B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling.

Breast cancer mortality results from incurable recurrences thought to be seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling RTC survival is therefore essential for improving patient outcomes. Here, we derive a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant therapy in patients and is enriched for extracellular matrix-related pathways.

A missense mutation in associated with defective spermatogenesis and male infertility.

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.

PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies.

Background: Breast cancer mortality is principally due to recurrent disease that becomes resistant to therapy. We recently identified copy number (CN) gain of the putative membrane progesterone receptor PAQR8 as one of four focal CN alterations that preferentially occurred in recurrent metastatic tumors compared to primary tumors in breast cancer patients. Whether PAQR8 plays a functional role in cancer is unknown.

A Founder Mutation in Presents with Tubular Proteinuria and Deafness.

Background: The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis.

Cellular dormancy in minimal residual disease following targeted therapy.

Background: Breast cancer mortality is principally due to tumor recurrence, which can occur following extended periods of clinical remission that may last decades. While clinical latency has been postulated to reflect the ability of residual tumor cells to persist in a dormant state, this hypothesis remains unproven since little is known about the biology of these cells. Consequently, defining the properties of residual tumor cells is an essential goal with important clinical implications for preventing recurrence and improving cancer outcomes.

Validation of the Rainbow Model of Integrated Care Measurement Tools (RMIC-MTs) in renal care for patient and care providers.

Introduction: Integrated service delivery is considered to be an essential condition for improving the management and health outcomes of people with chronic kidney disease (CKD). However, research on the assessment of integrated care by patients and care providers is hindered by the absence of brief, reliable, and valid measurement tools.

Objective: The aim of this study was to develop survey instruments for healthcare professionals and patients based on the Rainbow Model of Integrated Care (RMIC), and to evaluate their psychometric properties.

Impact of obesity on breast cancer recurrence and minimal residual disease.

Background: Obesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.

For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure.

Person-Centered Integrated Care for Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background And Objectives: The effectiveness of person-centered integrated care strategies for CKD is uncertain. We conducted a systematic review and meta-analysis of randomized, controlled trials to assess the effect of person-centered integrated care for CKD.

Design, Setting, Participants, & Measurements: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to April of 2016), and selected randomized, controlled trials of person-centered integrated care interventions with a minimum follow-up of 3 months.

Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse.

TASK-1 potassium channels have been implicated in central and peripheral chemoreception; however, the precise contribution of TASK-1 for the control of respiration is still under debate. Here, we investigated the respiration of unrestrained adult and neonatal TASK-1 knockout mice (TASK-1) using a plethysmographic device. Respiration in adult female TASK-1 mice under control (21% O), hypoxia and hypercapnia was unaffected.

Pathogenesis of Adrenal Aldosterone-Producing Adenomas Carrying Mutations of the Na(+)/K(+)-ATPase.

Aldosterone-producing adenoma (APA) is a major cause of primary aldosteronism, leading to secondary hypertension. Somatic mutations in the gene for the α1 subunit of the Na(+)/K(+)-ATPase were found in about 6% of APAs. APA-related α1 subunit of the Na(+)/K(+)-ATPase mutations lead to a loss of the pump function of the Na(+)/K(+)-ATPase, which is believed to result in membrane depolarization and Ca(2+)-dependent stimulation of aldosterone synthesis in adrenal cells.

Standardizing Falls Reporting: Using Data From Adverse Event Reporting to Drive Quality Improvement.

Objective: To enhance the value of the Pennsylvania Patient Safety Reporting System (PA-PSRS) falls reports by developing a falls reporting program that standardizes falls reporting and provides timely benchmarked falls rates and process measurement reports hospitals can use to identify areas of improvement in their falls program.

Methods: The new PA-PSRS falls reporting program requires adherence to standardized definitions of falls to generate standardized, customizable analytic reports. An advisory committee and statewide survey guided the development of the program, data definitions, system features and functionality, and methods for stratifying reporting criteria.

Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.

Breast cancer mortality is principally due to recurrent tumors that arise from a reservoir of residual tumor cells that survive therapy. Remarkably, breast cancers can recur after extended periods of clinical remission, implying that at least some residual tumor cells pass through a dormant phase prior to relapse. Nevertheless, the mechanisms that contribute to breast cancer recurrence are poorly understood.

Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal cortex and regulates aldosterone secretion.

Elucidation of the molecular mechanisms leading to autonomous aldosterone secretion is a prerequisite to define potential targets and biomarkers in the context of primary aldosteronism. After a genome-wide association study with subjects from the population-based Cooperative Health Research in the Region of Augsburg F4 survey, we observed a highly significant association (P=6.78×10(-11)) between the aldosterone to renin ratio and a locus at 5q32.

Visible light guidance in silica capillaries by antiresonant reflection.

