.
Cardiopulmonary Bypass and Infant Vaccination Titers

A prospective study to assess how CPB affects vaccination status in infants undergoing congenital heart surgery. BrightcoveDefaultPlayer10.1542/6096746050001PEDS-VA_2019-1716 Video Abstract BACKGROUND: Infants with congenital heart disease remain vulnerable to potentially preventable pathogens. Although immunization can significantly reduce this risk, it is unknown how immunization status can be affected by cardiac surgery with cardiopulmonary bypass (CPB). The objective was to evaluate the effect of CPB on infant vaccination status after cardiac surgery. METHODS: We conducted a prospective observational study of patients between 2 and 14 months of age who had received at least their first round of infant vaccinations and who required cardiac surgery with CPB. Antibody titers were measured before CPB and again the following morning. Demographic and surgical variables were assessed via regression methods for their effects on the change in titers. RESULTS: Among the 98 patients followed, there was no demonstrated difference between the pre- and postoperative values in regard to diphtheria, tetanus, polio 1, polio 3, or Haemophilus influenzae titers. Bordetella (1.03 vs 0.84, P < .001), and hepatitis B (log 2.10 vs 1.89, P = .001) titers did reduce after CPB but did not fall below the immunized threshold. Changes in antibody titers were not associated with time between immunization and surgery, age or weight at surgery, blood products administered, number of previous doses, time on CPB, or heterotaxy diagnosis for most of the vaccines. CONCLUSIONS: Infant vaccine antibody titers were minimally affected by CPB and not associated with any easily modifiable surgical variables. Although antibody titers are only 1 marker of immunity, deviation from the recommended vaccination schedule may be unnecessary for children requiring congenital heart surgery.
Validation of linear energy transfer computed in a Monte Carlo dose engine of a commercial treatment planning system

The relative biological effectiveness (RBE) of protons is highly variable and difficult to quantify. However, RBE is related to the local ionization density, which can be related to the physical measurable dose weighted linear energy transfer (LETD). The aim of this study was to validate the LETD calculations for proton therapy beams implemented in a commercially available treatment planning system (TPS) using microdosimetry measurements and independent LETD calculations (Open-MCsquare (MCS)). The TPS (RayStation v6R) was used to generate treatment plans on the CIRS-731-HN anthropomorphic phantom for three anatomical sites (brain, nasopharynx, neck) for a spherical target (Ø = 5 cm) with uniform target dose to calculate the LETD distribution. Measurements were performed at the University Medical Center Groningen proton therapy center (Proteus Plus, IBA) using a µ+-probe utilizing silicon on insulator microdosimeters capable of detecting lineal energies as low as 0.15 keV µm−1 in tissue. Dose averaged mean lineal energy depth-profiles were measured for 70 and 130 MeV spots in water and for the three treatment plans in water and an anthropomorphic phantom. The measurements were compared to the LETD calculated in the TPS and MCS independent dose calculation engine. D · was compared to D · LETD in terms of a gamma-index with a distance-to-agreement criteria of 2 mm and increasing dose difference criteria to determine the criteria for which a 90% pass rate was accomplished. Measurements of D · were in good agreement with the D · LETD calculated in the TPS and MCS. The 90% passing rate threshold was reached at different D · LETD difference criteria for single spots (TPS: 1% MCS: 1%), treatment plans in water (TPS: 3% MCS: 6%) and treatment plans in an anthropomorphic phantom (TPS: 6% MCS: 1%). We conclude that D · LETD calculations accuracy in the RayStation TPS and open MCSquare are within 6%, and sufficient for clinical D · LETD evaluation and optimization. These findings remove an important obstacle in the road towards clinical implementation of D · LETD evaluation and optimization of proton therapy treatment plans. Novelty and significance The dose weighed linear energy transfer (LETD) distribution can be calculated for proton therapy treatment plans by Monte Carlo dose engines. The relative biological effectiveness (RBE) of protons is known to vary with the LETD distribution. Therefore, there exists a need for accurate calculation of clinical LETD distributions. Previous LETD validations have focused on general purpose Monte Carlo dose engines which are typically not used clinically. We present the first validation of mean lineal energy measurements of the LETD against calculations by the Monte Carlo dose engines of the Raystation treatment planning system and open MCSquare.
Comparative study of the composition of cultivated, naturally grown Cordyceps sinensis, and stiff worms across different sampling years

Natural Cordyceps sinensis, which is a valuable anti-tumor, immunomodulatory, and antiviral agent in Asia, has been overexploited in recent years. Therefore, it is important for cultivated C. sinensis to be recognized in the market. In this research, the main components of entirely cultivated, naturally grown C. sinensis, and stiff worms across different sampling years were detected and compared by HPLC-MS and UV spectrometry. The results indicated that the mean levels of adenosine and cordycepin were significantly higher, whereas the mean levels of mannitol and polysaccharides were remarkably lower in the cultivated type than in the natural type. No distinct difference in the average soluble protein content was observed. The composition of the stiff worms was similar to that of the natural herb, except that the total soluble protein content was higher, and that of mannitol was lower. In addition, the ultraviolet absorption spectroscopy of the three types showed high similarity at 260 nm. This research indicates that the main nutritional composition of cultivated and natural C. sinensis is identical and that cultivated type can be used as an effective substitute.
Evaluation of dentinogenesis inducer biomaterials: an in vivo study

Abstract When exposure of the pulp to external environment occurs, reparative dentinogenesis can be induced by direct pulp capping to maintain pulp tissue vitality and function. These clinical situations require the use of materials that induce dentin repair and, subsequently, formation of a mineralized tissue. Objective: This work aims to assess the effect of tricalcium silicate cements and mineral trioxide aggregate cements, including repairing dentin formation and inflammatory reactions over time after pulp exposure in Wistar rats. Methodology: These two biomaterials were compared with positive control groups (open cavity with pulp tissue exposure) and negative control groups (no intervention). The evaluations were performed in three stages; three, seven and twenty-one days, and consisted of an imaging (nuclear medicine) and histological evaluation (H&E staining, immunohistochemistry and Alizarin Red S). Results: The therapeutic effect of these biomaterials was confirmed. Nuclear medicine evaluation demonstrated that the uptake of 99mTc-Hydroxymethylene diphosphonate (HMDP) showed no significant differences between the different experimental groups and the control, revealing the non-occurrence of differences in the phosphocalcium metabolism. The histological study demonstrated that in mineral trioxide aggregate therapies, the presence of moderate inflammatory infiltration was found after three days, decreasing during follow-ups. The formation of mineralized tissue was only verified at 21 days of follow-up. The tricalcium silicate therapies demonstrated the presence of a slight inflammatory infiltration on the third day, increasing throughout the follow-up. The formation of mineralized tissue was observed in the seventh follow-up day, increasing over time. Conclusions: The mineral trioxide aggregate (WhiteProRoot®MTA) and tricalcium silicate (Biodentine™) present slight and reversible inflammatory signs in the pulp tissue, with the formation of mineralized tissue. However, the exacerbated induction of mineralized tissue formation with the tricalcium silicate biomaterial may lead to the formation of pulp calcifications
PQR Model-based Micromechanical Analysis of Hysteresis Loops for Single Crystal Fatigue: Aspects of Multi-Axial Loading, Geometric Effects and Creep

The micromechanical theory of fatigue crack initiation, namely the PQR model with a gating mechanism proposed by Lin (1992), is systematically summarized and further generalized to arbitrary loading conditions which may occur in reality. All possible loading cases and slip mechanisms are considered for a FCC single crystal. The Schmid factors for both primary and secondary slip systems are presented. A 3D boundary element method is adopted to compute the stress influence coefficients for the residual stress field. The hysteresis loops, which are due to a general two phase sequential loading process, i.e., a uni-axial loading followed by a multi-axial loading applied by combined shear and axial loadings, are given to illustrate the fatigue development and demonstrate the proposed methodology. The results show that the two stage loading may increase the magnitudes of intrusion and extrusion. Subsequently the geometry influence for intrusion is studied. The effect of geometry variation caused by intrusion is taken into account through updating the stress influence coefficients as well as the applied resolved stress when intrusion grows. This process is continued until the saturated state of fatigue crack initiation is reached. Comparison of geometry influence on intrusion growth is shown as well. It turns out that the geometric change could become an important factor for the intrusion growth. Finally by replacing the plastic strain with creep strain the present model is easily extended to investigate the steady hysteresis loops for single crystal creep at elevated temperature. The results compare favorably with the available experimental data.
Correction and Control of Hyperammonemia in Acute Liver Failure: The Impact of Continuous Renal Replacement Timing, Intensity, and Duration.

