Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

PARK7 is induced to protect against endotoxic acute kidney injury by suppressing NF-κB

Abstract: Abstract Sepsis is a leading cause of acute kidney injury (AKI), and the pathogenesis of septic AKI remains largely unclear. Parkinson disease protein 7 (PARK7) is a protein of multiple functions that was recently implicated in septic AKI, but the underlying mechanism is unknown. In the present study, we determined the role of PARK7 in septic AKI and further explored the underlying mechanism in lipopolysaccharide (LPS)-induced endotoxic models. PARK7 was induced both in vivo and in vitro following LPS treatment. Compared with wild-type (WT) mice, Park7-deficient mice experienced aggravated kidney tissue damage and dysfunction, and enhanced tubular apoptosis and inflammation following LPS treatment. Consistently, LPS-induced apoptosis and inflammation in renal tubular cells in vitro were exacerbated by Park7 knockdown, whereas they were alleviated by PARK7 overexpression. Mechanistically, silencing Park7 facilitated nuclear translocation and phosphorylation of p65 (a key component of the nuclear factor kappa B [NF-κB] complex) during LPS treatment, whereas PARK7 overexpression partially prevented these changes. Moreover, we detected PARK7 interaction with p65 in the cytoplasm in renal tubular cells, which was enhanced by LPS treatment. Collectively, these findings suggest that PARK7 is induced to protect against septic AKI through suppressing NF-κB signaling.

A continuous cardiac murmur.

Abstract: A 45-year-old woman presents with progressive shortness of breath and a continuous murmur over the entire precordium.

Gut dysbiosis protects against liver injury in autophagy deficient mice by FXR-FGF15 feedback signaling

Abstract: ObjectiveThe gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM and in turn the effect of gut dysbiosis on liver injury. DesignFecal microbiota from mice with liver-specific loss of autophagy-related gene 5 (Atg5), Atg5{Delta}hep mice, were analyzed by 16S sequencing. Antibiotics (ABX) was used to modulate GM in mice. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice over-expressing FGF15 gene, or given a fibroblast growth factor receptor 4 (FGFR4) inhibitor. ResultsThe composition of GM was significantly changed with a notable increase of BA-metabolizing bacteria in Atg5{Delta}hep mice, leading to a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs in the intestine, which markedly activated ileal FXR with an increased expression of FGF15. ABX or cholestyramine treatment exacerbated liver injury and ductular reaction, and decreased FGF15 expression, whereas modulating FGF15 signaling altered liver phenotypes in the autophagy-deficient mice. ConclusionGut dysbiosis can remedy liver injury in Atg5{Delta}hep mice through the FXR-FGF15 signaling. Antibiotics use in the condition of liver injury may have unexpected adverse consequences via the gut-liver axis. SHORT SUMMARYO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIGut microbiota (GM) can be altered during hepatic pathogenesis. C_LIO_LIGM are involved in bile acid (BA) metabolism. C_LIO_LIAutophagy deficiency in the liver disrupts BA homeostasis and causes cholestatic injury. C_LI What are the new findings?O_LIDeficiency of autophagy in the liver causes alteration of GM, which leads to a higher proportion of BA-metabolizing bacteria. C_LIO_LIGM contribute to the activation of ileal farnesoid X receptor (FXR) and a higher expression of fibroblast growth factor 15 (FGF15) in autophagy deficient condition in the liver, which is associated with decreased levels of conjugated BAs and increased levels of unconjugated BAs in the intestine. C_LIO_LIManipulations that lead to GM alteration, intestinal BA signaling, or FGF15 signaling can all modulate the liver phenotype. C_LIO_LIBA and GM together can act as a sensor to liver injury to trigger FGF15-mediated protective mechanism. C_LI How might it impact on clinical practice in the foreseeable future?O_LIThese findings indicate that gut dysbiosis in the scenario of liver disease can be beneficial, suggesting cautions should be exercised in the use of antibiotics during specific liver diseases. C_LIO_LIIf antibiotics need to be used in patients with liver diseases it may be beneficial to enhance the FXR-FGF15 feedback signaling to retain the protective effect of GM. C_LI

