Toward Dose Prediction at Point of Design.

Human dose prediction (HDP) is a useful tool for compound optimization in preclinical drug discovery. We describe here our exclusively in silico HDP strategy to triage compound designs for synthesis and experimental profiling. Our goal is a model that provides a preliminary estimate of the dose for a given exposure target based on chemical structure.

Results after Four Years of Screening for Prostate Cancer with PSA and MRI.

Background: Data on the efficacy and safety of screening for prostate cancer with magnetic resonance imaging (MRI) are needed from studies of follow-up screening.

Methods: In a population-based trial that started in 2015, we invited men who were 50 to 60 years of age to undergo prostate-specific antigen (PSA) screening. Men with a PSA level of 3 ng per milliliter or higher underwent MRI of the prostate.

The TβRI promotes migration and metastasis through thrombospondin 1 and ITGAV in prostate cancer cells.

TGFβ potently modifies the extracellular matrix (ECM), which is thought to favor tumor cell invasion. However, the mechanism whereby the cancer cells employ the ECM proteins to facilitate their motility is largely unknown. In this study we used RNA-seq and proteomic analysis to examine the proteins secreted by castration-resistant prostate cancer (CRPC) cells upon TGFβ treatment and found that thrombospondin 1 (THBS1) was observed to be one of the predominant proteins.

Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging.

Background And Purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

Environmental bacterial load during surgical and ultrasound procedures in a Swedish small animal hospital.

Background: Environmental bacteria in animal healthcare facilities may constitute a risk for healthcare-associated infections (HAI). Knowledge of the bacterial microflora composition and factors influencing the environmental bacterial load can support tailored interventions to lower the risk for HAI. The aims of this study were to: (1) quantify and identify environmental bacteria in one operating room (OR) and one ultrasound room (UR) in a small animal hospital, (2) compare the bacterial load to threshold values suggested for use in human healthcare facilities, (3) characterise the genetic relationship between selected bacterial species to assess clonal dissemination, and (4) investigate factors associated with bacterial load during surgery.

A swallowing and breastfeeding intervention programme for small and sick neonates embedded in kangaroo mother care.

Available evidence of oral sensorimotor interventions for small neonates is not strong. Evidence of interventions for sick term neonates is largely lacking. Studies are limited by risk of bias and inconsistency.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study.

Purpose: The aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events.

Materials And Methods: Blood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters.

Results: HS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.

Effects of a physical exercise programme on bodyweight, body condition score and chest, abdominal and thigh circumferences in dogs.

Background: Research on the effects of physical exercise on canine body composition is limited. The aim of this study was to investigate the effects of a physical exercise programme on bodyweight, body condition score (BCS) and chest, abdominal and thigh circumferences in dogs. Twenty-one healthy dogs of different breeds exercised together with their owners during an eight-week programme consisting of jogging and strength exercises.

Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer.

Background: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

A pilot study of a joint outdoor exercise program for dog owners and dogs.

Increasing levels of physical inactivity is a global burden for mankind and is also an emerging problem in companion dogs. In both humans and dogs, insufficient physical activity is associated with increased risk for noncommunicable diseases and impaired quality of life (QoL). The aim of the current pilot study was to evaluate effects of a joint outdoor exercise program for dog owners (n = 22) and dogs (n = 22) with focus on QoL and body measurements.

Effect of Transcutaneous Electrical Nerve Stimulation on Gait Parameters in Dogs with Osteoarthritis.

Osteoarthritis is a common degenerative disease in dogs, often manifested as pain, joint swelling, and lameness. Despite the lack of scientific evidence for its treatment efficacy, transcutaneous electrical nerve stimulation (TENS) is used in dogs as a pain-relieving treatment. This randomised single-blinded cross-over study investigated the effect of TENS on gait parameters in fifteen dogs with osteoarthritis.

Overall survival benefit of androgen suppression in addition to dose-escalated external beam radiotherapy for high-risk prostate cancer: Nationwide real-world data indicates a shift in men that benefit.

Objective: To evaluate the real-world added value of androgen deprivation therapy (ADT) in addition to external beam radiotherapy (EBRT) in men with high-risk non-metastatic prostate cancer, in view of advances in radiotherapy and diagnostics.

Methods: All Dutch men diagnosed with high-risk non-metastatic prostate cancer (defined as: ≥cT2c-T3b N0M0, PSA ≥20-50 ng/ml, and/or Gleason score ≥8 (International Society of Urological Pathology [ISUP] grade ≥4)) from 2009 through 2019 and treated with EBRT with or without ADT were identified in the population-based Netherlands Cancer Registry. Propensity scores were used to match (1:1) men that received ADT to men that did not receive ADT.

