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Mitochondrial defects are implicated in multiple diseases and aging. Exercise training is an accessible, inexpensive therapeutic intervention that can improve mitochondrial bioenergetics and quality of life. By combining multiple omics techniques with biochemical and in silico normalisation, we removed the bias arising from the training-induced increase in mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritised mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the overall increase in mitochondrial content. Our findings suggest enhancing electron flow to oxidative phosphorylation (OXPHOS) is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and do not support the hypothesis that training-induced supercomplex formation enhances mitochondrial bioenergetics. Our study provides an analytical approach allowing unbiased and in-depth investigations of training-induced mitochondrial adaptations, challenging our current understanding, and calling for careful reinterpretation of previous findings., (© 2021. The Author(s).)

Background: The aims of the present study were to investigate the impact of three whole blood donations on endurance capacity and hematological parameters and to determine the duration to fully recover initial endurance capacity and hematological parameters after each donation., Methods: Twenty-four moderately trained subjects were randomly divided in a donation (n = 16) and a placebo (n = 8) group. Each of the three donations was interspersed by 3 months, and the recovery of endurance capacity and hematological parameters was monitored up to 1 month after donation., Results: Maximal power output, peak oxygen consumption, and hemoglobin mass decreased (p < 0.001) up to 4 weeks after a single blood donation with a maximal decrease of 4, 10, and 7%, respectively. Hematocrit, hemoglobin concentration, ferritin, and red blood cell count (RBC), all key hematological parameters for oxygen transport, were lowered by a single donation (p < 0.001) and cumulatively further affected by the repetition of the donations (p < 0.001). The maximal decrease after a blood donation was 11% for hematocrit, 10% for hemoglobin concentration, 50% for ferritin, and 12% for RBC (p < 0.001). Maximal power output cumulatively increased in the placebo group as the maximal exercise tests were repeated (p < 0.001), which indicates positive training adaptations. This increase in maximal power output over the whole duration of the study was not observed in the donation group., Conclusions: Maximal, but not submaximal, endurance capacity was altered after blood donation in moderately trained people and the expected increase in capacity after multiple maximal exercise tests was not present when repeating whole blood donations.

Background: While in general practice chronic non-specific abdominal complaints are common, there is insufficient data on the clinical course and the management of these complaints. Aim of this study was to present a primary care based profile of these chronic complaints including health care involvement, health status and clinical course., Methods: Thirty general practitioners (GPs) and patients from their practices participated in a prospective follow-up study. All patients and GPs were asked to complete questionnaires at baseline and at 6, 12 and 18 months of follow-up. The GPs provided information on diagnostic and therapeutic management and on referral concerning 619 patients with chronic non-specific abdominal complaints, while 291 patients provided information about health status and clinical course of the complaints., Results: When asked after 18 months of follow-up, 51,7% of the patients reported an equal or worsened severity of complaints. General health perception was impaired and patients had high scores on SCL-anxiety and SCL-depression scales. Diagnostic tests other than physical examination and laboratory tests were not frequently used. Medication was the most frequent type of treatment. The persistence of chronic non-specific abdominal complaints was quite stable., Conclusion: Once non-specific chronic abdominal complaints have become labelled as chronic by the attending physician, little improvement can be expected. The impact on patients' physiological and psychological well-being is large. GPs use a variety of diagnostic and therapeutic strategies. Research into the evidence base of currently applied management strategies is recommended.

Background: While chronic non-specific abdominal complaints are common in general practice, data on patients' perspective and management of these complaints are lacking. Knowledge of these data is important for the development of guidelines for management and assessment of the burden of chronic non-specific abdominal complaints on society., Aim: To draw a comprehensive picture of chronic non-specific abdominal complaints in general practice, including volume, patients' perspective, and health care involvement., Method: In a retrospective study, 644 patients were selected in 16 general practices. Patients and general practitioners (GPs) received a questionnaire regarding the nature of complaints and health care management during the previous 12 months., Results: Overall, 619 questionnaires were returned and 291 patients participated. Of the study population, 15% of patients were diagnosed as suffering from non-ulcer dyspepsia, 39% from irritable bowel syndrome, and 45% from other abdominal complaints. Over 50% of patients suffered from chronic non-specific abdominal complaints on a daily or weekly basis. In these patients, general health perception is impaired and above norm scores on SCL-anxiety and SCL-depression scales were recorded. Only 4% of patients showed complete resolution of complaints during the previous 12 months. Fifty-two per cent of patients consulted their GP for abdominal complaints. Diagnostic modalities were used frequently. Medication was prescribed in 83% of patients with abdominal complaints. Twenty per cent of patients were referred to secondary or tertiary care. There was a considerable inter-doctor variation in the management of chronic non-specific abdominal complaints., Conclusion: Once non-specific abdominal complaints have become chronic they are mainly managed by the GP. The impact on patients' physiological and psychological well being is large. Diagnostic and therapeutic modalities are frequently used. Given the considerable inter-doctor variation, research into the evidence base of management strategies is recommended.

