Doganmoss5008

In sediment, the release of SDZ was significantly related to TN, TP, and organic matter. The risk quotient (RQ) results revealed that sulfamethoxazole (SMX), CIP, and ENR were at high risk to microorganisms in water; while, SMX and NOR were at high risk in sediments. The result from the estimated daily intakes (health risk quotient, HQ less then 1) suggested that the antibiotics might not pose a risk to human health by dietary exposure assessment; however, sediments may become an accumulation reservoir of antibiotics and cause secondary pollution, of which the local management should raise awareness.

Adiposity trajectories reflect dynamic process of growth and may predict later life health better than individual measures. Prenatal phthalate exposures may program later childhood adiposity, but findings from studies examining these associations are conflicting. We investigated associations between phthalate biomarker concentrations during pregnancy with child adiposity trajectories.

We followed 514 mother-child pairs from the Mexico City PROGRESS cohort from pregnancy through twelve years. We measured concentrations of nine phthalate biomarkers in 2nd and 3rd trimester maternal urine samples to create a pregnancy average using the geometric mean. We measured child BMI z-score, fat mass index (FMI), and waist-to-height ratio (WHtR) at three study visits between four and 12 years of age. We identified adiposity trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We estimated associations of phthalates biomarkers withiposity. The total phthalate mixture was not associated with early life child adiposity.

