Lung transplantation in cystic fibrosis normalizes essential fatty acid profiles

BackgroundCystic fibrosis (CF) can be a devastating disease. Disorders in essential fatty acid state are increasingly reported and various supplementation trials have been performed in an attempt to improve outcomes. However, the mechanisms leading to these disturbances remain elusive.We wanted to investigate the role of the diseased CF lung on fatty acid profiles.MethodsWe compared fatty acid profiles in patients with CF after lung transplantation (n = 11) to age-matched healthy controls and homozygous F508del patients (n = 22 each).ResultsCompared to healthy controls, in patients with CF, there are decreased levels of docosahexaenoic, linoleic and arachidonic acid and increased levels of mead acid. In patients that underwent a lung transplantation, levels of docosahexaenoic, linoleic and arachidonic acid were normal. Mead acid did not decrease significantly.ConclusionsThe diseased CFTR deficient lung is a major determinant in the disturbed fatty acid profile in CF.     

A dual-labeled Annexin A5 is not suited for SPECT imaging of brain cell death in experimental murine stroke

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (AnxA5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled AnxA5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding AnxA5 or the nonfunctional AnxA5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled AnxA5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled AnxA5 appears to be unsuited for visualizing death of brain cells in this MCAO model.     

Dutch guidelines for physiotherapy in patients with stress urinary incontinence: an update

Introduction and hypothesis

Stress urinary incontinence (SUI) is the most common form of incontinence impacting on quality of life (QOL) and is associated with high financial, social, and emotional costs. The purpose of this study was to provide an update existing Dutch evidence-based clinical practice guidelines (CPGs) for physiotherapy management of patients with stress urinary incontinence (SUI) in order to support physiotherapists in decision making and improving efficacy and uniformity of care.

Materials and methods

A computerized literature search of relevant databases was performed to search for information regarding etiology, prognosis, and physiotherapy assessment and management in patients with SUI. Where no evidence was available, recommendations were based on consensus. Clinical application of CPGs and feasibility were reviewed. The diagnostic process consists of systematic history taking and physical examination supported by reliable and valid assessment tools to determine physiological potential for recovery. Therapy is related to different problem categories. SUI treatment is generally based on pelvic floor muscle exercises combined with patient education and counseling. An important strategy is to reduce prevalent SUI by reducing influencing risk factors.

Results

Scientific evidence supporting assessment and management of SUI is strong.

Conclusions

The CPGs reflect the current state of knowledge of effective and tailor-made intervention in SUI patients.     

Protein Quality in Perspective: A Review of Protein Quality Metrics and Their Applications

For design of healthy and sustainable diets and food systems, it is important to consider not only the quantity but also the quality of nutrients. This is particularly important for proteins, given the large variability in amino acid composition and digestibility between dietary proteins. This article reviews measurements and metrics in relation to protein quality, but also their application. Protein quality methods based on concentrations and digestibility of individual amino acids are preferred, because they do not only allow ranking of proteins, but also assessment of complementarity of protein sources, although this should be considered only at a meal level and not a diet level. Measurements based on ileal digestibility are preferred over those on faecal digestibility to overcome the risk of overestimation of protein quality. Integration of protein quality on a dietary level should also be done based on measurements on an individual amino acid basis. Effects of processing, which is applied to all foods, should be considered as it can also affect protein quality through effects on digestibility and amino acid modification. Overall, protein quality data are crucial for integration into healthy and sustainable diets, but care is needed in data selection, interpretation and integration.     

Psoriasis risk genes of the late cornified envelope-3 group are distinctly expressed compared with genes of other LCE groups

Deletion of the late cornified envelope (LCE) genes LCE3B and LCE3C has recently been identified as a risk factor for psoriasis. Expression of 16 LCE genes of LCE groups 1, 2, 3, 5, and 6 was examined in vivo and in vitro. Quantitative PCR demonstrated that moderate to high LCE expression was largely confined to skin and a few oropharyngeal tissues. Genes of the LCE3 group demonstrated increased expression in lesional psoriatic epidermis and were induced after superficial injury of normal skin, whereas expression of members of other LCE groups was down-regulated under these conditions. Immunohistochemistry and immunoelectron microscopy demonstrated that LCE2 protein expression was restricted to the uppermost granular layer and the stratum corneum. Stimulation of in vitro reconstructed skin by several psoriasis-associated cytokines resulted in induction of LCE3 members. The data suggest that LCE proteins of groups 1, 2, 5, and 6 are involved in normal skin barrier function, whereas LCE3 genes encode proteins involved in barrier repair after injury or inflammation. These findings may provide clues to the mechanistic role of LCE3B/C deletion in psoriasis.     

Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.