Impact of early hypothalamic-pituitary-gonadal axis maturation on prostate cancer: cross-sectional analysis of a Veterans affairs cohort

Abstract: Background It has been hypothesized that earlier onset of puberty, and thus a more prolonged exposure to high androgen levels, increases risk of prostate cancer development. Our objective was to determine whether earlier age of first shave and height, as surrogates of pubertal onset, were associated with risk of prostate cancer diagnosis. Methods A prospectively collected outcomes registry of patients presenting for a prostate biopsy at the Charlie Norwood Veterans Affair Medical Center in Augusta, GA between July 1995 and June 2016 was utilized. The associations between age of first shave and height, each, and risks of a positive prostate biopsy, high grade cancer, and high volume disease were evaluated using univariable and multivariable logistic regression analysis, controlling for baseline patient demographic and oncologic characteristics. Results Our cohort included 2,456 patients. Biopsies were positive in 1,257 (51.2%) patients, of whom 293 (23.3%) and 407 (32.4%) had high grade and volume disease, respectively. Median age of first shave was 17.0 years (interquartile range 16.0-19.0) and height was 177.7 cm (172.8-182.9). On multivariable analysis, later of age of first shave was significantly associated with increased odds of a positive prostate biopsy (odds ratio for >18 versus <16 years: 5.34, P=0.02) and taller patients had significantly increased odds of high grade cancer (odds ratio for 175-180 versus <175 cm: 7.46, P=0.037). Conclusions Amongst patients presenting for a prostate biopsy, those with a later age of first shave and taller height have an increased risk of a positive prostate biopsy and high grade prostate cancer, respectively.

Incidence and risk factors for mucormycosis in renal transplant patients.

Abstract: Background Renal transplant patients are at increased risk for mucormycosis. Diabetes, neutropenia, deferoxamine therapy, and immunosuppressive medications have been associated with increased risk of mucormycosis in studies of solid organ transplant recipients. To focus on renal transplant patients, the US Renal Data System (USRDS) was queried to determine the incidence and risk factors for mucormycosis. Methods All renal transplant patients in the USRDS from 1988 to 2015 were queried for a diagnosis of mucormycosis after the first transplant date using ICD-9 and ICD-10 codes. The International Classification of Diseases (ICD) codes, which currently exist in the ninth and tenth revisions, are a global system of classification used to code diagnoses, procedures, and symptoms. We defined proven mucormycosis by a histopathologic or fungal stain procedure code within 7 days of the diagnosis code. Logistic regression controlling for person-years at risk was used to examine demographic and clinical diagnosis risk factors for mucormycosis. Results Of the 306,482 renal transplant patients, 222 (0.07%) had codes consistent with proven mucormycosis. The incidence of mucormycosis increased from 1990 to 2000 (peak 17.6 per 100,000 person-years) and subsequently demonstrated more variability. Hispanic ethnicity (OR=1.45), age 65 years or greater (OR=1.64), other or black race compared with white race (OR=1.96 and 1.74), cadaver or other donor type (OR=2.41), and receiving tacrolimus (OR=2.09) were associated with increased risk. Comorbidities associated with decreased risk of mucormycosis included female sex (OR=0.68), iron overload (OR=0.56), and receiving mycophenolate mofetil (OR=0.67) or azathioprine (OR=0.53). Conclusions In renal transplant patients, age, deceased donor graft transplant, tacrolimus administration, race other than white, and Hispanic ethnicity were associated with increased risk of mucormycosis. Unexpectedly, iron overload was protective. Mucormycosis is a rare infection in renal transplant patients which should be considered in patients with the above risk factors after more common infections have been ruled out.