Prenatal concentrations of urinary DEHP metabolites, DiNP metabolites, and MCNP, a di-isodecyl phthalate metabolite, were associated with trajectories of child adiposity. The total phthalate mixture was not associated with early life child adiposity.In this study, we synthesized MnFe2O4 solid nanospheres (MSN) calcined at different temperatures (200-500 °C) and MSN-based materials mixed with carbon black, for their use as electrocatalysts in the oxygen reduction reaction (ORR) in alkaline medium (0.1 M KOH). It was demonstrated that the calcination temperature of MSN material determined its chemical surface composition and microstructure and it had an important effect on the electrocatalytic properties for ORR, which in turn was reflected in the performance of MSN/CB-based electrocatalysts. The study revealed that the presence of Mn species plays a key role in the ORR activity. Among tested, MSN200/CB and MSN350/CB exhibited the best electrochemical performances together with outstanding stability.Hereditary sensory neuropathy type 1 (HSAN1) is a rare axonopathy, characterized by a progressive loss of sensation (pain, temperature, and vibration), neuropathic pain and wound healing defects. HSAN1 is caused by several missense mutations in the SPTLC1 and SPTLC2 subunit of the enzyme serine-palmitoyltransferase (SPT) -the key enzyme for the synthesis of sphingolipids. The mutations change the substrate specificity of SPT, which then forms an atypical class of 1-deoxy-sphinglipids (1-deoxySL). Similarly, patients with type 2 diabetes (T2DM) also present with elevated 1-deoxySLs and a comparable clinical phenotype. The effect of 1-deoxySLs on neuronal cells was investigated in detail, but their impact on other cell types remains elusive. Here we investigated the consequences of externally added 1-deoxySLs on the migration of fibroblasts in a scratch assay as a simplified cellular wound-healing model. We showed that 1-deoxy-Sphinganine (1-deoxySA) inhibits the migration of NIH-3T3 fibroblasts in a dose- and time-dependent manner. This was not seen for a non-native, L-threo stereoisomer. Supplemented 1-deoxySA was metabolized to 1-deoxy-(dihydro)Ceramide and downstream to 1-deoxy-Sphingosine (1-deoxySO). Inhibiting downstream metabolism by blocking N-acylation rescued the migration phenotype. In contrast, adding 1-deoxySO had a lesser effect on cell migration but caused the massive formation of intracellular vacuoles. Further experiments showed, that the effect on cell migration was primarily mediated by 1-deoxy-dihydroceramides rather than by the free base or 1-deoxyceramides. Based on these findings, we suggest that limiting the N-acylation of 1-deoxySA could be a therapeutic approach to improve cell migration and wound healing in patients with HSAN1 and T2DM.Regulating dietary fat absorption may impact progression of nonalcoholic fatty liver disease (NAFLD). Here we asked if inducible inhibition of chylomicron assembly, as observed in intestine-specific microsomal triglyceride transfer protein knockout mice (Mttp-IKO), could retard NAFLD progression and/or reverse established fibrosis in two dietary models. Mttp-IKO mice fed a methionine/choline deficient (MCD) diet exhibited reduced hepatic triglycerides (TG), inflammation and fibrosis, associated with reduced oxidative stress and downstream activation of JNK and NFκB signaling pathways. However, when Mttpflox mice were fed a MCD for 5 weeks and then administered tamoxifen to induce Mttp-IKO, hepatic TG was reduced but inflammation and fibrosis were increased after 10 days reversal along with adaptive changes in hepatic lipogenic mRNAs. Extending the reversal time, following 5 weeks MCD feeding, to 30 days led to sustained reductions in hepatic TG but neither inflammation nor fibrosis were decreased and both intestinal permeability and hepatic lipogenesis were increased. In a second model, similar reductions in hepatic TG were observed when mice were fed a high fat/fructose/cholesterol diet for 10weeks, then switched to chow ± tamoxifen (HFFC→chow) or (HFFC→ Mttp-IKO chow), but again neither inflammation or fibrosis were affected. In conclusion, we found that blocking chylomicron assembly attenuates MCD-induced NAFLD progression by reducing steatosis, oxidative stress and inflammation. In contrast, blocking chylomicron assembly in the setting of established hepatic steatosis and fibrosis caused increased intestinal permeability and compensatory shifts in hepatic lipogenesis that mitigate resolution of inflammation and fibrogenic signaling despite 50-90 fold reductions in hepatic TG.Mesoionic compounds, 4-phenyl-5-(4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J X = OH; MI-D X = NO2), possess significant antitumor and cytotoxic effects on several cancer cells. In this work, we evaluated the cytotoxicity of MI-J and MI-D on human hepatocellular carcinoma (HepG2 cells) grown in either high glucose (HG) or galactose medium (GAL) to clarify whether the effects of mesoionics on mitochondrial bioenergetics are associated with their cytotoxicity in these cells. MI-J and MI-D (5-50 μM) decreased the viability of HepG2 cells in a dose- and time-dependent manner, as assessed by MTT, LDH release and dye with crystal violet assays. Both compounds at lower (5 μM) and intermediate (25 μM) concentrations were more toxic to cells grown in GAL medium. MI-J inhibited the basal state of respiration in HepG2 cells cultured in HG and GAL media; however, in GAL medium, this effect occurred at the lowest concentration (5 μM). A leak-state stimulus was observed only after incubation with MI-J (5 μM) for GAL medium. MI-D stimulated and inhibited the leak state in cells grown in HG medium at concentrations of 5 μM and 25 μM, respectively. In cells cultured in GAL medium, respiration was strongly inhibited by MI-D at the highest concentration (25 μM). In contrast, at 5 μM, the mesoionic inhibited the basal and uncoupled states at 30% and 50%, respectively. The inhibition of the basal state by MI-J and MI-D was consistent with the increase in lactate levels in both media, which was higher for the GAL medium. Both mesoionics slightly decreased pyruvate levels only in cells cultured in GAL medium. Additionally, MI-J (25 μM) reduced the ATP amount in cells cultured in both media, while MI-D (25 μM) promoted a reduction only in cells grown in GAL medium. Our results show that MI-J and MI-D depress mitochondrial respiration and consequently change metabolism and reduce ATP levels, effects associated with their toxicity in hepatocarcinoma cells.The potential usefulness of lopinavir-ritonavir on Covid 19 infection during the first wave of contamination in France had boosted Kaletra® syrup prescription to the point of causing its national shortage. In the intensive care units of Parisian