Suhrmelgaard1735

Aim To understand the preferences of US patients and oncologists for PARP inhibitors as second-line maintenance (2LM) for epithelial ovarian cancer. Methods A discrete choice experiment was conducted to assess the preferences of treatment attributes. Results The most valued attributes were risk of grade 3/4 adverse events (AEs; patients, n = 204) and progression-free survival (PFS; oncologists, n = 151). To accept a 37% increased risk of grade 3/4 AEs, PFS would need to increase by 27.9 months (patients) and 6.3 months (oncologists). The least valued attributes were dosing form/frequency (patients) and grade 3/4 anemia risk (oncologists). Conclusion Patients' and oncologists' willingness to make benefit-risk trade-offs in the 2LM setting suggests that the PFS gains observed in selected studies of poly (ADP-ribose) polymerase inhibitors in BRCA-mutated disease are worth the toxicity risk.Inhibition of the PD-1/PD-L1 pathway is a target for the development of new therapies. US10710986 patent describes a small molecule that targets PDL-1/PD-1 interactions and triggers antitumor activity against colorectal cancer. However, it does not describe biological assays that allow us to suppose that this small molecule may be active in other types of cancer. So far, there are no reports of clinical trials to evaluate the safety, toxicity and efficacy, but it will be of great interest to analyze in the future if this compound surpasses the action of therapy in cancer.

During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however.

We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant.

We found that cardiac expression of Gα

, an inhibitory G protein encoded in humans by

, is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of

ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of

in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gα

expression increased surface sarcolemmal L-type Ca

channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca

handling in ventricular myocytes, which led to cardiac dysfunction.

These findings shed light on a novel function of Gα

in the regulation of cardiac Ca

homeostasis and systolic function and suggest Gα

may be an effective therapeutic target for the treatment of heart failure.

These findings shed light on a novel function of Gαo in the regulation of cardiac Ca2+ homeostasis and systolic function and suggest Gαo may be an effective therapeutic target for the treatment of heart failure.Aim To explore the role of RanBP9 in breast cancer. Materials & methods Oncomine, TIMER, GEPIA, UALCAN, c-BioPortal databases and tissue microarray analysis were used in this study. Results The expression level of RanBP9 is elevated in breast cancer tissues, which is associated with poor prognosis in breast cancer patients. RanBP9 exhibits genetic alterations and a decreased methylation level in cancer tissues. RanBP9 may also regulate cell cycle progression and is linked to tumor purity and the infiltrating levels of immune cells. Conclusions RanBP9 may correlate with prognosis and immune infiltration in breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.Aim To explore the effects of viable allogeneic disc tissue supplementation in younger patients with discogenic chronic low back pain (CLBP). Patients & methods VAST was a randomized placebo-controlled trial of disc allograft supplementation in 218 patients with discogenic CLBP. We conducted a post hoc analysis of change from baseline to 12 months in Oswestry Disability Index (ODI) and visual analog scale for pain intensity scores stratified by patient age. Results Patients aged less then 42 years receiving allograft experienced greater improvement in ODI (p = 0.042) and a higher ODI response rate (≥10-, ≥15- and ≥20-point reductions in ODI) than those receiving saline (p = 0.001, p = 0.002 and p = 0.021, respectively). Conclusion Young patients with discogenic CLBP may have significant functional improvement following nonsurgical disc allograft supplementation.

Transgender individuals experience significant oppression resulting in mental health disparities. Factors associated with their need for acute mental health care are unknown. This study compared characteristics of transgender individuals who presented for acute mental health care with population-based comparison samples.

This cross-sectional study examined transgender individuals who had a mental health-related emergency department (ED) visit (N=728) or hospitalization (N=454). Transgender individuals were identified, and their data were linked with health administrative data. The transgender ED and hospitalization samples were each compared with two samples all individuals in Ontario who had an ED visit or hospitalization (unmatched) and individuals matched on age, region of residence, and mental health care utilization history. Individuals' sociodemographic and clinical factors were compared.

After matching, transgender individuals in the ED sample were more likely than those in the comparison group tg. More research into the factors associated with their acute care presentation is warranted, including how experiences of marginalization play a role.

The authors conducted a systematic review of studies evaluating vocational interventions for young people with psychiatric conditions to determine the extent to which services were adapted for young people and whether services promoted gains in postsecondary education and employment.

Five databases (PubMed, PsycINFO, Web of Science, Academic Search Premier, and ERIC) were searched. Sources eligible for inclusion were controlled studies published between 2000 and mid-2020 that evaluated a vocational intervention and examined postsecondary educational or employment outcomes for youths or young adults (ages 14-35 years) with psychiatric conditions.

Ten studies met the inclusion criteria. Several of the studies evaluated services that were adapted for young people, including through the incorporation of educational supports. The most consistent finding was that services based on the individual placement and support (IPS) model improved employment outcomes more effectively than did comparison approaches and include comprehensive educational supports and skills training may be important for efforts to improve postsecondary educational outcomes. Additional well-controlled intervention studies that examine educational and longer-term outcomes should further inform the development and delivery of vocational services for this population.Hub-and-spoke (H&S) partnerships for managing opioid use disorder vary by U.S. AM152 state. This column provides the first description of the development of an H&S partnership in Tennessee, a Medicaid nonexpansion state. Medicaid expansion allows states to fund evidence-based substance use disorder treatment and community-based psychosocial interventions. In an H&S model in a Medicaid nonexpansion context, federal grant support must fund not only treatment itself but also the creation and maintenance of parallel billing and documentation processes for various partners, reducing the funds available for patient care.

Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events.

Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate.

We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43-54 mm) and median follow-up of 914 (interquartile range, 670-1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experies, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.

Ischemic stroke is a common cause of death in adults, however, mortality after pediatric ischemic stroke is not well explored. We investigate long-term and cause-specific mortality in children with ischemic stroke and their first-degree relatives.

Through nationwide Swedish registers, we identified 1606 individuals <18 years old with ischemic stroke between 1969 and 2016 and their first-degree relatives (n=5714). Each individual with ischemic stroke was compared with 10 reference individuals (controls) matched for age, sex, and county of residence. Our main analysis examined 1327 children with ischemic stroke still alive 1 week after the event. First-degree relatives to children with ischemic stroke were compared with first-degree relatives to the reference individuals. Using a Cox proportional hazard regression model, the risk of overall and cause-specific mortality was computed in individuals with pediatric ischemic stroke and their first-degree relatives.

The mortality rate in the first 6 months wortality increased after pediatric ischemic stroke, even 20 years later, with neurological diseases as the most frequent cause of death.Film wound dressings represent one of the options in wound therapy. Various polymers can be used for their production. Currently, research focuses on materials of natural origin, more friendly to the human body, which are in many cases able to participate actively in the wound healing process. These include polyamino acids of bacterial origin, substances that are biodegradable, non-toxic, and have a great potential for an application not only in the medical field. From the point of view of film wound dressing formulation, poly-γ-glutamic acid (PGA), as a film-forming agent, and poly-ε-lysine (PL), characterized by antimicrobial activity, are of interest from this group. Therefore, the aim of our experiment was to prepare films consisting of PGA or a combination of PGA and PL with the addition of different plasticizers. The films were prepared by solvent evaporation method and then evaluated for their organoleptic (appearance, colour, transparency, ease of handling), physicochemical (thickness, density, opacity, surface pH), and mechanical properties (tensile strength and tear resistance).