OBJECTIVES Hyperammonemia is a key contributing factor for cerebral edema in acute liver failure. Continuous renal replacement therapy may help reduce ammonia levels. However, the optimal timing, mode, intensity, and duration of continuous renal replacement therapy in this setting are unknown. We aimed to study continuous renal replacement therapy use in acute liver failure patients and to assess its impact on hyperammonemia. DESIGN Retrospective observational study. SETTING ICU within a specialized liver transplant hospital. PATIENTS Fifty-four patients with acute liver failure. INTERVENTIONS Data were obtained from medical records and analyzed for patient characteristics, continuous renal replacement therapy use, ammonia dynamics, and outcomes. MAIN RESULTS Forty-five patients (83%) had high grade encephalopathy. Median time to continuous renal replacement therapy commencement was 4 hours (interquartile range, 2-4.5) with 35 (78%) treated with continuous venovenous hemodiafiltration and 10 (22%) with continuous venovenous hemofiltration. Median hourly effluent flow rate was 43 mL/kg (interquartile range, 37-62). The median ammonia concentration decreased every day during treatment from 151 µmol/L (interquartile range, 110-204) to 107 µmol/L (interquartile range, 84-133) on day 2, 75 µmol/L (interquartile range, 63-95) on day 3, and 52 µmol/L (interquartile range, 42-70) (p < 0.0001) on day 5. The number of patients with an ammonia level greater than 150 µmol/L decreased on the same days from 26, to nine, then two, and finally none. Reductions in ammonia levels correlated best with the cumulative duration of therapy hours (p = 0.03), rather than hourly treatment intensity. CONCLUSIONS Continuous renal replacement therapy is associated with reduced ammonia concentrations in acute liver failure patients. This effect is related to greater cumulative dose. These findings suggest that continuous renal replacement therapy initiated early and continued or longer may represent a useful approach to hyperammonemia control in acute liver failure patients.
Comparative effects of final canal irrigation with chitosan and EDTA

Abstract Chitosan is a natural, biocompatible chelating substance with potential for dental use. This study compared the effects of final canal irrigation with chitosan and EDTA on dentin microhardness, sealer dentin tubules penetration capacity, and push-out strength. Methodology: Fifty canine roots were distributed according to the final irrigation protocol (n=10): G1- 15% EDTA with conventional irrigation; G2- 15% EDTA with Endovac; G3- 0.2% chitosan with conventional irrigation; G4- 0.2% chitosan with Endovac; and G5- without irrigation. Specimens were obturated (AH Plus) and sectioned in 3 slices per root third. The first slice was used for microhardness and sealer penetration assessments under a laser confocal microscope. The second was utilized in a push-out strength test. The third slice was discarded. Data were analyzed using 2-way ANOVA and Tukey's post hoc test (α<0.05). Failure mode was determined at x40 magnification. Results: Microhardness reduction was more significant in groups G2 and G4 (p<0.05). Sealer penetration through dentin was significantly greater in group G2 (p<0.05). There was no significant difference between groups G1, G3, and G4 (p>0.05). In general, all experimental groups presented similar bond resistance (p>0.05) that significantly differed from the control (p<0.001). Mixed type failures were predominant. Conclusions: In general, 0.2% chitosan and 15% EDTA solutions act in a similar manner with regard to the variables studied. The use of Endovac potentiates the effect of these solutions.
Deep Green Diagnostics: Urban Green Space Analysis Using Deep Learning and Drone Images

Nowadays, more than half of the world’s population lives in urban areas, and this number continues increasing. Consequently, there are more and more scientific publications that analyze health problems of people associated with living in these highly urbanized locations. In particular, some of the recent work has focused on relating people’s health to the quality and quantity of urban green areas. In this context, and considering the huge amount of land area in large cities that must be supervised, our work seeks to develop a deep learning-based solution capable of determining the level of health of the land and to assess whether it is contaminated. The main purpose is to provide health institutions with software capable of creating updated maps that indicate where these phenomena are presented, as this information could be very useful to guide public health goals in large cities. Our software is released as open source code, and the data used for the experiments presented in this paper are also freely available.