Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with FSGS in a US Real-World Database.

Key Points: In our patients with FSGS, elevated proteinuria and progression to kidney failure (KF) were associated with a higher risk of cardiovascular disease/all-cause mortality events. In addition, elevated pre-KF proteinuria was associated with KF/all-cause mortality events. CKD stage, nephrotic syndrome, and cardiovascular disease event rates, as well as the incremental costs of these events, were high.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States.

Study Design: Retrospective cohort study.

Humanistic and Economic Burden of IgA Nephropathy: Systematic Literature Reviews and Narrative Synthesis.

Background: Immunoglobulin A nephropathy (IgAN) is a progressive inflammatory kidney disease requiring long-term treatment to reduce the risk of progression to kidney failure. Here, we present two systematic literature reviews (SLRs) to identify and summarize literature reporting the humanistic and economic burden of IgAN.

Methods: Electronic literature databases (Ovid Embase, PubMed, and Cochrane) were searched for relevant literature on 29 November 2021, supplemented with gray literature searches.

QALYs and ambulatory status: societal preferences for healthcare decision making.

Background: This research aimed to review the theoretical and methodological aspects of the quality-adjusted life year (QALY) which give rise to potential for bias against certain patient populations, including those with problems with walking or an inability to walk (ambulatory disabilities), when health technology assessment decisions rely on QALY gain to show cost-effectiveness. Societal preferences for treating ambulatory versus non-ambulatory patients were also investigated.

Methods: We reviewed published literature to identify information on theoretical underpinnings of the QALY, measurement of utilities for QALY assessment, and empirical evidence of societal preferences for the treatment of ambulatory and non-ambulatory patients.

Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity.

The androgen receptor (AR) is the main driver of prostate cancer (PC) development and progression, and the primary therapeutic target in PC. To date, two functional ubiquitination sites have been identified on AR, both located in its C-terminal ligand binding domain (LBD). Recent reports highlight the emergence of AR splice variants lacking the LBD that can arise during disease progression and contribute to castrate resistance.

Progesterone receptor (PR) variants exist in breast cancer cells characterised as PR negative.

Progesterone receptor (PR) expression is measured in breast cancer by immunohistochemistry using N-terminally targeted antibodies and serves as a biomarker for endocrine therapeutic decisions. Extensive PR alternative splicing has been reported which may generate truncated PR variant proteins which are not detected by current breast cancer screening or may alter the function of proteins detected in screening. However, the existence of such truncated PR variants remains controversial.

Contribution of Toll-like receptor activation to lung damage after donor brain death.

Introduction: Donor brain death is the first injurious event that can produce inflammatory dysfunction after pulmonary transplantation. This study was designed to determine whether stimulation of the toll-like receptor (TLR) system contributes to the changes produced by brain death.

Materials And Methods: Rats were repeatedly treated with specific agonists for TLR4 or TLR2/6 to desensitize these receptors.

Norepinephrine and arginine vasopressin increase hepatic but not renal inflammatory activation during hemodynamic resuscitation in a rodent model of brain-dead donors.

Objectives: Hypotension that occurs after brain death causes a deterioration in organ function, which in turn restricts the number of organs that can be retrieved and leads to graft dysfunction. The correction of hypotension by the administration of norepinephrine increases the number of organs suitable for retrieval but is associated with cardiac allograft failure. Arginine vasopressin is relatively less cardiotoxic; however, the effect of that drug on intra-abdominal organs is unknown.

Alternative splicing and the progesterone receptor in breast cancer.

Progesterone receptor status is a marker for hormone responsiveness and disease prognosis in breast cancer. Progesterone receptor negative tumours have generally been shown to have a poorer prognosis than progesterone receptor positive tumours. The observed loss of progesterone receptor could be through a range of mechanisms, including the generation of alternatively spliced progesterone receptor variants that are not detectable by current screening methods.

Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor.

Background: The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart.

Characterization of cellular retinoid-binding proteins in human myometrium during pregnancy.

Many complementary or competing signalling pathways bear an influence on the myometrium at any one time, and because the retinoic acid signalling pathway influences differentiation of a wide array of human tissues, this may be one of the determinants of myometrial differentiation during pregnancy. We have explored the novel hypothesis that the retinoids may act as important regulators in controlling the differentiated state of the human myometrium during pregnancy by characterizing the expression profiles for cellular retinoid-binding proteins CRBPI, CRABPI and CRABPII in non-pregnant, pregnant (non-labouring) and labouring human myometrium taken from the functionally distinct upper and lower uterine segments. In addition, we have investigated the effect of all-trans retinoic acid (ATRA) on the expression of several retinoic acid response genes including cyclooxygenase-2 (COX-2) and connexin-43 (Cx-43).