hospitals in charge of patients with life-threatening viral contamination, caregivers had to resort to lopinavir-ritonavir-based tablets, crushing them and then dispersing the powder in milk to facilitate administration by nasogastric tube. The difficulties and poor control of this degraded mode, which does not always ensure control of the amount of the drug in the prepared dose and may induce insufficient antiviral exposure, led us to develop in a very short time, while ensuring quality control proportional to the risk, a liquid form as an alternative to Kaletra® oral solution shortage. For this purpose, we describe this compounding formulation and its preparation process, while justifying the quality control strategy adapted to the risk as well as its chemical and physical stability. Based on the chemical and physical studies, the preparation was showed to be stable during at least 2 months between +2°C and +8°C and 1 week at room temperature. This has resulted in the design of kits that include multi-dose packaging and a measuring device and contain the appropriate quantities of drugs to ensure at least one week's treatment for each patient, during which time the kit in use can be stored at room temperature. The intensive care team used this treatment under conditions that they considered well adapted until the imported specialty became available.Osteoarthritis (OA) patients undergo cartilage degradation and experience painful joint swelling. OA symptoms are caused by inflammatory molecules and the upregulation of catabolic genes leading to the breakdown of cartilage extracellular matrix (ECM). Here, we investigate the effects of gallic acid (GA) and mechanical stretching on the expression of anabolic and catabolic genes and restoring ECM production by osteoarthritic human articular chondrocytes (hAChs) cultured in monolayers. hAChs were seeded onto conventional plates or silicone chambers with or without 100 μM GA. A 5% cyclic tensile strain (CTS) was applied to the silicone chambers and the deposition of collagen and glycosaminoglycan, and gene expressions of collagen types II (COL2A1), XI (COL11A2), I (COL1A1), and X (COL10A1), and matrix metalloproteinases (MMP-1 and MMP-13) as inflammation markers, were quantified. CTS and GA acted synergistically to promote the deposition of collagen and glycosaminoglycan in the ECM by 14- and 7-fold, respectively. Furthermore, the synergistic stimuli selectively upregulated the expression of cartilage-specific proteins, COL11A2 by 7-fold, and COL2A1 by 47-fold, and, in contrast, downregulated the expression of MMP-1 by 2.5-fold and MMP-13 by 125-fold. GA supplementation with CTS is a promising approach for restoring osteoarthritic hAChs ECM production ability making them suitable for complex tissue engineering applications.Some discoveries resulted from 2-dimensional (2D) cultured cardiac cells have been disqualified in animal testing and later clinical trials. Extracellular matrix (ECM) plays a vital role in cardiac homeostasis, cardiac ECM (cECM)-based 3D cell cultures can mimics the physiological and pathological conditions in vivo closely, it is hopeful of addressing this challenge. Construction of cECM-based 3-dimensional (3D) hydrogel (cECM3DH) and its effects on cell behaviors were studied here. The results indicated that cellular compartments could be efficiently removed from heart tissue via sodium dodecyl sulfonate (SDS)- and Triton X-100-mediated decellularization, remaining the natural fibrous network structure and major proteins. 3D hydrogel consisted of 1 × 107 cells/mL cells and 75% cECM could promote the proliferation and anti-apoptosis ability of human embryonic kidney (HEK)-293T cells. 0.25% trypsin or 0.20% collagenase was suitable to retrieve these cells from 3D hydrogel for further researches. Compared with 2D culture system, cECM3DH could significantly increase the proportion of GATA 4+ cardiomyocytes (CMs) derived from heart tissue of neonatal mouse or induced differentiation of embryonic stem cells (ESCs) (P less then 0.05) The expression levels of mature genes including cTnT, JCN, CaV1.2, MYL2, CASQ2, NCX1, and Cx43 of these CMs in adult pig cECM-based 3D hydrogel (APcECM3DH) were significantly higher than that in 2D culture system and in newborn piglet cECM-based 3D hydrogel (NPcECM3DH), respectively (P less then 0.05). Therefore, cECM3DH supports the generation of primary CMs and ESC-derived CMs, APcECM3DH was more conducive to promoting CM maturation, which contributes to building 3D model for pathogenesis exploration, drug screening, and regenerative medicine of heart diseases.We explore the role of miR-125b in septic cardiomyopathy, focusing on miR-125b/STAT3/HMGB1 axis. CLP mouse model and LPS-stimulated primary rat cardiomyocytes (CMs) and H9C2 cell were used as in vivo and in vitro models of septic cardiomyopathy, respectively. qRT-PCR and western blot were performed to measure expression levels of miR-125b, STAT3, HMGB1, and autophagy-related proteins. MTT assay was employed to examine LPS toxicity. Dual luciferase activity assay and CHIP were performed to validate interactions of miR-125b/STAT3 and STAT3/HMGB1 promoter. Immunostaining was used to assess the level of autophagic flux. ROS level was measured by fluorescence assay. Heart functions were examined via intracoronary Doppler ultrasound. miR-125b was diminished while STAT3 and HMGB1 were elevated in the heart tissue following CLP surgery and in LPS-treated H9C2 cells. LPS treatment up-regulated ROS generation and suppressed autophagic flux. Overexpression of miR-125b mimics or knockdown of STAT3 or HMGB1 alleviated LPS-induced hindrance of autophagic flux and ROS production. miR-125b directly targeted STAT3 mRNA and STAT3 bound with HMGB1 promoter. Overexpression of miR-125b mitigated myocardial dysfunction induced by CLP in vivo. Hyperactivation of STAT3/HMGB1 caused by reduced miR-125b contributes to ROS generation and the hindrance of autophagic flux during septic cardiomyopathy, leading to myocardial dysfunction.Manual urine sediment analysis of a sample obtained from a 5 year old child by our clinical diagnostics laboratory revealed abundant "daisy-like" crystals, which have been first described in 2004 and found to be extremely rare in a follow-up publication by the same research group. To date only 12 samples have been described in the literature containing such crystals. Upon further investigation on how the sample was obtained, we were able to reproduce the process without any biological specimen involved. We show that these crystals are in fact contaminants from the sample collection recipient itself, which was a glass recipient sterilized by the patient's family the night before sample collection, by boiling water with high calcium and magnesium content (hard