Glycolytic lactate in diabetic kidney disease.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

The Promotion and Development of One Health at Swiss TPH and Its Greater Potential.

One Health, an integrated health concept, is now an integral part of health research and development. One Health overlaps with other integrated approaches to health such as EcoHealth or Planetary Health, which not only consider the patient or population groups but include them in the social-ecological context. One Health has gained the widest foothold politically, institutionally, and in operational implementation. Increasingly, One Health is becoming part of reporting under the International Health Legislation (IHR 2005). The Swiss Tropical and Public Health Institute (Swiss TPH) has played a part in these developments with one of the first mentions of One Health in the biomedical literature. Here, we summarise the history of ideas and processes that led to the development of One Health research and development at the Swiss TPH, clarify its theoretical and methodological foundations, and explore its larger societal potential as an integrated approach to thinking. The history of ideas and processes leading to the development of One Health research at the Swiss TPH were inspired by far-sighted and open ideas of the directors and heads of departments, without exerting too much influence. They followed the progressing work and supported it with further ideas. These in turn were taken up and further developed by a growing number of individual scientists. These ideas were related to other strands of knowledge from economics, molecular biology, anthropology, sociology, theology, and linguistics. We endeavour to relate Western biomedical forms of knowledge generation with other forms, such as Mayan medicine. One Health, in its present form, has been influenced by African mobile pastoralists' integrated thinking that have been taken up into Western epistemologies. The intercultural nature of global and regional One Health approaches will inevitably undergo further scrutiny of successful ways fostering inter-epistemic interaction. Now theoretically well grounded, the One Health approach of seeking benefits for all through better and more equitable cooperation can clearly be applied to engagement in solving major societal problems such as social inequality, animal protection and welfare, environmental protection, climate change mitigation, biodiversity conservation, and conflict transformation.

Crescentic Glomerulonephritis and Membranous Nephropathy: A Rare Overlap.

Background: Membranous nephropathy (MN) is a disease that affects the basement membrane of the glomeruli of the kidney resulting in proteinuria. The concurrent incidence of vasculitic glomerulonephritis and MN in the same patient is unusual. Herein, we report a case with this unusual combination. Case: Our patient is a 53-year-old Hispanic male with a medical history of tobacco use, type 2 diabetes mellitus, and hypertension who presented with hematuria and was found to have nephrotic range proteinuria and renal impairment. Blood workup revealed positive ANCA serology, which led to a renal biopsy that showed crescentic vasculitis in addition to membranous nephropathy. The patient was started on intermittent hemodialysis (HD) and treated initially with intravenous (IV) pulse steroids; subsequently, oral prednisolone and IV cyclophosphamide were initiated. The patient remained HD dependent at the time of discharge with the resolution of hematuria. A follow-up with an outpatient nephrology clinic was arranged. Conclusion: Membranous nephropathy complicated by crescentic glomerulonephritis has a more aggressive clinical course and decline in renal function compared to MN alone which can lead to initiating renal replacement therapy. However, immunosuppressive drugs can result in significant improvement of renal function if started early enough.

Integrated community based human and animal syndromic surveillance in Adadle district of the Somali region of Ethiopia.

The economy of Ethiopia largely depends on agriculture and roughly 80% of the households have direct contact with domestic animals which make the community vulnerable to zoonotic diseases, especially in pastoral areas like the Somali Regional State (SRS) of Ethiopia. However, in addition to low reporting rates, especially in livestock, there is also lack of coordination between public health and animal health surveillance and there is no linkage between public health system and animal health system and mechanism or structure for sharing information on zoonotic diseases in SRS. In view of these challenges, a small scale study was conducted to evaluate the feasibility of mobile communication in the early detection of human and animal syndromes in remote pastoral areas including where there are no human and animal health facilities by engaging local communities in the diseases surveillance. METHOD: A small scale study, testing a community based human and animal syndromic surveillance was conducted from August 2017 to February 2018 in 20 villages in four Kebeles of Adadle district in the SRS with an estimated 1390 households and 112,850 livestock. The selected community leaders were trained on disease surveillance and detection. The communication was done by direct calls. Two dollars per month were provided to the village leaders recruited for the surveillance. RESULTS: A total of 904 and 671 human and animal syndrome cases were reported in seven months of the study period. In addition to syndromes, suspected anthrax, sheep and goat pox (SGP), rabies, salmonellosis and mass abortion outbreaks were reported in animals. In humans, suspected cholera and chicken pox outbreaks were reported. Furthermore, tuberculosis and malaria cases were also confirmed in the study villages. In humans, gastrointestinal tract (GIT) disorder was the most common syndrome observed, which constituted (42.8%) of all syndromes, followed by respiratory disorder (37.8%) and febrile illness (15.5%). In livestock, cattle contributed (40.8%) of all cases of illness, while sheep, goats and camels contributed 24.1%, 18% and 17% of the cases respectively. Responses were organized for emergency treatment and vaccination campaigns against certain suspected disease outbreaks and emergencies such as SGP and cholera. CONCLUSION: This study suggests that engaging and empowering the village local leaders in disease surveillance in pastoral setting areas, including where there are no human and animal health facilities, coupled with mobile technologies (non-smart phone), would improve early detection and response to human and animal health events including zoonotic emergencies, and consequently improve the reporting rate at district, regional and national level. However, the collaboration between sectors (human health and animals health) and the capacity to respond to zoonotic diseases and etiological identification are crucial elements for effective integrated human and animals disease surveillance and response.