Qualitative Bereavement Experiences and Support in Community-Dwelling Older Adults: A Scoping Review.

This scoping review examines qualitative studies on bereavement experiences and support mechanisms for community-dwelling older adults. This area of research is especially timely given rapid population aging and the interplay of heightened vulnerability, cumulative losses, shrinking support systems, and the critical need for bereavement support. Such support not only acts as a preventative health measure but can also serve as a catalyst for fostering meaning-making and navigating grief in later life.

A cross-sectional comparison of gut metagenomes between dairy workers and community controls.

Background: As a nexus of routine antibiotic use and zoonotic pathogen presence, the livestock farming environment is a potential hotspot for the emergence of zoonotic diseases and antibiotic resistant bacteria. Livestock can further facilitate disease transmission by serving as intermediary hosts for pathogens before a spillover event. In light of this, we aimed to characterize the microbiomes and resistomes of dairy workers, whose exposure to the livestock farming environment places them at risk for facilitating community transmission of antibiotic resistant genes and emerging zoonotic diseases.

Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial.

Background: Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain.

Aging Parents and the Ties That Bind: Intergenerational Relationship Quality Among Culturally Diverse Canadian Families.

Drawing from a life course perspective, this paper examines mid/later-life parent-child relationship quality among ethnically diverse families. Focus is on the role of culture, child, and parental characteristics. Data are drawn from a study of 588 parents aged 50+ of a least one child aged 19-35 who reside in Metro Vancouver, B.

Analyzing microbial evolution through gene and genome phylogenies.

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories.

Analyzing microbial evolution through gene and genome phylogenies.

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories.

Neutrophil-to-Lymphocyte Ratio and Outcomes in Patients Admitted for Acute Heart Failure (As Seen in the BLAST-AHF, Pre-RELAX-AHF, and RELAX-AHF Studies).

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis.

COVID-19 and social work in health care in Canada: What are the impacts?

The COVID-19 pandemic has profoundly affected the world. In Canada, the impact has been worrisome. Canada is a large, sparsely populated country with a system of universal health care that is decided nationally and enacted by each province and territory.

DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.

T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs).

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial.

Aims: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction.

Methods And Results: We studied the effects of danicamtiv on LV and LA function in non-clinical studies (ex vivo: skinned muscle fibres and myofibrils; in vivo: dogs with heart failure) and in a randomized, double-blind, single- and multiple-dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50-100 mg twice daily for 7 days).

Effects of serelaxin in patients admitted for acute heart failure: a meta-analysis.

Aims: The effectiveness and safety of 48 h intravenous 30 μg/kg/day serelaxin infusion in acute heart failure (AHF) has been studied in six randomized, controlled clinical trials.

Methods And Results: We conducted a fixed-effect meta-analysis including all studies of intravenous serelaxin initiated within the first 16 h of admission for AHF. Endpoints considered were the primary and secondary endpoints examined in the serelaxin phase III studies.

Improved long-term patient-reported health and well-being outcomes of early-stage breast cancer treated with partial breast proton therapy.

Background: Because early-stage breast cancer can be treated successfully by a variety of breast-conservation approaches, long-term quality of life (QoL) is an important consideration in assessing treatment outcomes for these patients. This study compares patient-reported QoL outcomes among women with stage 0-2 disease treated via lumpectomy followed by whole breast irradiation (WBI) or partial breast proton irradiation (PBPT).

Methods: In this cross-sectional study, 129 participants evaluated QoL several years post-treatment by responding to subjective instruments, including established scalar questionnaires and self-report measures.

Translation of Cardiac Myosin Activation with 2-deoxy-ATP to Treat Heart Failure via an Experimental Ribonucleotide Reductase-Based Gene Therapy.

Despite recent advances, chronic heart failure remains a significant and growing unmet medical need, reaching epidemic proportions carrying substantial morbidity, mortality, and costs. A safe and convenient therapeutic agent that produces sustained inotropic effects could ameliorate symptoms, and improve functional capacity and quality of life. We discovered small amounts of 2-deoxy-ATP (dATP) activate cardiac myosin leading to enhanced contractility in normal and failing heart muscle.

Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

Background: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.

Methods: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4.

Cardiac Myosin Activation with Gene Therapy Produces Sustained Inotropic Effects and May Treat Heart Failure with Reduced Ejection Fraction.

Chronic inotropic therapy is effective for the treatment of heart failure with reduced ejection fraction, but has been limited by adverse long-term safety profiles, development of tolerance, and the need for chronic parenteral administration. A safe and convenient therapeutic agent that produces sustained inotropic effects could improve symptoms, functional capacity, and quality of life. Small amounts of 2-deoxy-adenosine triphosphate (dATP) activate cardiac myosin leading to enhanced contractility in normal and failing heart muscle.

Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure.

Aims: Heart failure remains a leading cause of morbidity, hospitalizations, and deaths. We previously showed that overexpression of the enzyme ribonucleotide reductase (RNR) in cardiomyocytes increased levels of the myosin activator, 2-deoxy-ATP, catalysed enhanced contraction, and improved cardiac performance in rodent hearts. Here we used a swine model of myocardial infarction (MI) to test preliminarily a novel gene therapy for heart failure based on delivery of the human RNR enzyme complex under the control of a cardiac-specific promoter via an adeno-associated virus serotype 6 vector--designated as BB-R12.

Challenges in acute heart failure clinical management: optimizing care despite incomplete evidence and imperfect drugs.

Acute heart failure is a common condition associated with considerable morbidity, mortality, and cost. However, evidence-based data on treating heart failure in the acute setting are limited, and current individual treatment options have variable efficacy. The healthcare team must often individualize patient care in ways that may extend beyond available clinical guidelines.

Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial.

Background: A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly.

Methods: We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.

Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes.

Objectives: The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure.

Background: Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage.

Methods: The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin.

Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial.

Background: Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo.

Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression.

Context: Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity.

Objectives: The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection.

Design: Four single-dose studies were conducted in 75 healthy volunteers.

Conserved asparagine residue located in binding pocket controls cation selectivity and substrate interactions in neuronal glutamate transporter.

Transporters of the major excitatory neurotransmitter glutamate play a crucial role in glutamatergic neurotransmission by removing their substrate from the synaptic cleft. The transport mechanism involves co-transport of glutamic acid with three Na(+) ions followed by countertransport of one K(+) ion. Structural work on the archeal homologue Glt(Ph) indicates a role of a conserved asparagine in substrate binding.

Design of the RELAXin in acute heart failure study.

Background: Acute heart failure (AHF) remains a major public health burden with a high prevalence and poor prognosis. Relaxin is a naturally occurring peptide hormone that increases cardiac output, arterial compliance, and renal blood flow during pregnancy. The RELAX-AHF-1 study will evaluate the effect of RLX030 (recombinant form of human relaxin 2) on symptom relief and clinical outcomes in patients with AHF.

Early drop in systolic blood pressure and worsening renal function in acute heart failure: renal results of Pre-RELAX-AHF.

Aims: We aimed to determine the relation between baseline systolic blood pressure (SBP), change in SBP, and worsening renal function (WRF) in acute heart failure (AHF) patients enrolled in the Pre-RELAX-AHF trial.

Methods And Results: The Pre-RELAX-AHF study enrolled 234 patients within 16 h of admission (median 7 h) for AHF and randomized them to relaxin given intravenous (i.v.