Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Oral health related quality of life and its association with sociodemographic and clinical findings in 3 northern outreach clinics.

OBJECTIVE: Aspects of oral health related quality of life (OHQOL) are attracting increased attention in dentistry. Knowledge in this field is limited, especially in terms of significant indicators and predictors of impaired OHQOL. The aim of this cross-sectional study was to examine the influence of various sociodemographic and clinical variables on OHQOL in the setting of outreach clinics in northern Alberta, Canada. METHODS: OHQOL was measured with the 49-item Oral Health Impact Profile questionnaire (OHIP-49), administered to adult patients attending 3 dental outreach clinics managed by the University of Alberta. Sociodemographic and clinical data were also collected. Data were analyzed using descriptive and multivariable methods. RESULTS: The OHIP-49 scores were comparatively low for a patient sample. After multivariable stepwise logistic regression analysis, only gender, missing anterior teeth and need for endodontic treatment remained as significant variables in the final model for impaired OHQOL. Missing anterior teeth (regardless of replacement) had the strongest effect. Subjects with this feature had an approximately 21-fold greater risk of impaired OHQOL relative to those who retained all of their anterior teeth. CONCLUSIONS: The clientele of these outreach clinics was generally young but had high treatment needs. OHQOL results can be useful in considering treatment strategies in similar rural environments, but the complexity of this indicator necessitates an individual patient-centred approach in clinical decision-making.

A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase.

The small and large subunits of molybdopterin (MPT) synthase (MOCS2A and MOCS2B), are both encoded by the MOCS2 gene in overlapping and shifted open reading frames (ORFs), which is a highly unusual structure for eukaryotes. Theoretical analysis of genomic sequences suggested that the expression of these overlapping ORFs is facilitated by the use of alternate first exons leading to alternative transcripts. Here, we confirm the existence of these overlapping transcripts experimentally. Further, we identified a deletion in a molybdenum cofactor deficient patient, which removes the start codon for the small subunit (MOCS2A). We observed undisturbed production of both transcripts, while Western blot analysis demonstrated that MOCS2B, the large subunit, is unstable in the absence of MOCS2A. This reveals new insights into the expression of this evolutionary ancient anabolic system.