A Case Report of Metastatic Castration-Resistant Prostate Cancer Harboring a \u3ci\u3ePTEN\u3c/i\u3e Loss

The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has dramatically improved over the last decade; however, patients with visceral metastases are still faced with poor outcomes. Phosphatase and tensin homolog (PTEN) loss is observed in 40%–60% of mCRPC patients and is also associated with a poor prognosis. Several PI3K/AKT/mTOR pathway inhibitors have been studied, with disappointing anti-tumor activity. Here, we present a case of a patient with heavily treated mCRPC who had a modest tumor response to concurrent carboplatin, abiraterone acetate/prednisone, and liver-directed radiation therapy. We discuss the potential rationale supporting the use of this combination therapy and its safety in mCRPC. While the underlying basic mechanism of our patient’s anti-tumor response remains uncertain, we suggest that further prospective studies are warranted to evaluate whether this combination therapy is effective in this population of patients with pre-treated mCRPC and PTEN loss

Hyperonic mixing in five-baryon double-strangeness hypernuclei in a two-channel treatment

Properties of hypernuclei $_{\Lambda \Lambda}^5$H and $_{\Lambda \Lambda }^5$He are studied in a two-channel approach with explicit treatment of coupling of channels ^3\text{Z}+\Lambda+\Lambda and \alpha+\Xi. Diagonal \Lambda\Lambda and coupling \Lambda\Lambda-\Xi N interactions are derived within G-matrix procedure from Nijmegen meson-exchange models. Bond energy \Delta B_{\Lambda\Lambda} in $_{\Lambda \Lambda}^5$He exceeds significantly that in $_{\Lambda \Lambda}^5$H due to the channel coupling. Diagonal \Xi\alpha attraction amplifies the effect, which is sensitive also to \Lambda-core interaction. The difference of the \Delta B_{\Lambda\Lambda} values can be an unambiguous signature of the \Lambda\Lambda-\Xi N coupling in \Lambda\Lambda hypernuclei. However, improved knowledge of the hyperon-nucleus potentials is needed for quantitative extraction of the coupling strength from future data on the \Lambda\Lambda hypernuclear binding energies.Comment: 11 pages with 3 figures; Phys. Rev. C, accepte

Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms

Protocol for a scoping review on information needs and information-seeking behaviour of people with dementia and their non-professional caregivers

Background: Dementia is a debilitating disease that can lead to major changes in a patient’s behaviour and function. It is important to educate both dementia patients and their non-professional caregivers about the disease. Yet, currently available sources do not seem to be effective for patients and caregivers, who report a need for more information and guidance. A systematic identification of the patients’ and caregivers’ needs for information and information seeking behaviour is needed to create information resources that are relevant and beneficial to the target population. Objective: This is a protocol for a scoping review aimed at gathering knowledge on the information needs and information seeking behaviour of dementia patients and their non- professional caregivers. Our aim is also to provide recommendations for development of future dementia information resources. Methods: The study will commence in November 2018. Both quantitative and qualitative studies on the information needs of dementia patients or caregivers will be examined using Arksey and O’Malley’s methodological framework for scoping studies. A comprehensive literature search will be conducted in electronic databases and grey literature sources. We will also screen reference lists of included studies and related systematic reviews for additional eligible studies. Two authors will perform screening of citations for eligibility, and independently extract data from the included studies in parallel. Any discrepancies will be resolved through discussion. The findings will be presented through a narrative synthesis and reported in line with PRISMA reporting guidelines. Ethics and dissemination: In this review, all included data will originate from published literature. Ethics approval is therefore not a requirement. We will present our findings at relevant conferences and will submit them for publication in peer-reviewed journals. Strengths and limitations of this study • In this scoping review, we will perform a comprehensive search of electronic databases and grey literature sources to identify up-to-date evidence on information needs and information seeking behaviour of dementia patients and their informal caregivers. • We will seek to identify evidence on information needs and information seeking behaviour of both dementia patients and their caregivers. • As this is a scoping review, a formal quality and risk of bias assessment of the included literature will not be performed. • This review will only include studies published in English

Co-regularised support vector regression

We consider a semi-supervised learning scenario for regression, where only few labelled examples, many unlabelled instances and different data representations (multiple views) are available. For this setting, we extend support vector regression with a co-regularisation term and obtain co-regularised support vector regression (CoSVR). In addition to labelled data, co-regularisation includes information from unlabelled examples by ensuring that models trained on different views make similar predictions. Ligand affinity prediction is an important real-world problem that fits into this scenario. The characterisation of the strength of protein-ligand bonds is a crucial step in the process of drug discovery and design. We introduce variants of the base CoSVR algorithm and discuss their theoretical and computational properties. For the CoSVR function class we provide a theoretical bound on the Rademacher complexity. Finally, we demonstrate the usefulness of CoSVR for the affinity prediction task and evaluate its performance empirically on different protein-ligand datasets. We show that CoSVR outperforms co-regularised least squares regression as well as existing state-of-the-art approaches for affinity prediction

Blood pressure differences between home monitoring and daytime ambulatory values and their reproducibility in treated hypertensive stroke and TIA patients

Background: Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups. Methods: Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted. Results: Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was −6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was −7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were −2.1 ± 8.5mm Hg (P=.03) and −2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were −33.0 to 19.9mm Hg and −28.7 to 14.5mm Hg for the 2 comparisons and for DBP were −18.8 to 14.5mm Hg and −16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified. Conclusions: Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease

Preoperative Kidney Function linked to mortality and readmission outcomes at Day 90 and 30 in Older Emergency Surgical Patients

Grants were received from British Geriatric Society and The Renal Association to support Louis EvansPeer reviewedPublisher PD

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814

In-hospital Outcomes of Acute Ischaemic Stroke Patients with Atrial Septal Defect. : A National Inpatient Sample Study.

Acknowledgements We would like to acknowledge the HCUP Data Partners (https://www.hcup10 us.ahrq.gov/db/hcupdatapartners.jsp). Sources of Funding FC received the Leslie Wilson Endowed Scholarship as a part of the Aberdeen Summer Research Scholarship Programme of the Aberdeen Clinical Academic Training (ACAT) Pathways. The Leslie Wilson Endowed Scholarship is funded by Department of Medicine for the Elderly, NHS Grampian.Peer reviewedPostprin