Palovarotene in fibrodysplasia ossificans progressiva: review and perspective.

Introduction: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.

Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease.

A fundamental question in human biology and for hematological disease is how do complex gene-environment interactions lead to individual disease outcome? This is no less the case for sickle cell disease (SCD), a monogenic disorder of Mendelian inheritance, both clinical course, severity, and treatment response, is variable amongst affected individuals. New insight and discovery often lie between the intersection of seemingly disparate disciplines. Recently, opportunities for space medicine have flourished and have offered a new paradigm for study.

Prostate Cancer-related Events in Patients with Synchronous Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate; Data from the HORRAD Trial.

Background And Objective: A survival benefit was demonstrated for patients with low-volume synchronous metastatic hormone-sensitive prostate cancer (mHSPCa) when local radiotherapy to the prostate was added to androgen deprivation therapy. This study aims to determine the incidence of prostate cancer-related events and treatments in those who received and those who did not receive external beam radiotherapy for mHSPCa.

Methods: The HORRAD trial is a multicentre randomised controlled trial recruiting originally 432 patients with mHSPCa diagnosed between 2004 and 2014.

Within-individual changes in physical work demands associated with self-reported health and musculoskeletal symptoms: a cohort study among Dutch workers.

Purpose: This study aimed to investigate changes in physical work demands in association with self-rated health and musculoskeletal symptoms.

Methods: Data from five waves over the period 2019-2021 of the Netherlands Working Conditions Survey COVID-19 were available for 7191 participants aged 19-64 years who worked (partly) on-site during at least two consecutive waves. Logistic generalized estimated equations (GEE) were used to estimate the odds ratios (OR) with 95% confidence interval (CI) for changes (increase or decrease compared to no change) in physical work demands between two waves and poor self-rated health and musculoskeletal symptoms in the following wave, adjusted for the health outcome at the first wave, age, educational level, working hours and hours worked from home.

Future space experiment platforms for astrobiology and astrochemistry research.

Space experiments are a technically challenging but a scientifically important part of astrobiology and astrochemistry research. The International Space Station (ISS) is an excellent example of a highly successful and long-lasting research platform for experiments in space, that has provided a wealth of scientific data over the last two decades. However, future space platforms present new opportunities to conduct experiments with the potential to address key topics in astrobiology and astrochemistry.

Low Transforming Growth Factor-β Pathway Activity in Cervical Adenocarcinomas.

Cervical cancer is the fourth most common cancer in women worldwide. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the most common histological types, with AC patients having worse prognosis. Over the last two decades, incidence rates of AC have increased, highlighting the importance of further understanding AC tumorigenesis, and the need to investigate new treatment options.

Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood pressure (BP). When SGLT2i and GLP-1RA are combined, synergistic effects on BP have been observed. The mechanisms underlying these BP reductions are incompletely understood.

Stability Studies of UV Laser Irradiated Promethazine and Thioridazine after Exposure to Hypergravity Conditions.

Pharmaceuticals carried into space are subjected to different gravitational conditions. Hypergravity is encountered in the first stage, during spacecraft launching. The stability of medicines represents a critical element of space missions, especially long-duration ones.

Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective: A Review.

Importance: Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS.

Observations: Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS.

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial.

Background: A survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT).

Objective: To determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa.

Design, Setting, And Participants: The HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014.

Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy.

Opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapeutics over the past decade. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage IIIC and IV melanoma, who have previously been treated with immunotherapy or targeted therapy. Data was extracted from the Dutch Melanoma Treatment Registry (DMTR) on 154 patients obtaining disease control to systemic therapy and undergoing subsequent surgery.

Coexisting Molecular Determinants of Acquired Oxaliplatin Resistance in Human Colorectal and Ovarian Cancer Cell Lines.

Oxaliplatin (OHP) treatment of colorectal cancer (CRC) frequently leads to resistance. OHP resistance was induced in CRC cell lines LoVo-92 and LoVo-Li and a platinum-sensitive ovarian cancer cell line, A2780, and related to cellular platinum accumulation, platinum-DNA adducts, transporter expression, DNA repair genes, gene expression arrays, and array-CGH profiling. Pulse (4 h, 4OHP) and continuous exposure (72 h, cOHP) resulted in 4.

Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV.

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8-18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status.

Exploring resting state connectivity in patients with psychotic depression.

Background: Severe depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-patients with and without psychotic symptoms.

Feasibility, validity and reliability of objective smartphone measurements of physical activity and fitness in patients with cancer.

Background: A patient's physical function plays a leading role in the treatment prescription for patients with cancer. Objective assessments of physical function may be more predictive for treatment tolerability and survival than frequently used subjective measures, such as the Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance score. The use of smartphones to measure physical activity and fitness may provide an excellent opportunity to objectively estimate a patient's physical function against low costs and little time.