A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization techniques was used to map YACs, cosmids and DNA markers from the Xp11.2 region relative to the X chromosome breakpoint of the renal cell carcinoma-associated t(X;1)(p11;q21). The position of the breakpoint could be determined as follows: Xcen-OATL2-DXS146-DXS255-SYP-t(X;1)-TFE 3-OATL1-Xpter. Fluorescence in situ hybridization experiments using TFE3-containing YACs and cosmids revealed split signals indicating that the corresponding DNA inserts span the breakpoint region. Subsequent Southern blot analysis showed that a 2.3-kb EcoRI fragment which is present in all TFE3 cosmids identified, hybridizes to aberrant restriction fragments in three independent t(X;1)-positive renal cell carcinoma DNAs. The breakpoints in these tumors are not the same, but map within a region of approximately 6.5 kb. Through preparative gel electrophoresis an (X;1) chimaeric 4.4-kb EcoRI fragment could be isolated which encompasses the breakpoint region present on der(X). Preliminary characterization of this fragment revealed the presence of a 150-bp region with a strong homology to the 5' end of the mouse TFE3 cDNA in the X-chromosome part, and a 48-bp segment in the chromosome 1-derived part identical to the 5' end of a known EST (accession number R93849). These observations suggest that a fusion gene is formed between the two corresponding genes in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.

The diagnosis of peripheral ischemic diseases is a challenge to the vascular specialist, since discrimination of the different entities on clinical grounds is not always clear. Capillary microscopy is a noninvasive diagnostic technique that can visualize in particular the morphology and perfusion of the digital capillaries. The authors investigated all 522 patients who were referred to the vascular laboratory over a six-year period, in an attempt to obtain more certainty about the diagnosis of their acral ischemic complaints. Patients with clinically manifest Raynaud's phenomenon and control subjects were compared to obtain differentiation criteria. Thus, capillary microscopy scored a sensitivity of 67%, a specificity of 84%, and an accuracy of 81% to detect Raynaud's phenomenon. A disturbed capillary morphology was virtually pathognomonic in Raynaud's disease secondary to systemic disorders (specificity 100%); the accuracy was but 74%. In 69% of the patients with clinically atypical acral ischemia, capillary microscopy yielded a diagnosis. Digital blood pressure measurements, however, appeared of no use in the diagnosis of Raynaud's phenomenon. Hence, capillary microscopy appears to be a useful aid in the diagnosis of acral ischemic syndromes.

Recently, a specific chromosome abnormality, t(X;1)(p11;q21), was described for a subgroup of human papillary renal cell carcinomas. The translocation breakpoint in Xp11 is located in the same region as that in t(X;18)(p11;q11)-positive synovial sarcoma. We used fluorescence in situ hybridization (FISH) and somatic cell hybridization techniques to demonstrate 1) that the Xp11 translocation breakpoint in papillary renal cell carcinoma differs from that observed in synovial sarcoma and has a more proximal location, and 2) that an ornithine aminotransferase (OAT)L2 containing yeast artificial chromosome (YAC) spans the X;1 translocation. This YAC provides an ideal starting point from which the breakpoint itself and the gene(s) involved can be isolated and characterized.

A series of thirteen different DNA markers was mapped relative to papillary renal cell carcinoma- and synovial sarcoma-associated translocation breakpoints in Xp11.2 using a panel of tumor-derived somatic cell hybrids in conjunction with Southern blot analysis. Our results indicate that the two translocation breakpoints differ from each other and that the chromosomal break in t(X;1)-positive papillary renal cell carcinoma is located between the markers PFC-TIMP-OATL1-SYP-TFE3 and DXS226-DXS146-DXS255-OATL2-DXS14. In addition, our current breakpoint analysis has resulted in a revision of the regional localization of the proximal Xp marker DXS226.