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https://www.readbyqxmd.com/read/28432788/structure-of-fam20a-reveals-a-pseudokinase-featuring-unique-disulfide-pattern-and-inverted-atp-binding
#1
Jixin Cui, Qinyu Zhu, Hui Zhang, Michael A Cianfrocco, Andres E Leschziner, Jack E Dixon, Junyu Xiao
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432751/acute-kidney-injury-plasma-lactate-concentrations-and-lactic-acidosis-in-metformin-users-a-godarts-study
#2
Paul J Connelly, Mike Lonergan, Enrique Soto-Pedre, Louise Donnelly, Kaixin Zhou, Ewan R Pearson
AIMS: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. METHODS: We undertook a population-based case-control study of lactic acidosis in 1,746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994-2014...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432745/safety-of-sitagliptin-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-outcomes-from-tecos
#3
Samuel S Engel, Shailaja Suryawanshi, Susanna R Stevens, Robert G Josse, Jan H Cornel, Neli Jakuboniene, Axel Riefflin, Tsvetalina Tankova, Julio Wainstein, Eric D Peterson, Rury R Holman
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR <60 mL/min per 1.73 m(2) ) versus those without CKD. Within the CKD cohort, the same analyses were performed comparing sitagliptin- and placebo-assigned participants...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432733/variability-in-hba1c-blood-pressure-lipid-parameters-and-serum-uric-acid-and-risk-of-development-of-chronic-kidney-disease-in-type-2-diabetes
#4
Antonio Ceriello, Salvatore De Cosmo, Maria Chiara Rossi, Giuseppe Lucisano, Stefano Genovese, Roberto Pontremoli, Paola Fioretto, Carlo Giorda, Antonio Pacilli, Francesca Viazzi, Giuseppina Russo, Antonio Nicolucci
AIMS: Variability in HbA1c and blood pressure (BP) is associated with the risk of diabetic kidney disease (DKD). No evidence exists on the role of variability in lipids or serum uric acid (UA), or the interplay between the variability of different parameters, on renal outcomes. MATERIALS AND METHODS: Within the AMD Annals database we identified patients with ≥5 measurements of HbA1c, SBP and DBP, total-, HDL- and LDL- cholesterol, triglycerides, and UA. Patients were followed-up for up to 5 years...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432726/combination-therapy-with-glp-1-receptor-agonist-and-sglt2-inhibitor
#5
REVIEW
Ralph A DeFronzo
The SGLT2 inhibitors (SGLTi) and glucagon-like-1 receptor agonists (GLP-1 RAs) effectively reduce HbA1c, but via very different mechanisms, making them an effective duet for combination therapy. Recently, drugs in both of these antidiabetic classes have been shown to reduce cardiovascular events, most likely by different mechanisms. SGLT2i appear to exert their CV protective actions by hemodynamic effects, while GLP-1 RAs work via anti-atherogenic/anti-inflammatory mechanisms, raising the possibility that combined therapy with these two classes may produce additive CV benefits...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432660/management-of-dyslipidemias-in-europe-and-the-usa-same-evidence-different-conclusions-can-we-find-common-ground
#6
REVIEW
Ian M Graham, Alberico L Catapano
PURPOSE OF REVIEW: An examination of the current ACC/AHA and ESC/EAS Guidelines on the management of dyslipidemias for common ground and differences. RECENT FINDINGS: There is much common ground. Both note that ASCVD is, in most people, the product of a number of risk factors, notably tobacco exposure, hyperlipidemia, hypertension, inactivity, overweight and diabetes. They stress that risk calculators can help in the assessment of risk in apparently healthy persons...
June 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28432469/renal-findings-in-patients-with-mulibrey-nanism
#7
Johanna Sivunen, Susann Karlberg, Jouko Lohi, Niklas Karlberg, Marita Lipsanen-Nyman, Hannu Jalanko
BACKGROUND: Mulibrey nanism (MUL) is a rare inherited disease caused by genetic defects affecting peroxisomal TRIM37 protein. MUL affects multiple organs, leading to growth retardation and early onset type 2 diabetes. We aimed to characterize the structure and function of kidneys and the urinary tract in a large cohort of Finnish MUL patients. METHODS: Ultrasound, magnetic resonance imaging (MRI), and autopsy findings of the kidneys and urinary tract from 101 MUL patients were retrospectively analyzed...