water), and letting the recipient cool overnight with the water in it. The obtained abundant "daisy-like" crystals readily dissolve in acidic environment, and are composed most likely of mostly calcium carbonate. Sampling artifacts are therefore a possible explanation for at least some of the previously described "daisy-like" urinary crystals, as the formation of such crystals does not need to involve any biomolecules, only hard water and appropriate crystallization conditions for the limescale in it.Herein, we investigate whether alterations in the microtubule cytoskeleton affect the ability of endothelial cells (ECs) to sprout and form branching networks of tubes. Using defined bioassays of human EC tubulogenesis, where both sprouting behavior and lumen formation can be rigorously evaluated, we demonstrate that addition of the microtubule-stabilizing drugs, paclitaxel, docetaxel, ixabepilone, and epothilone B, completely interferes with EC tip cells and sprouting behavior, while allowing for EC lumen formation. In bioassays mimicking vasculogenesis using single or aggregated ECs, these drugs induce ring-like lumens from single cells or cyst-like spherical lumens from multicellular aggregates with no evidence of EC sprouting behavior. Remarkably, treatment of these cultures with a low dose of the microtubule-destabilizing drug, vinblastine, leads to an identical result, with complete blockade of EC sprouting, but allowing for EC lumen formation. Supporting our findings, administration of paclitaxel in vivo markedly interferes with angiogenic sprouting behavior in developing mouse retina. These findings reveal novel biological activities for pharmacologic agents that are widely utilized in multidrug chemotherapeutic regimens for the treatment of human malignant cancers. Overall, this work demonstrates that manipulation of microtubule stability selectively interferes with the ability of ECs to sprout, a necessary step to initiate and form branched capillary tube networks.Alzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Recently, studies show that H3R are highly expressed not only in neurons but also in microglia and astrocytes. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation in glial cells and neuroprotection on APPswe, PSEN1dE9 (APP/PS1 Tg) mice remain unclear. In this study, we found that inhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated P65 nuclear factor kappa B (p-P65 NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of amyloid-β (Aβ) and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. Taken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aβ clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.A recent advancement in the field of neuromodulation is to adapt stimulation parameters according to pre-specified biomarkers tracked in real-time. These markers comprise short and transient signal features, such as bursts of elevated band power. To capture these features, instantaneous measures of phase and/or amplitude are employed, which inform stimulation adjustment with high temporal specificity. For adaptive neuromodulation it is therefore necessary to precisely estimate a signal's phase and amplitude with minimum delay and in a causal way, i.e. without depending on future parts of the signal. Here we demonstrate a method that utilizes oscillation theory to estimate phase and amplitude in real-time and compare it to a recently proposed causal modification of the Hilbert transform. By simulating real-time processing of human LFP data, we show that our approach almost perfectly tracks offline phase and amplitude with minimum delay and is computationally highly efficient.Ischemic stroke is one of the most lethal and severely disabling diseases that seriously affects human health and quality of life. The maintenance of self-renewal and differentiation of neural stem cells are closely related to metabolism. This study aimed to investigate whether hypoxic postconditioning (HPC) could promote neurogenesis after ischemic stroke, and to investigate the role of neuronal stem cell metabolism in HPC-induced neuroprotection. Male C57BL/6 mice were subjected to transient middle cerebral artery occlusion (MCAO), and HPC was performed for 3 h per day. Immunofluorescence staining was used to assess neurogenesis. The cell line NE-4C was used to elucidate the proliferation of neuronal stem cells in 21% O2 or 8% O2. HPC promoted the recovery of neurological function in mice on day 14. HPC promoted neuronal precursor proliferation in the subventricular zone (SVZ) on day 7 and enhanced neuronal precursor migration in the basal ganglia and cortex on day 14. Fatty acid oxidation (FAO) and glycolysis of neural stem cells in the SVZ changed after MCAO with or without HPC. HPC promoted the proliferation of NE-4C stem cells, decreased FAO and increased glycolysis. All these beneficial effects of HPC were ablated by the application of an FAO activator or a glycolysis inhibitor. In conclusion, cerebral ischemia modulated the FAO and glycolysis of neural stem cells. HPC promoted the proliferation and migration of neural stem cells after MCAO, and these effects may be related to the regulation of metabolism, including FAO and glycolysis.Trypanosoma rangeli is a non-virulent hemoflagellate parasite infecting humans, wild and domestic mammals in Central and Latin America. The share of genotypic, phenotypic, and biological similarities with the virulent, human-infective T. cruzi and T. brucei, allows comparative studies on mechanisms of pathogenesis. In this study, investigation of the T. rangeli Arginine Kinase (TrAK) revealed two highly similar copies of the AK gene in this taxon, and a distinct expression profile and activity between replicative and infective forms. Although TrAK expression seems stable during epimastigotes growth, the enzymatic activity increases during the exponential growth phase and decreases from the stationary phase onwards. No differences were observed in activity or expression levels of TrAK during in vitro differentiation from epimastigotes to infective forms, and no detectable AK expression was observed for blood trypomastigotes. Overexpression of TrAK by T. rangeli showed no effects on the in vitro growth pattern, differentiation to infective forms, or infectivity to mice and triatomines. Although differences in TrAK expression and activity were observed among T. rangeli strains from distinct genetic lineages, our results indicate an up-regulation during parasite replication and putative post-translational myristoylation of this enzyme. We conclude that up-regulation of TrAK activity in epimastigotes appears to improve proliferation fitness, while reduced TrAK expression in blood trypomastigotes may be related to short-term and subpatent parasitemia in mammalian hosts.

