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to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly.

Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited.

ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. D-AP5 chemical structure We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS.

A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p =0.039), with no difference between OCT and IVUS (p =0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93 p =0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p =0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found.

Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.

Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplant Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from 7/18/2019 - 7/15/2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and one year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.Somatic mutations in isocitrate dehydrogenase1 (IDH1) gene1-3 are common in Ollier disease and in several neoplasms including cholangiocarcinoma. We report the case of a woman with Ollier disease with chondrosarcomas and an anaplastic astrocytoma. A mutation in IDH1 was found causing R132H at the protein level in both tumors. At the age of 40, the patient presented an acute abdominal pain.Carotenoids are lipophilic substances with many biological functions, from coloration to photoprotection. Being potent antioxidants, carotenoids have multiple biomedical applications, including the treatment of neurodegenerative disorders and retina degeneration. Nevertheless, the delivery of carotenoids is substantially limited by their poor solubility in the aqueous phase. Natural water-soluble carotenoproteins can facilitate this task, necessitating studies on their ability to uptake and deliver carotenoids. One such promising carotenoprotein, AstaP (astaxanthin-binding protein), was recently identified in eukaryotic microalgae, but its structure and functional properties remained largely uncharacterized. By using a correctly folded recombinant protein, here we show that AstaP is an efficient carotenoid solubilizer that can stably bind not only astaxanthin but also zeaxanthin, canthaxanthin, and, to a lesser extent, β-carotene, that is, carotenoids especially valuable to human health. AstaP accepts carotenoids provided as acetone solutions or embedded in membranes, forming carotenoid-protein complexes with an apparent stoichiometry of 11. We successfully produced AstaP holoproteins in specific carotenoid-producing strains of Escherichia coli, proving it is amenable to cost-efficient biotechnology processes. Regardless of the carotenoid type, AstaP remains monomeric in both apo- and holoform, while its rather minimalistic mass (~ 20 kDa) makes it an especially attractive antioxidant delivery module. In vitro, AstaP transfers different carotenoids to liposomes and to unrelated proteins from cyanobacteria, which can modulate their photoactivity and/or oligomerization. These findings expand the toolkit of the characterized carotenoid binding proteins and outline the perspective of the use of AstaP as a unique monomeric antioxidant nanocarrier with an extensive carotenoid binding repertoire.

Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection.

A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969-1989 over a 10-year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV-Ab) detection followed by HCV-RNA or HCV core antigen (HCV-Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients' drop-off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratios (ICER).

The reference option was Rapid HCV-Ab followed by second sample HCV-Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV-RNA reflex testing which produced a high cost-effective ICER (€891/QALY). Reflex testing (same sample-single visit) vs two patients' visits algorithms, yielded the highest QALYs and high cost-effective ICERs (€566 and €635/QALY for HCV-Ag and HCV-RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations.

Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.

Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.Bruton's tyrosine kinase (BTK) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage. Evidence has shown that inhibition of BTK has clinical benefit for the treatment of a wide array of autoimmune and inflammatory diseases. Previously we reported the discovery of a novel nicotinamide selectivity pocket (SP) series of potent and selective covalent irreversible BTK inhibitors. The top molecule 1 of that series strongly inhibited CYP2C8 (IC50 =100 nM), which was attributed to the bridged linker group. However, our effort on the linker replacement turned out to be fruitless. With the study of the X-ray crystal structure of compound 1, we envisioned the opportunity of removal of this liability via transposition of the linker moiety in 1 from C6 to C5 position of the pyridine core. With this strategy, our optimization led to the discovery of a novel series, in which the top molecule 18 A displayed reduced CYP inhibitory activity and good potency. To further explore this new series, different warheads besides acrylamide, for example cyanamide, were also tested. However, this effort didn't lead to the discovery of molecules with better potency than 18 A. The loss of potency in those molecules could be related to the reduced reactivity of the warhead or reversible binding mode. Further profiling of 18 A disclosed that it had a strong hERG (human Ether-a-go-go Related Gene) inhibition, which could be related to the phenoxyphenyl group.

To investigate the effects of cortical bone thickness (CBT), miniscrew implant root proximity (MRP) and other related factors on the success rate of miniscrew implant (MSI).

405 MSIs placed in 171 patients were analysed in this retrospective study. The primary predictor variables were CBT and MRP at MSI insertion sites. The predictor variable also included patient, location, MSI design and procedure related factors. The outcome variable was the survival of MSI. The differences in measurement data between success group and failed group were evaluated by the analysis of variance and independent samples t tests. Patient, location, MSI design and procedure related factors associated with the MSI prognosis were analysed by survival analysis with Cox proportional hazard regression model. The P value was set at 0.05. And the survival curves of independent factors were plotted.

The overall success rate of MSI was 82.7%. The age of MSI host, CBT, interdental root distance and MRP at MSI sites showed no significant differences between failed group and success group. CBT and insertion jaws were independent prognosis factors screened out by Cox proportional hazard regression model. Failure risk of MSI with CBT <1 mm was about 4.72. The risk of failure in the mandible was 3.80 times as high as in the maxilla.

Inadequate CBT (<1 mm) contributed to the failure of MSI. MSI placed in the maxilla showed better prognosis compared to the mandible. MRP had no significant effect on the prognosis.

Inadequate CBT ( less then 1 mm) contributed to the failure of MSI. MSI placed in the maxilla showed better prognosis compared to the mandible. MRP had no significant effect on the prognosis.

This secondary analysis examined physical activity (PA) changes and their prognostic significance among Latinx patients with obesity, with and without binge eating disorder (BED), who participated in a randomized, placebo-controlled trial testing the addition of orlistat to behavioral weight-loss (BWL) treatment in a "real-world" clinical setting.

In this randomized controlled trial at a community mental health center serving economically disadvantaged Spanish-speaking-only Latinx patients, 79 patients with obesity (40 with BED and 39 without BED) received BWL treatment and were randomized to orlistat or placebo. PA, weight, depression, and binge eating were assessed at baseline, posttreatment (end of treatment [4 months]), and the 6-month follow-up (10 months after baseline).

PA was low at baseline (9.3% categorized as "active"), increased during treatment (32.9% categorized as "active" at posttreatment), and declined from posttreatment to the 6-month follow-up (28.2% classified as "active"). At baseline, PA was lower among patients with BED than those without BED.