Novel insights into the host cell glycan binding profile of human metapneumovirus.

Numerous viruses have been found to exploit glycoconjugates expressed on human cells as their initial attachment factor for viral entry and infection. The virus-cell glycointeractome, when characterized, may serve as a template for antiviral drug design. Heparan sulfate proteoglycans extensively decorate the human cell surface and were previously described as a primary receptor for human metapneumovirus (HMPV).

[Molecular subtypes provide possibilities for precision medicine in a advanced prostate cancer].

Increased molecular knowledge makes it possible to consider not only genetic defects but also expression profiles for precision medicine in advanced prostate cancer. Several prognostic and treatment-predictive classifiers for prostate cancer have been described, such as Prolaris, OncotypeDx, Decipher, Prostatype, PAM50, PCS1-2, and MetA-C, which all build upon transcript profiles. In research studies, the MetA-C classifier has shown clear prognostic information for patients with metastatic disease, in relation to outcome after androgen receptor targeting therapies, and so has immunohistochemical evaluation of tumor cell proliferation (Ki67) and PSA expression.

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Extrapulmonary tuberculosis (TB) in the gastrointestinal tract is a rare, but yet an essential differential diagnosis to patients with complex fistula disease, since the initiation of immunosuppressive therapy for presumed Crohn's disease can lead to a fulminant course of TB. This case report presents a young Danish woman with a progressive complex fistula disease, where cause and treatment were uncovered by interprofessional collaboration between pulmonologists, gastroenterologists and surgeons including a screening test for TB as well as multiple biopsies from the anal fistula tissue.

Metabolomic profiles of intact tissues reflect clinically relevant prostate cancer subtypes.

Background: Prostate cancer (PC) is a heterogenous multifocal disease ranging from indolent to lethal states. For improved treatment-stratification, reliable approaches are needed to faithfully differentiate between high- and low-risk tumors and to predict therapy response at diagnosis.

Methods: A metabolomic approach based on high resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) analysis was applied on intact biopsies samples (n = 111) obtained from patients (n = 31) treated by prostatectomy, and combined with advanced multi- and univariate statistical analysis methods to identify metabolomic profiles reflecting tumor differentiation (Gleason scores and the International Society of Urological Pathology (ISUP) grade) and subtypes based on tumor immunoreactivity for Ki67 (cell proliferation) and prostate specific antigen (PSA, marker for androgen receptor activity).

The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography.

Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.

In uncharted territory "together each achieves more": a United Nations interagency collaboration for continuity of maternal and newborn health services during the coronavirus pandemic in the Eastern and Southern Africa region.

The frangible collaboration between three United Nations agencies (UNICEF, UNFPA and WHO) in the Eastern and Southern Africa Region was strengthened by the outbreak of the coronavirus pandemic. The aim was to combine existing resources and expertise to support countries to respond to the pandemic more effectively and efficiently regarding the provision of maternal and newborn health services. Three kinds of activities were conducted: 15 webinars on a variety of topics and issues impacted by the pandemic; virtual training on maternal and perinatal death surveillance and response as well as on quality improvement; and the development of online e-learning modules for continuous professional development.

Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer.

Background: For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers.

Roles and Responsibilities in the Transition to Working Independently: A Qualitative Study of Recently Graduated Radiographers' Perspectives in Australia.

Background: Medical imaging features along the entire healthcare continuum and is known for its fast-paced technological evolution which enables it to keep up with the demands of the healthcare system to provide safe, quality services. The overall efficacy and efficiency of the system depends on practitioners' clinical competence, achieved through professional education and continuous professional development. Recent studies have revealed concerns regarding newly graduated healthcare professionals' preparedness and readiness to handle actual practice.

Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [ 68 Ga]PSMA-11-PET and [ 11 C]Acetate-PET.

Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [ 68 Ga]PSMA-11-PET (PSMA)-PET, [ 11 C]Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.

Implementation of continuous-wave Doppler ultrasound to detect the high-risk foetus in the low-risk mother: lessons from South Africa.

Introduction: Detecting the risk of stillbirth during pregnancy remains a challenge. Continuous-wave Doppler ultrasound (CWDU) can be used to screen for placental insufficiency, which is a major cause of stillbirths in low-risk pregnant women. This paper describes the adaptation and implementation of screening with CWDU and shares critical lessons for further rollout.

Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328.

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases ( = 14), localized PC ( = 7) and benign prostate tissue ( = 7).