Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.

Background: Activation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease-related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fibre contractile function and assess skeletal muscle SMase activity in heart failure patients.

Methods: The effects of SMase on force production and intracellular Ca handling were investigated in single intact human muscle fibres.

Quantitative assessment of morphology and sub-cellular changes in macrophages and trophoblasts during inflammation.

In pregnancy during an inflammatory condition, macrophages present at the feto-maternal junction release an increased amount of nitric oxide (NO) and pro-inflammatory cytokines such as TNF- and INF-γ, which can disturb the trophoblast functions and pregnancy outcome. Measurement of the cellular and sub-cellular morphological modifications associated with inflammatory responses are important in order to quantify the extent of trophoblast dysfunction for clinical implication. With this motivation, we investigated morphological, cellular and sub-cellular changes in externally inflamed RAW264.

[Quality of life the goal of care for patients with ALS].

ALS is characterized by the degeneration of upper and lower motor neurons. In about 70% of patients with ALS the disease has an spinal onset, while about 30% of the patients have a bulbar onset.  Cognitive dysfunction and behavioral changes are seen in about 50% of the patients, and 15% develop frontotemporal dementia.

Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Partially spatially coherent digital holographic microscopy and machine learning for quantitative analysis of human spermatozoa under oxidative stress condition.

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Shared heritability and functional enrichment across six solid cancers.

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r = 0.

The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2-) breast cancer: When might multigene assays be of value?

Background: A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions.

Dendritic cell functional properties in a three-dimensional tissue model of human lung mucosa.

In lung tissue, dendritic cells (DC) are found in close association with the epithelial cell layer, and there is evidence of DC regulation by the epithelium; that epithelial dysfunction leads to overzealous immune cell activation. However, dissecting basic mechanisms of DC interactions with epithelial cells in human tissue is difficult. Here, we describe a method to generate a three-dimensional organotypic model of the human airway mucosa in which we have implanted human DC.

Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.

There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution.

Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome.

Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of approximately 5 ml/kg after 30 min of ventilation.

Pituitary control of lipoprotein and bile acid metabolism in male rats: growth hormone effects are not mediated by prolactin.

Previous studies have established that growth hormone (GH) has many important effects on the regulation of cholesterol and lipoprotein metabolism. However, human GH (hGH) can also bind to prolactin receptors, eliciting prolactin receptor-mediated effects. In this study, we evaluated whether hGH can exert such responses in currently used animal models and whether prolactin affects lipoprotein and/or hepatic cholesterol metabolism.