Maynardcrews2499
The procholecystokinin (proCCK) gene encodes a secreted peptide known to regulate the digestive, endocrine, and nervous systems. Though recently proposed as a biomarker for heart dysfunction, its physiological role in both the embryonic and adult heart is poorly understood, and there are no reports of tissue-specific regulators of cholecystokinin signaling in the heart or other tissues. In the present study, mRNA of proCCK was observed in cardiac tissues during mouse embryonic development, establishing proCCK as an early marker of differentiated cardiomyocytes which is later restricted to anatomical subdomains of the neonatal heart. Three-dimensional analysis of the expression of proCCK and CCKAR/CCKBR receptors was performed using in situ hybridization and optical projection tomography, illustrating chamber-specific expression patterns in the postnatal heart. Transcription factor motif analyses indicated developmental cardiac transcription factors TBX5 and MEF2C as upstream regulators of proCCK, and this regulatory activity was confirmed in reporter gene assays. proCCK mRNA levels were also measured in the infarcted heart and in response to cyclic mechanical stretch and endothelin-1, indicating dynamic transcriptional regulation which might be leveraged for improved biomarker development. Functional analyses of exogenous cholecystokinin octapeptide (CCK-8) administration were performed in differentiating mouse embryonic stem cells (mESCs), and the results suggest that CCK-8 does not act as a differentiation modulator of cardiomyocyte subtypes. O6-Benzylguanine inhibitor Collectively, these findings indicate that proCCK is regulated at the transcriptional level by TBX5-MEF2 and neurohormonal signaling, informing use of proCCK as a biomarker and future strategies for upstream manipulation of cholecystokinin signaling in the heart and other tissues.
Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival.
This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan-Meier method was used to measure survival and predictors of survival were identified with the Cox regression model.
A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/-9.9) and the median MELD was 13.3 (IQR 9.5-16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%.
TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.
TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.
To quantify the density of the macular microvasculature and the area of the foveal avascular zone (FAZ) in patients recovered from coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography (OCTA) analysis.
In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included in this study. All included subjects exhibited a reverse transcription-polymerase chain reaction-confirmed diagnosis of COVID-19. Spectral domain macular OCTA was performed at least 2 weeks after recovery from systemic COVID-19. Vessel density (VD) of the superficial (SCP) and deep retinal capillary plexus (DCP) and the area of the FAZ were measured in COVID-19 recovered patients versus age-matched normal controls.
Thirty-one recovered COVID-19 patients and 23 healthy normal controls were studied. Mean quality scan index was 7.64 ± 0.66 in the COVID cases and 8.34 ± 0.71 in the normal controls (p = 0.001). Mean SCP VD and DCP VD of the COVID cohort were significantly lower than the SCP VD and DCP VD of the control group in the foveal and parafoveal regions. FAZ area was greater in the COVID cohort, but this difference was not statistically significant. In addition, in the COVID cohort, VD of the SCP was lower in patients with a history of COVID-19 hospitalization versus those without such a history, but this did not reach statistical significance.
Patients recovered from COVID-19 displayed alterations in the retinal microvasculature, including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications.
Patients recovered from COVID-19 displayed alterations in the retinal microvasculature, including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications.
To investigate if an aminomethacrylate copolymer (AMC) could potentiate the anti-erosive effect of solutions containing sodium fluoride -F (225 ppm F
) and sodium fluoride associated to stannous chloride -FS (800 ppm Sn
).
The experimental solutions (F, FS, AMC, AMC + F, AMC + FS, and deionized water-DW as negative control) were tested in the presence of acquired pellicle. Polished bovine enamel specimens (n = 13/group) were submitted to an erosion-rehardening cycle (2 h immersion in human saliva, 5 min in 0.3 % citric acid, 1 h in human saliva, 4×/day, 5 days). Treatment with the solutions was performed for 2 min, 2×/day. The rehardening (%Re) and protective (%Prot) potential of the solutions were assessed in the beginning of the experiment, and the surface loss (SL) by contact profilometry after 5 days. Additional bovine specimens (n = 5/group) were prepared to evaluate the contact angle on the treated enamel surface. The zeta potential of the dispersed hydroxyapatite (HA) crystals after the treatment with the solutions was also measured (n = 3/group). Data were statistically analyzed (α = 0.05).
The association with AMC improved the %Re and the %Prot for W and F, but not for FS. The results of SL were AMC + F = AMC + FS < AMC < FS < F < DW. The presence of AMC significantly reduced the contact angle on enamel surfaces. The HA presented a strong negative surface charge after the treatment with DW, F and FS, whereas after the treatment with the solutions containing AMC it became positive.