The identification of C-shaped root-canal anatomy on radiographic images affects clinical decision-making and treatment. Aims of this study were to develop a Deep Learning (DL) model to classify C-shaped canal anatomy in mandibular second molars from Cone Beam CT (CBCT) volumes and to compare the performance of three different architectures.

U-Net, Residual U-Net, and Xception U-Net architectures were used for image segmentation and classification of C-shape anatomies. Model training and validation was performed on 100 of a total of 135 available limited field of view CBCTs containing mandibular molars with C-shape anatomy. 35 CBCTs were used for testing. Voxel-matching accuracy of the automated labeling of the C-Shape anatomy was assessed with the DICE index. Mean sensitivity of predicting the correct C-shape subcategory was calculated based on detection accuracy. One-way ANOVA and Post-Hoc Tukey HSD tests were used for statistical evaluation.

Mean DICE coefficients were 0.768±0.0349 for Xception U-Net, 0.736±0.0297 for Residual U-Net, and 0.660±0.0354 for U-Net on the test dataset. The performance of the three models was significantly different overall (ANOVA;P=.000779). Both Xception U-Net (Q=7.23;P=0.00070) and Residual U-Net (Q=5.09;P=0.00951) performed significantly better than U-Net (Post-Hoc Tukey HSD). Mean sensitivity values were 0.786±0.0378 for Xception U-Net, 0.746±0.0391 for Residual U-Net and 0.720±0.0495 for U-Net. Mean Positive Predictive Values (PPV) were 77.6%±0.1998 for U-Net, 78.2%±0.0.1971 for Residual U-Net, and 80.0%±0.1098 for Xception U-Net. Addition of contrast limited adaptive histogram equalization (CLAHE) had improved overall architecture efficacy by mean 4.6% (P<0.0001).

DL may aid in the detection and classification of C-shaped canal anatomy.

DL may aid in the detection and classification of C-shaped canal anatomy.

This study aimed to assess the pulpal and restorative outcome of full pulpotomy in symptomatic mature permanent teeth with carious pulp exposure over 4 years.

Under local anesthesia full pulpotomy was performed using aseptic technique and a stain-proof calcium silicate-based material (NeoMTA Plus, Avalon Biomed Inc. Florida, USA). Pain level was scored preoperatively and 1week post treatment. Clinical and radiographic evaluation was performed at 6 months, 1, 2 and 4 years. Kaplan-Meier Survival Analysis and Cox proportional hazards regression were used to analyze the data. Failed cases were classified as endodontic or restorative failure.

Full pulpotomy completed in 109 teeth in 90 patients with age range of 14-60 years (mean 25 years). Study sample available for follow up was 100 teeth in 86 patients with a recall rate above 90%. Preoperative pulp diagnosis was reversible pulpitis in 39 teeth and irreversible pulpitis in 61teeth. The cumulative survival rates of pulpotomy were generally high; 98%, 97.4%, 93%, 83.8% at 6 months, 1, 2 and 4 years, respectively. The overall mean survival time of pulpotomy was 3.89 years (95% CI 3.84-3.95). The mean survival time was significantly higher for patients aged ≤25 years. However, in the multivariate analysis the only significant predictor of pulpotomy failure was sever preoperative pain. Over the 4 years 23 cases failed; only10/23 failures were classified as endodontic failure and the success of pulpotomy can be assumed to be 90%.

Full pulpotomy in cariously exposed pulps of mature permanent teeth sustained a high success rate over 4 years. Coronal seal is crucial for long term survival.

Full pulpotomy in cariously exposed pulps of mature permanent teeth sustained a high success rate over 4 years. Coronal seal is crucial for long term survival.

To compare clinical and hemodynamic in-hospital outcomes of patients undergoing sutureless versus rapid deployment aortic valve replacement (SURD-AVR) in the large population of the Sutureless and Rapid Deployment International Registry (SURD-IR).

We examined 4695 patients who underwent isolated or combined SURD-AVR. The "sutureless" Perceval valve was used in 3133 patients and the "rapid deployment" Intuity in 1562. Potential confounding factors were addressed by the use of propensity score matching. After matching, 2 well-balanced cohorts of 823 pairs (isolated SURD-AVR) and 467 pairs (combined SURD-AVR) were created.

Patients who received Perceval and Intuity valves showed similar in-hospital mortality and rate of major postoperative complications. Perceval was associated shorter cross clamp and cardiopulmonary bypass time. In the isolated SURD-AVR group, patients receiving Perceval were more likely to undergo anterior right thoracotomy incision. Postoperative transvalvular gradients were significantly lower for the Intuity valve compared to those of the Perceval valve, either in isolated and combined SURD-AVR. The Intuity valve was associated with a lower rate of postoperative mild aortic regurgitation.

Our results confirm the safety and efficacy of SURD-AVR regardless of the valve type. The Perceval valve was associated with reduced operative times and increased anterior right thoracotomy incision. The Intuity valve showed superior hemodynamic outcomes and a lower incidence of postoperative mild aortic regurgitation.

Our results confirm the safety and efficacy of SURD-AVR regardless of the valve type. The Perceval valve was associated with reduced operative times and increased anterior right thoracotomy incision. The Intuity valve showed superior hemodynamic outcomes and a lower incidence of postoperative mild aortic regurgitation.

The efficacy of segmentectomy for inner small-sized non-small-cell lung cancer (NSCLC) remains unknown. We aimed to elucidate whether segmentectomy for inner small-sized NSCLC, defined using novel three-dimensional measuring method, yields feasible oncological outcomes compared to segmentectomy for outer lesions.

We retrospectively analyzed patients with small-sized (<2cm) cN0 NSCLC who underwent segmentectomy between January 2007 and December 2020. Tumor centrality ratio, which was measured by using three dimensional reconstruction software, was evaluated, with the location of tumor origin confirmed pathologically. Cases with a ratio below and above 2/3 were allocated to the 'Inner group' and 'Outer group', respectively. Oncological outcomes were compared between the two groups.

