Enhancing quantitative approaches for assessing community resilience.

Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience.

Targeting ovarian cancer and endothelium with an allosteric PTP4A3 phosphatase inhibitor.

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways.

Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis.

Background: Elevated lipoprotein(a) (Lp[a]) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease (CAD) in patients admitted to the coronary care unit (CCU) remain to be defined.

Hypothesis: Elevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk.

A Comparative Analysis of Phenotypic Predictors of Mutations in Familial Hypercholesterolemia.

Context: The gold standard for diagnosing familial hypercholesterolemia (FH) is identification of a causative pathogenic mutation. However, genetic testing is expensive and not widely available.

Objective: To compare the validity of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), Make Early Diagnosis to Prevent Early Deaths (MEDPED), and American Heart Association (AHA) criteria in predicting an FH-causing mutation.

The role of patient registries for rare genetic lipid disorders.

Purpose Of Review: We review the role, utility and current status of patient registries for rare genetic lipid disorders.

Recent Findings: The creation and maintenance of rare genetic lipid disorder patient registries is critical for disease monitoring, improving clinical best practice, facilitating research and enabling the development of novel therapeutics. An open-source disease registry platform, termed the Rare Disease Registry Framework, has been developed, optimized and deployed for homozygous familial hypercholesterolemia.

HIV Replication and Latency in a Humanized NSG Mouse Model during Suppressive Oral Combinational Antiretroviral Therapy.

Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy.

HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 20 Cities, United States, 2015.

In the United States, 9% of human immunodeficiency virus (HIV) infections diagnosed in 2015 were attributed to injection drug use (1). In 2015, 79% of diagnoses of HIV infection among persons who inject drugs occurred in urban areas (2). To monitor the prevalence of HIV infection and associated behaviors among persons who inject drugs, CDC's National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing in selected metropolitan statistical areas (MSAs) (3).

A favorable cardiometabolic profile is associated with the G allele of the genetic variant rs5068 in African Americans: The Multi-Ethnic Study of Atherosclerosis (MESA).

In whites, the minor G allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with higher circulating levels of ANP and B-type natriuretic peptide (BNP), lower risk of hypertension, higher high-density lipoprotein (HDL) cholesterol plasma levels, and lower prevalence of obesity and metabolic syndrome. The observed phenotype is consistent with the blood pressure lowering and metabolic properties of ANP and BNP. The cardiovascular and metabolic phenotype associated with rs5068 genotypes in African Americans is undefined.

A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure.

Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic peptide (DNP). Cenderitide was engineered to coactivate the two NP receptors, particulate guanylyl cyclase (pGC)-A and -B. The rationale for its design was to achieve the renal-enhancing and antifibrotic properties of dual receptor activation, but without clinically significant hypotension.

Impact of regulatory variation across human iPSCs and differentiated cells.

Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes.

CRRL269: a novel designer and renal-enhancing pGC-A peptide activator.

The natriuretic peptides (NPs) B-type NP (BNP) and urodilatin (URO) exert renal protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As a potential renal-enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions.

Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the Hedgehog pathway.

Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory.

Towards a needle-free diagnosis of malaria: in vivo identification and classification of red and white blood cells containing haemozoin.

Background: Optical detection of circulating haemozoin has been suggested as a needle free method to diagnose malaria using in vivo microscopy. Haemozoin is generated within infected red blood cells by the malaria parasite, serving as a highly specific, endogenous biomarker of malaria. However, phagocytosis of haemozoin by white blood cells which persist after the infection is resolved presents the potential for false positive diagnosis; therefore, the focus of this work is to identify a feature of the haemozoin signal to discriminate between infected red blood cells and haemozoin-containing white blood cells.

Filiarial chyluria with nephrotic-range proteinuria and associated hypoalbuminaemia and hypogammaglobulinaemia secondary to bilateral lymphorenal fistulae.

A 55-year-old man of Indian descent, presented to the emergency department with a 2-year history of passing 'milky' white urine, associated with dysuria, urinary retention, bilateral flank pain and 15 kg weight loss. He had migrated to Australia from India at the age of 16, with no overseas travel since, and denied having any fevers, rigours or chills. He was found to have chyluria and nephrotic-range proteinuria with marked hypoalbuminaemia and hypogammaglobulinaemia.

Small molecule targeting of PTPs in cancer.

Protein tyrosine phosphatases (PTPs) undeniably have a central role in the development and progression of human cancers. Historically, however, PTPs have not been viewed as privileged drug targets, and progress on identifying potent, selective, and cell-active small molecule PTP inhibitors has suffered accordingly. This situation is rapidly changing, however, due to biochemical advances in the study of PTPs and recent small molecule screening campaigns, which have identified potent and mechanistically diverse lead structures.

Over-Expression of Alpha-Enolase as a Prognostic Biomarker in Patients with Pancreatic Cancer.

Alpha-enolase is an important glycolytic enzyme, and its aberrant expression has been associated with multiple tumor progression. However, few studies investigated the expression of alpha-enolase and its clinical significance in pancreatic cancer (PC). To evaluate alpha-enolase level in PC tissues by immunohistochemical (IHC) analysis, and investigate the association of alpha-enolase expression with clinicopathologic features.

Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.

Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The primary cilium is a microtubule-based organelle that is essential for Hedgehog (Hh) signaling, but it has also been implicated in the regulation of other signaling pathways. Here, we show that the optic primordium is ciliated during early eye development and that ciliogenesis is essential for proper patterning and morphogenesis of the mouse eye.

Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis).

Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown.

Medication Regimen Complexity and Low Adherence in Older Community-Dwelling Adults With Substantiated Self-Neglect.

Objective: Determine whether medication regimen complexity predicts medication adherence levels in a sample of community-dwelling adults 65 years and older with Adult Protective Services-substantiated self-neglect.

Methods: A cross-sectional analysis of baseline data ( N = 31 participants) from a pilot intervention to increase medication adherence among the target group was performed. The Medication Regimen Complexity Index (MRCI) and the 8-item Morisky Medication Adherence Scale (MMAS-8)™ were the primary independent and dependent measures, respectively.

Atrial Natriuretic Peptide - Old But New Therapeutic in Cardiovascular Diseases.

With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF).

Experimental cardiac radiation exposure induces ventricular diastolic dysfunction with preserved ejection fraction.

Breast cancer radiotherapy increases the risk of heart failure with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radioresistant, but radiation specifically affects coronary microvascular endothelial cells, with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized.