Transient impact of chronic social stress on effort-based reward motivation in non-food restricted mice: Involvement of corticosterone.

Chronic stress has been connected to a reduced effort and motivational deficits. To study effort-based motivation in rodents, operant conditioning is often employed. However, caloric restriction is typically imposed simultaneously.

Adaptations in hepatic glucose metabolism after chronic social defeat stress in mice.

Chronic stress has been shown to induce hyperglycemia in both peripheral blood and the brain, yet the detailed mechanisms of glucose metabolism under stress remain unclear. Utilizing C-labeled glucose to trace metabolic pathways, our study investigated the impact of stress by chronic social defeat (CSD) on glucose metabolites in the liver and brain one week post-stress. We observed a reduction in C-enrichment of glucose metabolites in the liver, contrasting with unchanged levels in the brain.

Monitoring autumn agriculture activities using Synthetic Aperture Radar (SAR) and coherence change detection.

Across Canada, farmers are encouraged to adopt beneficial management practices (BMPs) to protect soil heath, reduce green house gas emissions and mitigate off-site impacts from agriculture. Measuring the uptake of BMPs, including the implementation of conservation tillage, helps gauge the success of policies and programs to promote adoption. Satellites are one way to monitor BMP adoption and Synthetic Aperture Radars (SARs) are of particular interest given their all-weather data collection capability.

Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry.

Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry.

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side-effects based on the Grading of Recommendations Assessment, Development, and Evaluation system. As these drugs have been used for a relatively short time, large systematic investigations are scarce.

Nutritional follow-up in children after discharge: Organisation in a tertiary care centre.

Background: Aiming to improve the standard of care for patients with a nutritional intervention, we evaluated how nutritional follow-up (FU) is organised at discharge and after 6 months.

Methods: From 16 November 2020 until 20 December 2020, we retrospectively included patients admitted for > 1 day to the general ward of a tertiary hospital. Medical charts were reviewed for demographics, anthropometric measurements and nutritional interventions (e.

Chronic social stress disrupts the intracellular redistribution of brain hexokinase 3 induced by shifts in peripheral glucose levels.

Chronic stress has the potential to impair health and may increase the vulnerability for psychiatric disorders. Emerging evidence suggests that specific neurometabolic dysfunctions play a role herein. In mice, chronic social defeat (CSD) stress reduces cerebral glucose uptake despite hyperglycemia.

A Pharmacy-Based eHealth Intervention Promoting Correct Use of Medication in Patients With Asthma and COPD: Nonrandomized Pre-Post Study.

Background: Asthma and chronic obstructive pulmonary disease (COPD) affect millions of people worldwide. While medication can control and improve disease symptoms, incorrect use of medication is a common problem. The eHealth intervention SARA (Service Apothecary Respiratory Advice) aims to improve participants' correct use of inhalation medication by providing information and as-needed tailored follow-up support by a pharmacist.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial.

Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response.

Transition of care in stroke patients discharged home: a single-center prospective cohort study.

Introduction: Approximately two-thirds of the patients admitted to the hospital with an ischemic stroke are discharged directly home. Discontinuity of care may result in avoidable patient harm, re-admissions and even death. We hypothesized that the transfer of information is most essential in this patient group since any future care for these patients relies solely on the information that is available to the care provider responsible at that time.

Longitudinal CSF proteome profiling in mice to uncover the acute and sustained mechanisms of action of rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK).

Delayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapid-acting antidepressants. However, their mechanism of action remains unknown.

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study.

Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013-July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3-4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable.

Effects of a transitional care programme on medication adherence in an older cardiac population: A randomized clinical trial.

Aims: Medication non-adherence post-discharge is common among patients, especially those suffering from chronic medical conditions, and contributes to hospital admissions and mortality. This study aimed to evaluate the effect of the Cardiac Care Bridge (CCB) intervention on medication adherence post-discharge.

Methods: We performed a secondary analysis of the CCB randomized single-blind trial, a study in patients ≥70 years, at high risk of functional loss and admitted to cardiology departments in six hospitals.

Incorporating inter-individual variability in experimental design improves the quality of results of animal experiments.

Inter-individual variability in quantitative traits is believed to potentially inflate the quality of results in animal experimentation. Yet, to our knowledge this effect has not been empirically tested. Here we test whether inter-individual variability in emotional response within mouse inbred strains affects the outcome of a pharmacological experiment.

Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Na) channels properties.

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells.

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients.

Background: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort.

Methods: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome.

Chronic social stress lessens the metabolic effects induced by a high-fat diet.

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high-fat diet (HFD), aggravates the metabolic phenotype and whether there are particularly sensitive time windows for the negative consequences of HFD exposure.

Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease : A Cohort Study.

Background: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials.

Objective: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID.

Design: Nationwide cohort study.

[Exchange of information between psychiatrist and pharmacist concerning uncollected medication].

Background Non- compliance with drug regimens has a negative effect on symptomatology and is the largest predictor of relapse in people with Severe Psychiatric Disorder (EPA). When care providers are informed in good time that medication has not been collected and can act on it, compliance can be increased. Aim Assessment of usefulness and feasibility of a system for the Signaling and Reporting by Pharmacists of Uncollected Medication for people with an EPA (Dutch: 'SMANOM-EPA') within the current legal context.

A distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cells.

Major depressive disorder is the most prevalent mental illness worldwide, still its pharmacological treatment is limited by various challenges, such as the large heterogeneity in treatment response and the lack of insight into the neurobiological pathways underlying this phenomenon. To decode the molecular mechanisms shaping antidepressant response and to distinguish those from general paroxetine effects, we used a previously established approach targeting extremes (i.e.

Phase I/II study protocol to assess safety and efficacy of adoptive cell therapy with anti-PD-1 plus low-dose pegylated-interferon-alpha in patients with metastatic melanoma refractory to standard of care treatments: the ACTME trial.

Introduction: Treatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.

Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response.

Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15-39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3-4 adverse events (AEs), responses and outcomes in AYAs ( = 210) and older adults ( = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018.

The impact of chronic stress on energy metabolism.

The brain is exceptionally demanding in terms of energy metabolism. Approximately 20% of the calories consumed are devoted to our cerebral faculties, with the lion's share provided in the form of glucose. The brain's stringent energy dependency requires a high degree of harmonization between the elements responsible for supplying- and metabolizing energetic substrates.