Our cohort was divided into the 'Inner group' (n=75) and 'Outer group' (n=127). The proximal distance from a tumor exceeded 20 mm in all cases. Tumor centrality ratio was associated with the pathological origin of a tumor. The rate of unforeseen positive lymph node metastasis was significantly higher in the 'Inner group' (p=0.04). There were no significant differences in the 5-year recurrence free survival (RFS; 91% versus 87%, p=0.67). Univariate analysis identified age, consolidation/tumor ratio, the presence of ground-glass-opacity (GGO) and lymphovascular invasion, but not tumor centrality, as significant prognostic factors for RFS. In the multivariate analysis, the presence of GGO and lymphovascular invasion remained significant.

Regarding oncological outcomes, segmentectomy with a safety proximal distance could be feasible, even for inner small-sized NSCLC. Tumor invasiveness, not tumor centrality, may influence tumor recurrence. (242 words).

Regarding oncological outcomes, segmentectomy with a safety proximal distance could be feasible, even for inner small-sized NSCLC. Tumor invasiveness, not tumor centrality, may influence tumor recurrence. (242 words).

Patients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common amongst children is post-transplant lymphoproliferative disorder (PTLD), occurring in 5-10% of patients. We utilized a national database to examine incidence and risk factors for post-transplant malignancy.

The United Network for Organ Sharing (UNOS) database was queried for pediatric (<18 years) heart transplant recipients from 10/1987-10/2019. Kaplan-Meier analysis was performed to assess freedom from malignancy post-transplant. Cox regression was performed to generate hazard ratios (HR [95% CI]) for risk of malignancy development.

Of 8,581 pediatric heart transplant recipients, 8.1% developed malignancy over median follow-up time of 6.3 years, with PTLD compromising the majority (86.4%) of diagnosed cancers. The incidence of PTLD development was 1.3% and 4.5% at one and five years. Older age at the time of transplant was protective against the developts, does not seem to increase post-transplant malignancy, nor does the most commonly used calcineurin inhibitor tacrolimus.

Meta-analytic comparison of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) versus percutaneous gallbladder drainage (PT-GBD) for acute cholecystitis (AC) brings the risk of spurious results if too few studies are included. Trial sequential analysis (TSA) can overcome this, providing information about its credibility.

Comparative studies between EUS-GBD, using lumen-apposing metal stents (LAMSs), and PT-GBD for AC until July 2021 were used for conventional meta-analysis and TSA, which allowed the use of monitoring boundaries and the estimation of the required information size (RIS) needed to prove credibility.

Four studies accrued 535 patients. Technical success was in favor of PT-GBD (relative risk [RR] 0.967; p=0.036) but TSA estimated that 1663 participants would be needed to avoid type 1 error (false positive). Clinical success was similar (RR, 0.965; p=0.146), and TSA supported the absence of any demonstrable superiority of one therapy, rather than a type 2 error (false negative). EUS-Gs additional studies.

Endoscopist recommendations around repeating colonoscopy after inadequate bowel cleanliness have not been fully described. Our aim was to evaluate the timing of recommendations for repeat colonoscopy after inadequate bowel preparation using a large, national colonoscopy registry.

We performed a cross-sectional analysis of all outpatient screening and surveillance colonoscopies among adults age 50 to 75 reported in the GI Quality Improvement Consortium (GIQuIC) from 2011 to 2018. The primary outcome was a recommendation to repeat colonoscopy within 1 year. Secondary outcomes included recommendations based on indication of colonoscopy and colonoscopy findings, and predictors of a recommendation to follow-up within 1 year.

There were 260,314 colonoscopies with inadequate bowel preparation performed at 672 different sites by 4,001 endoscopists. Of these, 31.9% contained a recommendation for follow-up within 1 year. This did not differ meaningfully by examination indication. The severity of colonoscopy findings influenced the recommendations for follow-up (within 1 year in 84.0% of cases with adenocarcinoma, 51.8% with any advanced lesion, and 23.2% with 1-2 small adenomas). Younger age, more severe pathology, location in the Northeast, and performance by an endoscopist with an adenoma detection rate ≥25% were associated with recommendations for follow-up within 1 year.

A minority of colonoscopies with inadequate bowel preparation are recommended to be repeated within 1 year, which may have implications for potential missed lesions. Further understanding of reasons driving recommendations is an important next step to improving guideline-concordant colonoscopy practice.

A minority of colonoscopies with inadequate bowel preparation are recommended to be repeated within 1 year, which may have implications for potential missed lesions. Further understanding of reasons driving recommendations is an important next step to improving guideline-concordant colonoscopy practice.

Mental health conditions during delivery hospitalizations are not well characterized.

This study aimed to characterize the prevalence of maternal mental health condition diagnoses and associated risk during delivery hospitalizations in the United States.