Hollow silica capillaries are examined as optical waveguides evaluating the antiresonant reflecting optical waveguide (ARROW) effect by sequentially reducing the wall thickness through etching and measuring the optical transmission. It is found that the periodicity of the transmission bands is proportional to the wall thickness and that the propagation loss is of the order of a few dB/m.

Pharmacology and pathophysiology of mutated KCNJ5 found in adrenal aldosterone-producing adenomas.

Somatic mutations of the potassium channel KCNJ5 are found in 40% of aldosterone producing adenomas (APAs). APA-related mutations of KCNJ5 lead to a pathological Na(+) permeability and a rise in cytosolic Ca(2+), the latter presumably by depolarizing the membrane and activating voltage-gated Ca(2+) channels. The aim of this study was to further investigate the effects of mutated KCNJ5 channels on intracellular Na(+) and Ca(2+) homeostasis in human adrenocortical NCI-H295R cells.

Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome.

Background: In renal Fanconi's syndrome, dysfunction in proximal tubular cells leads to renal losses of water, electrolytes, and low-molecular-weight nutrients. For most types of isolated Fanconi's syndrome, the genetic cause and underlying defect remain unknown.

Methods: We clinically and genetically characterized members of a five-generation black family with isolated autosomal dominant Fanconi's syndrome.

Dynamics of renal electrolyte excretion in growing mice.

Genetically modified mice represent important models for elucidating renal pathophysiology, but gene deletions frequently cause severe failure to thrive. In such cases, the analysis of the phenotype is often limited to the first weeks of life when renal excretory function undergoes dramatic physiological changes. Here, we investigated the postnatal dynamics of urinary ion excretion in mice.

a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III.

Context: Primary aldosteronism is a heterogeneous group of disorders comprising both sporadic and familial forms. Mutations in the KCNJ5 gene, which encodes the inward rectifier K(+) channel 4 (G protein-activated inward rectifier K(+) channel 4, Kir3.4), cause familial hyperaldosteronism type III (FH-III) and are involved in the pathogenesis of sporadic aldosterone-producing adenomas.

Severe hyperaldosteronism in neonatal Task3 potassium channel knockout mice is associated with activation of the intraadrenal renin-angiotensin system.

Task3 K(+) channels are highly expressed in the adrenal cortex and contribute to the angiotensin II and K(+) sensitivity of aldosterone-producing glomerulosa cells. Adult Task3(-/-) mice display a partially autonomous aldosterone secretion, subclinical hyperaldosteronism, and salt-sensitive hypertension. Here, we investigated the age dependence of the adrenal phenotype of Task3(-/-) mice.

Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models.

This study compared the steady state concentration of lactate in an inducible Her2/nue transgenic breast cancer mouse model and in tumours from the same Her2/neu model grown orthotopically. In vivo lactate was detected by MRS using the Hadamard encoded selective multiple quantum coherence pulse sequence (HadSelMQC) recently developed by our laboratory. A lower lactate signal was observed in the inducible tumours compared to orthotopic tumours in vivo, while ex vivo analysis of perchloric acid extracts revealed similar amounts of this metabolite in both models.

Deletion of cyclooxygenase 2 in mouse mammary epithelial cells delays breast cancer onset through augmentation of type 1 immune responses in tumors.

Inhibition of cyclooxygenase (COX) 2, which is associated with >40% of breast cancers, decreases the risk of tumorigenesis and breast cancer recurrence. To study the role of COX-2 in breast cancer, we engineered mice that lack selectively mammary epithelial cell (MEC) COX-2 (COX-2 KO(MEC)). Compared with wild type (WT), MEC from COX-2 KO(MEC) mice expressed >90% less COX-2 messenger RNA (mRNA) and protein and produced 90% less of the dominant pro-oncogenic COX-2 product, prostaglandin (PG) E(2).

Phase-shifted Bragg microstructured optical fiber gratings utilizing infiltrated ferrofluids.

Results are presented on the efficient spectral manipulation of uniform and chirped Bragg reflectors inscribed in microstructured optical fibers utilizing short lengths of ferrofluids infiltrated in their capillaries. The infiltrated ferrofluidic defects can generate either parasitic reflection notch features in uniform Bragg reflectors of up to 80% visibility and ~0.1 nm spectral shift or tunability of the bandwidth and strength reflection up to 100% when introduced into chirped gratings.

Dynamics of long-period gratings tuned with internal fiber electrodes.

The physics of electrically switched long-period grating in a twin-hole fiber with internal electrodes is studied. Dynamic measurements for the two polarizations show how the grating spectra shift in time due to the mechanical stress and heat transfer in the core and the cladding.

KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function.

Mutations of the KCNJ10 (Kir4.1) K(+) channel underlie autosomal recessive epilepsy, ataxia, sensorineural deafness, and (a salt-wasting) renal tubulopathy (EAST) syndrome. We investigated the localization of KCNJ10 and the homologous KCNJ16 in kidney and the functional consequences of KCNJ10 mutations found in our patients with EAST syndrome.