April 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28432319/diabetic-retinopathy-and-clinical-parameters-favoring-the-presence-of-diabetic-nephropathy-could-predict-renal-outcome-in-patients-with-diabetic-kidney-disease
#8
Chi-Chih Hung, Hugo You-Hsien Lin, Daw-Yang Hwang, I-Ching Kuo, Yi-Wen Chiu, Lee-Moay Lim, Shang-Jyh Hwang, Hung-Chun Chen
Diabetes duration, diabetic retinopathy (DR), and a diagnostic model have been proposed as clinical parameters favoring the presence of diabetic nephropathy (DN) in biopsied patients with diabetic kidney disease. DN, compared with non-diabetic renal disease, had poorer renal outcomes. We tested whether these clinical parameters favoring DN are associated with poorer renal outcomes in non-biopsied patients. In this study, 1330 patients with type 2 diabetes and chronic kidney disease stages 1-4 were included and divided according to diabetes mellitus (DM) duration >8 years, DR, or a diagnostic model for DN...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432167/a-tale-of-two-vasculitides-biopsy-proven-giant-cell-arteritis-followed-by-the-independent-development-of-renal-limited-microscopic-polyangiitis
#9
Roman Zuckerman, Mayur Patel, Deborah R Alpert
We describe an 80-year-old woman who presented with headaches, bilateral jaw claudication and visual symptoms. She was diagnosed with giant cell arteritis, which was confirmed by temporal artery biopsy. She was treated with high-dose prednisone followed by a slow taper, with complete resolution of symptoms. Approximately 4 years later, she developed progressively worsening renal function associated with haematuria. Serological workup revealed a high-titre perinuclear antinuclear cytoplasmic antibody and antibodies to myeloperoxidase...
April 21, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28432160/infective-endocarditis-in-octogenarians
#10
Léopold Oliver, Cécile Lavoute, Roch Giorgi, Erwan Salaun, Sandrine Hubert, Jean-Paul Casalta, Frédérique Gouriet, Sebastien Renard, Ludivine Saby, Jean-Francois Avierinos, Laurie-Anne Maysou, Alberto Riberi, Dominique Grisoli, Anne-Claire Casalta, Frédéric Collart, Didier Raoult, Gilbert Habib
OBJECTIVE: To describe the characteristics of infective endocarditis (IE) in octogenarians and assess their prognosis. METHODS: Patients with definite IE hospitalised at a referral centre between July 2008 and July 2013 were prospectively included. A total of 454 patients were divided into three groups: 230 patients under 65 years old, 173 patients between 65 and 80 years old, and 51 patients over 80 years old. The main end point was 1-year mortality. RESULTS: One-year mortality was higher in the ≥80 years old group (37...
April 21, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28431954/isolated-intracranial-fibromuscular-dysplasia-of-the-posterior-cerebral-artery
#11
Min-Ju Yeo, Ho-Yeong Jeon, Min-Ju Cha, Hye-Yeon Jang, Sang-Gil Lee, Ji Seon Kim, Sung-Hyun Lee, Sang-Soo Lee, Dong-Ick Shin
Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial disease that most commonly affects the renal and internal carotid arteries, but intracranial FMD is very rare. We report a patient with FMD involving the posterior cerebral arteries (PCAs). A 24year old female was presented with a 4day history of right homonymous hemianopsia with throbbing headache in the left temporo-occipital area. The brain magnetic resonance imaging (MRI) revealed an acute ischemic stroke in the left PCA territory, while the Time of Flight (TOF) magnetic resonance angiogram (MRA) showed segmental luminal irregularities in the left proximal PCA...
April 18, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28431934/etiological-analysis-and-epidemiological-comparison-among-adult-cap-and-nhcap-patients-in-okinawa-japan
#12
Gretchen Parrott, Daijiro Nebeya, Takeshi Kinjo, Kazuya Miyagi, Shusaku Haranaga, Futoshi Higa, Masao Tateyama, Jiro Fujita
BACKGROUND: Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues. METHODS: We retrospectively analyzed the etiology of 200 pneumonia patients at the University of the Ryukyus Hospital. Patients were categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese Respiratory Society guidelines. Diagnoses were made using clinical tests including, Gram stain, bacterial culture, serum and urinary tests...
April 18, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28431865/statin-use-and-other-factors-associated-with-mortality-after-major-lower-extremity-amputation
#13
Charles DeCarlo, Larry Scher, Saadat Shariff, John Phair, Evan Lipsitz, Karan Garg
OBJECTIVE: Above-knee amputations (AKAs) and below-knee amputations (BKAs) are associated with high postoperative mortality rates. In this study, we examined factors associated with 30-day, 90-day, and 1-year mortality in patients who underwent a major lower extremity amputation. METHODS: We queried a prospectively collected institutional database for all patients who underwent AKA or BKA with primary or secondary closure, during a 5-year period, between November 2009 and November 2014...
April 18, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28431773/atypical-moyamoya-syndrome-with-brain-calcification-and-stenosis-of-abdominal-aorta-and-renal-arteries
#14
Hideki Uchikawa, Katsunori Fujii, Mayuko Fujita, Tomoko Okunushi, Naoki Shimojo
Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen...
April 18, 2017: Brain & Development
https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#15
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28431597/cefepime-induced-encephalopathy-in-end-stage-renal-disease-patients
#16
Ryo Nakagawa, Kenichiro Sato, Yoshikazu Uesaka, Takashi Mitsuki, Kanya Kondo, Atsushi Wake, Yoshifumi Ubara, Mami Kanzaki
OBJECTIVES: Impaired renal function is a risk factor for cefepime (CFPM)-induced encephalopathy (CFPMIE) in patients treated with CFPM; dose-titration to renal function is recommended to prevent CFPMIE. However, available evidence on the incidence of CFPMIE or preventive efficacy of dose adjustment against CFPMIE in end-stage renal disease (ESRD) patients is limited. METHODS: Single-centre, retrospective observational study. We reviewed consecutive in-hospital adult patients treated with adjusted-dose of CFPM in the period between September 2012 and September 2016, and assessed the CFPMIE in ESRD patients treated with adjusted-dose of CFPM...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28431542/effects-of-periodontal-treatment-on-the-medical-status-of-patients-with-type-2-diabetes-mellitus-a-pilot-study
#17
Joichiro Hayashi, Akihiko Hasegawa, Kohei Hayashi, Takafumi Suzuki, Makiko Ishii, Hideharu Otsuka, Kazuhiro Yatabe, Seiichi Goto, Junichi Tatsumi, Kitetsu Shin
BACKGROUND: Studies have demonstrated that periodontal disease is associated with the development of systemic complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this pilot study was to investigate which markers among various systemic disease parameters are affected by periodontal treatment in patients with T2DM. METHODS: Twelve patients with T2DM were given oral hygiene instructions and subsequent subgingival scaling and root planing...
April 21, 2017: BMC Oral Health
https://www.readbyqxmd.com/read/28431476/a-consensus-statement-for-the-clinical-use-of-the-renal-sodium-glucose-co-transporter-2-inhibitor-dapagliflozin-in-patients-with-type-2-diabetes-mellitus
#18
A Avogaro, A Giaccari, P Fioretto, S Genovese, F Purrello, F Giorgino, S Del Prato
The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin ...
April 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28431381/zeaxanthin-ameliorates-high-glucose-induced-mesangial-cell-apoptosis-through-inhibiting-oxidative-stress-via-activating-akt-signalling-pathway
#19
Changjiang Ying, Lei Chen, Shanshan Wang, Yizhen Mao, Hongwei Ling, Wei Li, Xiaoyan Zhou
Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect...
April 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#20
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
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