The 2000 to 2018 National Inpatient Sample was used for this repeated cross-sectional analysis. Delivery hospitalizations of women aged 15 to 54 years with and without mental health condition diagnoses, including depressive disorder, anxiety disorder, bipolar spectrum disorder, and schizophrenia spectrum disorder, were identified. Temporal trends in mental health condition diagnoses during delivery hospitalizations were determined using the National Cancer Institute's Joinpoint Regression Program to estimate the average annual percent change with 95% confidence intervals. The trends in chronic conditions associated with mental health condition diagnoses, including asthma, pregestational diabetes mellitus, chronic hypertension, obesity, and substance use condition diagnoses increased significantly throughout the study period. Mental health condition diagnoses were associated with other underlying chronic health conditions and a modestly increased risk of a range of adverse outcomes. The findings suggested that mental health conditions are an important risk factor in adverse maternal outcomes.

Opportunistic bilateral salpingo-oophorectomy (BSO) is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with BSO in this population remains unclear, and must be weighed against potential risks of ovarian hormone deficiency.

To quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with BSO at the time of benign hysterectomy.

We performed a population-based cohort study of all adult women (>20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, prior breast/gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment weighted Fine & Gray subdistribution hazard models were used to quantify the effect of BSO on ovarian cancer incidence and death, while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbi hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of BSO in order to inform practice guidelines, patient decision-making, and surgical management.

BSO results in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of BSO in order to inform practice guidelines, patient decision-making, and surgical management.Food selectivity has been shown to be more persistent and severe in children with Tourette syndrome (TS) compared to their typically developing peers. The current study aimed to examine differences in food selectivity, food neophobia and Avoidant Restrictive Food Intake Disorder (ARFID)-associated behaviours, between adults with and without TS. Fifty-three adults diagnosed with TS were compared to 53 neurotypical adults and completed the following measures online Adult Eating Behaviour Questionnaire (AEBQ), Nine-Item Avoidant/Restrictive Food Intake disorder screen (NIAS), Food Neophobia Scale (FNS) and the Sensory Perception Quotient (SPQ). Higher levels of food avoidant behaviours, in terms of food fussiness, food neophobia and ARFID-associated behaviours, were identified in adults with TS compared to adults without TS. While heightened sensory sensitivity failed to predict food fussiness, greater sensitivity to taste was found to be predictive of food neophobia in TS. These are the first findings to suggest that food avoidant behaviours are more prevalent for adults with TS and signal a need to address health implications.Bromodomains are a group of structurally diverse proteins characterized as readers of post-translational modifications. They bear unique structural topology and are known to have diverse cellular functions. As epigenetic readers of histone acetylation, bromodomains appear to have both physiological and pathological implications. Among the various types of bromodomain-containing proteins, BRD2 and BRD4 proteins are expressed ubiquitously and act as critical regulators of the cell cycle in normal mammalian cells. Therefore, they are increasingly involved in the process of oncogenesis. Bromodomains are the emerging novel epigenetic targets for the treatment of cancer. Various small molecules are proposed to target the bromodomain proteins as the readers of acetyl-lysine residues. In recent years, inhibiting the interaction of acetyl-lysine residues and bromodomain proteins on chromatin has served as an interesting target to regulate the expression of various pathological genes, including BCL-2, MYC, and NF-κB. The review summarizes bromodomains as potential targets in cancer and various bromodomain inhibitors in the early stages of the clinical trial.

Little is known about the causality and pathological mechanism underlying the association between old age and myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the association between old age and myocardial injury in STEMI patients undergoing primary percutaneous coronary intervention (PCI) using cardiovascular magnetic resonance imaging (CMR).

A total of 279 patients with STEMI who underwent primary PCI and CMR were enrolled. Of these, 52 patients were over the age of 70 years (18.6%, Age ≥70 group) and 227 patients were under the age of 70 years (81.4%, Age <70 group) at STEMI occurrence. We compared myocardial infarct size on CMR according to age at STEMI occurrence and performed inverse probability of treatment weighting.

On CMR analysis, myocardial infarct size on CMR tended to be greater in the Age ≥70 group than in the Age <70 group (21.2 ± 10.2% versus 19.5 ± 11.1%; p = 0.072). After performing inverse probability of treatment weighting adjustment, myocardial infarct size was significantly greater in the Age ≥70 group compared with the Age <70 group (22.6 ± 10.4% versus 19.6 ± 11.1%; p = 0.001). Subgroup analysis of patients older than 70 years revealed no significant difference in myocardial infarct size according to sex (20.1 ± 11.5% in females versus 20.4 ± 9.9% in males; p = 0.901).

Despite appropriate coronary revascularization, old age was associated with greater extent of myocardial injury in STEMI patients.

Despite appropriate coronary revascularization, old age was associated with greater extent of myocardial injury in STEMI patients.

Homeless and marginally housed populations experience a higher prevalence of visual impairment relative to the general population. The aim of this pilot study is to present a novel model for conducting ocular screening clinics for homeless individuals during a pandemic and to describe the status of ocular health in this population during this time.

In this cross-sectional study, 3 outdoor tent-based ocular screening clinics were held in a park in Toronto. Most participants were recruited from local shelters, but additional spots were allocated for homeless individuals on a drop-in basis. Prior to enrolment, each participant underwent COVID-19 screening via a questionnaire and temperature measurement. Those who screened negative received a comprehensive eye examination, including vision testing, dilated fundus examination, and autorefraction.