AMC has potential to enhance the anti-erosive effect of fluoride solutions.
The aminomethacrylate copolymer (AMC) may be a promising agent to be added to oral care products for the prevention of erosive tooth wear.
The aminomethacrylate copolymer (AMC) may be a promising agent to be added to oral care products for the prevention of erosive tooth wear.
Varicose veins are commonly caused by valvular reflux in the saphenous vein. Most insurance companies will approve venous ablation (VA) for the treatment of junctional reflux only and will deny coverage for symptomatic patients with significant nonjunctional reflux of the saphenous vein at the deep system. The present study compared the outcomes of VA for patients with junctional reflux and patients with nonjunctional reflux.
A retrospective, single-center review of consecutive patients who had undergone VA using radiofrequency in an outpatient office was performed from 2012 to 2016. The patients' electronic medical records were reviewed for the characteristics, imaging findings, and outcomes. A telephone survey inquiring about the intensity of symptoms using a numeric rating scale of 0 to 10 before and after treatment was also conducted, with higher number correlating with increasing symptom severity. Patients were grouped according to the location of reflux, either at the saphenofemoral-saphenopoplitealal success rates, technical success rates, and incidence of complications were not different between patients with junctional reflux and those with nonjunctional reflux. The telephone survey was completed by 217 patients after a mean follow-up of 24.9± 11.3months. The survey results demonstrated no differences in improvement in pain or swelling or recurrence of pain or swelling after 2years.
Junctional reflux in the saphenous vein is more likely to be bilateral compared with nonjunctional reflux. The location of reflux did not affect patient presentation or outcomes after VA.
Junctional reflux in the saphenous vein is more likely to be bilateral compared with nonjunctional reflux. The location of reflux did not affect patient presentation or outcomes after VA.
Our aim was to assess the methodologic quality of clinical practice guidelines (CPGs), which inform the diagnosis and management of chronic venous disease (CVD), using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.
A systematic review was performed through the Medline and Embase databases to identify CPGs relevant to CVD. The included articles were evidence-based CPGs available in English and reported in the past 20years. Consensus documents, expert opinions, and studies providing guidance for diagnosis or treatment alone were excluded. Four independent reviewers assessed the CPGs using the AGREE II tool across six domains. Overall quality scaled scores were calculated for each guideline, and the interrater reliability was measured using an intraclass correlation coefficient. SPSS, version 25 (IBM Corp, Armonk, NY) was used for statistical analysis.
Six CPGs reported from 2004 to 2018 were identified; all were of European and North American origin. The interrater reliability when scoring each CPG was high, with an intraclass correlation coefficient of >0.8 (P ≤ .002) for all six CPGs. One CPG had an average score of 95.83% across all domains, qualifying as a high quality CPG. The remaining five CPGs had scores ranging from 29% to 71%. The CPGs generally performed poorly in outlining stakeholder involvement and evaluating the applicability of the guideline to clinical practice.
Scores from the AGREE II tool were reproducible when different users evaluated the CPGs. We identified one CPG for CVD of high methodologic quality. The AGREE II appraisal tool can be used to identify aspects of CPGs that can be developed to improve their methodologic quality.
Scores from the AGREE II tool were reproducible when different users evaluated the CPGs. We identified one CPG for CVD of high methodologic quality. The AGREE II appraisal tool can be used to identify aspects of CPGs that can be developed to improve their methodologic quality.In this paper, a novel procedure for the immobilization and stabilization of enzymes is proposed the multipoint covalent attachment of bi-molecular enzyme aggregates. This immobilization protocol allows the "capture" and fixation of the enzyme aggregate on the support surface. In addition to stabilization by multipoint attachment, enzyme aggregation promotes very interesting stabilizing effects. In the presence of low concentrations of polyethylene glycol (30 %) the dimeric amine oxidase from Pisum sativum forms soluble bi-molecular aggregates. Enzyme aggregates were analyzed by Dynamic Light Scattering and by full chemical loading of a mesoporous support (10 % agarose gels activated with glyoxyl groups). The soluble aggregate was immobilized by multipoint attachment on glyoxyl- agarose at pH 8.5 though the four amino termini of the two dimeric molecules (Lys residues are not reactive at this pH). The immobilized aggregated structure cannot undergo any movement (translational or rotational) after multipoint attachment and the aggregate is "fixed" on the support surface even after the removal of PEG.
