Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P,0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albuminto-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.

Dengue fever is the most important arthropod-borne viral infection worldwide. Secondary prevention to reduce mortality through improved clinical case management has substantially lowered the mortality rate for severe dengue during the past two decades. Gallbladder wall thickening (GBWT) is a nonspecific finding often associated with more severe cases of dengue infection. This study had the aim to describe the ultrasonographic findings in hospitalized patients with dengue infection from Manaus (in the Western Brazilian Amazon) and to correlate the GBWT with dengue severity, symptoms and laboratorial analysis. Patients from 13–84 years admitted to the emergency department at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) were enrolled in this study. Patients’ selection occurred during the most recent and huge dengue outbreak within the first semester of 2011. All enrolled subjects were systematically tested in order to rule out other possible etiologies for gallbladder inflammation. Abdominal ultrasound was performed by a single physician through bedside portable equipment and all other clinical and laboratorial information were retrieved from patients’ electronic files. 54 subjects were considered for analysis, with confirmed dengue infection by NS1 and/or RT-PCR positivity. From all enrolled patients, 50 (42.4%) presented GBWT. GBWT was significantly and independently related to: age under 31 years, pregnancy, presence of bleeding, presence of any cavitary effusion, DHF classification and severe dengue classifications. During dengue outbreaks, the GBWT identification through a non-invasive and bedside procedure is a confident marker for prompt recognition of potential severe cases.

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This chapter identifies the goals of the current nationwide initiative to eliminate new HIV infections in the US and describes the pillars upon which the initiative was designed to achieve these goals. These goals include reducing the number of new infections by 75% by 2025 and 90% by 2030 by increasing the diagnosis, treatment, and prevention of HIV infection and rapid response to new clusters of HIV transmission.

Quantitative real‐time PCR (qPCR) studies can be used to investigate altered gene expression in animals exposed to varying environmental conditions, but an accurate analysis requires data normalization with stably expressed internal reference genes. We evaluated the relative stability of five reference genes commonly used in qPCR studies; expression profiles in cardiac muscle were determined after acclimation of goldfish (Carassius auratus) to moderately hypoxic conditions (2.6 mg O2/l) for seven days at 22°C. Transcription levels were quantified for β‐actin (ACTB), ubiquitin (UBI), acidic ribosomal protein (ARP), elongation factor (EF‐1α) and major histocompatibility complex (MHC1); primers for each were designed using previously sequenced genes from goldfish and zebrafish (Danio rerio). Stability of gene expression in acclimated vs. non‐acclimated fish was greatest for ACTB and ARP, while EF‐1α proved unsuitable as a reference, showing a consistent downregulation. Statistical analysis suggested that the combined use of ACTB, ARP and UBI as reference genes would allow a robust interpretation of qPCR data after acclimation to chronic hypoxia. The identification of hypoxia‐stable housekeeping genes in goldfish heart will aid future studies of the molecular mechanisms underlying hypoxia‐ and anoxia‐tolerance in this species. (Supported by the HHMI and the Brachman Hoffman Fund)