Eleven individuals completed all assessments. The mean age of participants was 54.5 years, and 11 of the participants were male. Visual impairment was found in 5 individuals. Refractive error via pinhole testing was found in 1 patient. Ocular pathology in this sample was found in 4 participants. Two patients required a referral to an ophthalmologist. From a psychosocial perspective, 4 participants reported significant difficulties.

This novel tent-based ocular screening program provides a viable option for screening in a pandemic.

This novel tent-based ocular screening program provides a viable option for screening in a pandemic.Influenza increases morbidity and mortality in systemic lupus erythematosus and lupus nephritis but is preventable through vaccination. This systematic review of PubMed, Embase, CENTRAL, WHO Clinical Trials and ClinicalTrials.gov publications until August 2021 identified 45 reports (16596 patients), including 8.5% with renal involvement or lupus nephritis 9 studies (10446 patients) on clinical effectiveness, 20 studies (1327 patients) on vaccine efficacy, 22 studies (1116 patients) on vaccine safety, 14 studies (4619 patients) on utilization rates and 5 studies (3220 patients) on barriers. Pooled seroconversion rates ranged 46-56% while seroprotection rates ranged 68-73% and was significantly associated with age and disease duration. Influenza infection was lower in vaccinated systemic lupus erythematosus patients compared to unvaccinated patients. Disease activity scores did not change significantly after vaccination and reported flares were mild to moderate. Pooled current vaccination rate was 40.0% (95% CI 33.7-46.5%) with significant heterogeneity and associated with the gross domestic product (p=0.002) and disease duration (p=0.001). Barriers to vaccination were the lack of doctor recommendation (57.4%) and concerns over the safety or efficacy of the vaccine (12.7%).

Knowledge about COVID-19 in pregnancy is limited, and evidence on the impact of the infection during pregnancy and postpartum is still emerging.

To analyze maternal morbidity and mortality due to severe acute respiratory infections (SARI), including COVID-19, in Brazil.

National surveillance data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) was used to describe currently and recently pregnant women aged 10-49 years hospitalized for SARI from January through November, 2020. SARI cases were grouped into COVID-19; influenza or other detected agent SARI; and SARI of unknown etiology. Characteristics, symptoms and outcomes were presented by SARI type and region. Binomial proportion and 95% confidence intervals (95% CI) for outcomes were obtained using the Clopper-Pearson method.

Of 945,460 SARI cases in the SIVEP-Gripe, we selected 11,074 women aged 10-49 who were pregnant (7964) or recently pregnant (3110). COVID-19 was confirmed in 49.4% cases; 1.7% had influenza or another etiological agent; and 48.9% had SARI of unknown etiology. The pardo race/ethnic group accounted for 50% of SARI cases. Hypertension/Other cardiovascular diseases, chronic respiratory diseases, diabetes, and obesity were the most common comorbidities. A total of 362 women with COVID-19 (6.6%; 95%CI 6.0-7.3) died. Mortality was 4.7% (2.2-8.8) among influenza patients, and 3.3% (2.9-3.8) among those with SARI of unknown etiology. The South-East, Northeast and North regions recorded the highest frequencies of mortality among COVID-19 patients.

Mortality among pregnant and recently pregnant women with SARIs was elevated among those with COVID-19, particularly in regions where maternal mortality is already high.

Mortality among pregnant and recently pregnant women with SARIs was elevated among those with COVID-19, particularly in regions where maternal mortality is already high.

The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase.

A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution.

All patients received a 6mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died.

Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them.

Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020.

A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas.

ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Black men are more likely to die of prostate cancer (PCa) than White men. Whether this difference is driven by biological versus sociodemographic and access to care differences is actively investigated. However, studies that have highlighted racial disparities in PCa outcomes have been poorly represented by elderly men, a notoriously undertreated group. Herein, we evaluated use of curative treatment between Black and White elderly men with aggressive PCa in a large US database.

Men ≥80years diagnosed with National Comprehensive Cancer Network-defined high risk PCa between 2004 and 2016 were analyzed from the National Cancer Database. Multivariable logistic regression was used to model the effect of race and sociodemographic factors on receipt of definitive therapy (surgery or radiation +/- androgen deprivation therapy [ADT]) versus non-definitive therapy (ADT alone or observation) in inverse probability weighted groups matched for stage, prostate-specific antigen, and Gleason score.

Between 2004 and 2016, utilization of definitive therapy with either surgery or radiation therapy increased in both White and Black men in the United States. However, we found that Black men compared with White men were significantly less likely to receive definitive therapy (OR 0.71, 95% CI 0.64-0.79, p<.001). Using multivariable modeling, effect size diminished after adjusting for sociodemographic variables. Notably, there is evidence of the racial disparity narrowing over time.

These findings highlight striking but improving racial disparities in elderly men with high risk PCa in the US, an overall undertreated population.

These findings highlight striking but improving racial disparities in elderly men with high risk PCa in the US, an overall undertreated population.

In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response.

We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression.

780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies.