Work participation, social roles, and empowerment of Q-fever fatigue syndrome patients ≥10 years after infection.

OBJECTIVE: To determine work participation, social roles, and empowerment of QFS patients ≥10-year after infection. METHODS: QFS patients ≥10-year after acute infection, who were of working age, participated in a cross-sectional survey study. Work participation, fulfilment of social roles, and empowerment outcomes were studied for the total population, as well as for subgroups based on employment type and current work status. Associations between empowerment, work and social roles were examined. RESULTS: 291 participants were included. Of the 250 participants who had paid work before Q-fever, 80.4% stopped working or worked less hours due to QFS. For each social role, more than half of the participants (56.6-87.8%) spent less time on the role compared to before Q-fever. The median empowerment score was 41.0 (IQR: 37.0-44.0) out of 60. A higher empowerment score was significantly associated with lower odds of performing all social roles less due to QFS (OR = 0.871-0.933; p<0.001-0.026), except for parenting and informal care provision (p = 0.070-0.460). No associations were found between empowerment and current work status. CONCLUSION: Work participation and fulfilment of social roles is generally low in QFS patients. Many of the participants stopped working or are working less hours due to QFS, and most spent less time on social roles compared to before Q-fever. Minor variation was seen in total empowerment scores of participants; however, these slight differences were associated with the fulfilment of social roles, but not work participation. This new insight should be further explored in future studies.

Sacral neuromodulation versus personalized conservative treatment in patients with idiopathic slow-transit constipation: study protocol of the No.2-trial, a multicenter open-label randomized controlled trial and cost-effectiveness analysis.

PURPOSE: The evidence regarding the (cost-)effectiveness of sacral neuromodulation (SNM) in patients with therapy-resistant idiopathic slow-transit constipation is of suboptimal quality. The Dutch Ministry of Health, Welfare and Sports has granted conditional reimbursement for SNM treatment. The objective is to assess the effectiveness, cost-effectiveness, and budget impact of SNM compared to personalized conservative treatment (PCT) in patients with idiopathic slow-transit constipation refractory to conservative treatment. METHODS: This study is an open-label, multicenter randomized controlled trial. Patients aged 14 to 80 with slow-transit constipation, a defecation frequency (DF) < 3 per week and meeting at least one other Rome-IV criterion, are eligible. Patients with obstructed outlet, irritable bowel syndrome, bowel pathology, or rectal prolapse are excluded. Patients are randomized to SNM or PCT. The primary outcome is success at 6 months (DF ≥ 3 a week), requiring a sample size of 64 (α = 0.05, ß = 0.80, 30% difference in success). Secondary outcomes are straining, sense of incomplete evacuation, constipation severity, fatigue, constipation specific and generic quality of life, and costs at 6 months. Long-term costs and effectiveness will be estimated by a decision analytic model. The time frame is 57 months, starting October 2016. SNM treatment costs are funded by the Dutch conditional reimbursement program, research costs by Medtronic. CONCLUSIONS: The results of this trial will be used to make a final decision regarding reimbursement of SNM from the Dutch Health Care Package in this patient group. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov , identifier NCT02961582, on 12 October 2016.

Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate.

BACKGROUND AND PURPOSE: Recently, two phase-II trials demonstrated improved renal function in critically ill patients with sepsis-associated acute kidney injury treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active effect on renal protection of alkaline phosphatase. EXPERIMENTAL APPROACH: The effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal injury was studied in Sprague-Dawley rats. Renal function was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. The mechanism of action of recAP was further investigated in vitro using conditionally immortalized human proximal tubular epithelial cells (ciPTEC). KEY RESULTS: In vivo, LPS administration significantly prolonged FITC-sinistrin half-life and increased fractional urea excretion, which was prevented by recAP co-administration. Moreover, recAP prevented LPS-induced increase in proximal tubule injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS-induced production of TNF-α, IL-6 and IL-8 was significantly attenuated by recAP. This effect was linked to dephosphorylation, as enzymatically inactive recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection resulted in increased adenosine levels through dephosphorylation of LPS-induced extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM-241385 did not diminish the effects of recAP. CONCLUSIONS AND IMPLICATIONS: These results indicate that the ability of recAP to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect.

The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney, where the transporter is abundant. In bcrp/abcg2((-/-)) mice, the expression of two sterol transporter genes, abcg5 and abcg8, was strongly increased in the kidney, perhaps as a compensatory mechanism to upregulate efflux. We found using immunohistochemical analysis clear localization of BCRP/ABCG2 to the proximal tubule brush border membrane of the human kidney comparable to that of other ABC transporters such as P-glycoprotein/ABCB1, MRP2/ABCC2, and MRP4/ABCC4. Hoechst 33342 dye efflux from primary human proximal tubule cells was significantly reduced by the BCRP/ABCG2 inhibitors fumitremorgin C and nelfinavir. Our study shows that in addition to other apical ABC transporters, BCRP/ABCG2 may be important in renal drug excretion.

[Suckling calves with symptoms of swayback]. / Het beeld van swayback bij zoogkalveren.

Within a 1-year period, three calves from the same herd developed ataxia of the hind limbs and urinary incontinence at about 6 months of age. Signs progressed and the calves were slaughtered 1-8 months after the onset of signs. The calves belonged to a suckling beef herd of 35 cattle. Blood samples from 11 cattle of different ages were collected and glutathione peroxidase and copper levels were measured. Glutathione peroxidase levels were below the normal range in all cattle and copper levels were below the normal range in 7 of ll cattle. Pathological examination of an affected calf revealed a Wallerian type of degeneration of myelinated nerve fibres in the lateral and ventral spinal cord tracts. In addition, the hepatic copper content was very low. Copper deficiency is a well-known cause of swayback in young sheep and goats. To our knowledge, this is the first report of a possible association between a swayback-like syndrome and copper deficiency in calves.