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From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options.

Kidney Blood Press Res 2021 Jun 15:1-10. Epub 2021 Jun 15.

Department of Renal Medicine, St. George Hospital, Sydney, New South Wales, Australia.

Background: Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects. Read More

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Early detection of cognitive decline in mild cognitive impairment and Alzheimer's disease with a novel eye tracking test.

J Neurol Sci 2021 Jun 3;427:117529. Epub 2021 Jun 3.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address:

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0. Read More

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Three-dimensional mapping for His-bundle pacing in pediatric patients, a case series.

J Electrocardiol 2021 Jun 1;67:98-102. Epub 2021 Jun 1.

University of Minnesota/Masonic Children's Hospital, Minneapolis, USA; University of California at Davis, Sacramento, USA. Electronic address:

Introduction: Pediatric patients who receive pacemakers may have a lifetime of repeat exposure to fluoroscopy. His bundle pacing may provide better long-term pacing for these patients. To minimize fluoroscopy and for improved localization of the His bundle, we utilized three-dimensional mapping to guide His bundle pacing and we follow-up short-term results. Read More

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Trisomy 21 results in modest impacts on mitochondrial function and central carbon metabolism.

Free Radic Biol Med 2021 Jun 12. Epub 2021 Jun 12.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences; Linda Crnic Institute for Down Syndrome, School of Medicine, University of Colorado, Aurora, Colorado, USA. Electronic address:

Down syndrome (DS) is the most common genetic cause of intellectual disability. Mechanistically, oxidative stress and mitochondrial dysfunction are reported to be etiological factors for many of the DS-related comorbidities and have previously been reported in a number of in vitro and in vivo models of DS. The purpose of this study was to test for the presence of mitochondrial dysfunction in fibroblast cells obtained via skin biopsy from individuals with DS, and to assess the impact of trisomy 21 on central carbon metabolism. Read More

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In vivo bidirectional modulation of cannabinoid on the activity of globus pallidus in rats.

Neuroscience 2021 Jun 12. Epub 2021 Jun 12.

Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China. Electronic address:

Endocannabinoids are bioactive substances which participate in central motor control. The globus pallidus (GP) is a major nucleus in the basal ganglia circuit, which plays an important function in movement regulation. Both cannabinoid receptor type 1 (CBR) and cannabinoid receptor type 2 (CBR) are expressed in the GP suggesting GP as a main action area of endocannabinoids. Read More

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Preclinical evidence of synergism between atovaquone and chemotherapy by AMPK-dependent mitochondrial dysfunction.

Eur J Pharmacol 2021 Jun 12:174256. Epub 2021 Jun 12.

Department of Pulmonary and Critical Care Medicine, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China. Electronic address:

Chemoresistance has been associated with increased reliance on mitochondrial functions in many cancers, including lung cancer. Atovaquone is an anti-malaria drug and mitochondrial inhibitor. In this work, we attempted to explore whether atovaquone can be repurposed for lung cancer treatment to overcome chemoresistance. Read More

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PHF19 activates Hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma.

Exp Cell Res 2021 Jun 12:112690. Epub 2021 Jun 12.

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:

Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. Read More

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Evolution of an asymptomatic first stage of infection in a heterogeneous population.

J R Soc Interface 2021 Jun 16;18(179):20210175. Epub 2021 Jun 16.

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

Pathogens evolve different life-history strategies, which depend in part on differences in their host populations. A central feature of hosts is their population structure (e.g. Read More

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Event-related Beta EEG changes Induced by Various Neuromuscular Electrical Stimulation: A Pilot Study.

IEEE Trans Neural Syst Rehabil Eng 2021 Jun 15;PP. Epub 2021 Jun 15.

Previous results demonstrated that neuromuscular electrical stimulation (NMES) with various configurations could induce different activity at both the central and peripheral levels. Although NMES generating different peripheral movements have been studied, it is still unclear whether the difference in NMES-induced cortical activity is due to movement-or stimulation-related differences. Because NMES-induced cortical activity impacts motor function recovery, it is essential to know when NMES with various configurations evoke the same movement, whether the induced cortical activity is still different. Read More

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Cardiolipin Remodeling Defects Impair Mitochondrial Architecture and Function in a Murine Model of Barth Syndrome Cardiomyopathy.

Circ Heart Fail 2021 Jun 15;14(6):e008289. Epub 2021 Jun 15.

Department of Medicine (S.Z., Z.C., M.Z., S.S., C.T., Y.G., A.N., W.F., S.M.E., X.F.), University of California, San Diego, La Jolla.

Background: Cardiomyopathy is a major clinical feature in Barth syndrome (BTHS), an X-linked mitochondrial lipid disorder caused by mutations in (), encoding a mitochondrial acyltransferase required for cardiolipin remodeling. Despite recent description of a mouse model of BTHS cardiomyopathy, an in-depth analysis of specific lipid abnormalities and mitochondrial form and function in an in vivo BTHS cardiomyopathy model is lacking.

Methods: We performed in-depth assessment of cardiac function, cardiolipin species profiles, and mitochondrial structure and function in our newly generated cardiomyocyte-specific knockout mice and Cre-negative control mice (n≥3 per group). Read More

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Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.

Chem Rev 2021 Jun 15. Epub 2021 Jun 15.

Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Universidad Nacional de Rosario, Ocampo y Esmeralda S/N, 2000 Rosario, Argentina.

Antimicrobial resistance is one of the major problems in current practical medicine. The spread of genes coding for resistance determinants among bacteria challenges the use of approved antibiotics, narrowing the options for treatment. Resistance to carbapenems, last resort antibiotics, is a major concern. Read More

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Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress.

Mol Nutr Food Res 2021 Jun 15:e2100417. Epub 2021 Jun 15.

Y. Yuan, X. Chen, Y. Sun, Y. Fan, L. Zheng, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Scope: DNA methylation contributes to obesity, but the role of the DNA demethylase ten-eleven translocation protein 1 (Tet1) in obesity remains unclear. Vitamin C is a cofactor for the Tet family of proteins, but whether vitamin C can be used to treat obesity via Tet1 awaits clarification.

Methods And Results: Tet1 and Tet1 mice were fed a high fat diet (HFD). Read More

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Losartan Protects Podocytes against High Glucose-induced Injury by Inhibiting B7-1 Expression.

Curr Med Sci 2021 Jun 15. Epub 2021 Jun 15.

Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.

The role of B7-1 in podocyte injury has received increasing attention. The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease (DKD) by regulating B7-1 and the underlying mechanisms. Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks. Read More

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Bi-level Nasal Positive Airway Pressure (BiPAP) versus Nasal Continuous Positive Airway Pressure (CPAP) for Preterm Infants with Birth Weight Less Than 1500 g and Respiratory Distress Syndrome Following INSURE Treatment: A Two-center Randomized Controlled Trial.

Curr Med Sci 2021 Jun 15. Epub 2021 Jun 15.

Department of Neonatology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.

The present study aimed to examine the effectiveness of bi-level positive airway pressure (BiPAP) versus continuous positive airway pressure (CPAP) in preterm infants with birth weight less than 1500 g and respiratory distress syndrome (RDS) following intubation-surfactant-extubation (INSURE) treatment. A two-center randomized control trial was performed. The primary outcome was the reintubation rate of infants within 72 h of age after INSURE. Read More

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Chronic itch in African Americans: an unmet need.

Arch Dermatol Res 2021 Jun 15. Epub 2021 Jun 15.

Dr. Phillip Frost Department of Dermatology and Miami Itch Center, University of Miami, Miami, FL, USA.

Chronic pruritus carries a significant burden of disease and is associated with a negative impact on quality of life. African Americans are disproportionately burdened by chronic pruritic disorders, including but not limited to atopic dermatitis, prurigo nodularis, inflammatory scalp dermatoses, pathologic scarring, and HIV-related dermatoses. Racial differences in skin structure and function may contribute to the pathogenesis of itch in African Americans. Read More

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Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism.

Osteoporos Int 2021 Jun 15. Epub 2021 Jun 15.

Bone and Mineral Research Unit (ISPA) (REDinREN), Hospital Universitario Central Asturias, Oviedo University, Asturias, Spain.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m). The present article reports and summarizes the main recommendations included in this 2021 document. Read More

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Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake.

J Gen Physiol 2021 Aug 15;153(8). Epub 2021 Jun 15.

Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA.

Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The "glymphatic" mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. Read More

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Pythagorean Self-Awareness Intervention for Multiple Sclerosis Patients: A Quasi-Experimental Pragmatic Trial.

Arch Clin Neuropsychol 2021 Jun 15. Epub 2021 Jun 15.

1st Department of Neurology, Aeginition Hospital, Medical School, National Kapodistrian University of Athens, Athens, Greece.

Objective: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system affecting patients' well-being and quality of life. Pythagorean Self-Awareness Intervention (PSAI) is a novel non-pharmaceutical intervention with significant benefits both in MS and other chronic diseases. In this study, the longstanding effectiveness of PSAI was investigated. Read More

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High dimensional mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria.

JCI Insight 2021 Jun 15. Epub 2021 Jun 15.

Infectious Disease and Immune Defense, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

IFN-γ-driven responses to malaria have been shown to modulate the development and function of T follicular helper (TFH) cells and memory B cells (MBCs), with conflicting evidence in their involvement in the induction of antibody responses required to achieve clinical immunity and their association with disease outcomes. Using high-dimensional single cell mass cytometry, we identified distinct populations of TH1-polarized CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet, associated with either increased or reduced risk of Plasmodium vivax malaria, demonstrating that inflammatory responses to malaria are not universally detrimental for infection. Furthermore, we found that whereas class-switched but not IgM+ MBCs were associated with reduced risk of symptomatic malaria, populations of TH1 cells with a stem central memory phenotype, TH17 cells and T regulatory cells were associated with protection from asymptomatic infection, suggesting that activation of cell mediated immunity might be also required to control persistent P. Read More

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Upregulation of antigen presentation function and inflammation in chondrocytes by induction of proteoglycan aggrecan peptides (P16-31 and P263-280).

Clin Exp Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Immunology Division, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, and Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.

Objectives: A central hallmark of osteoarthritis (OA) is cartilage destruction. Chondrocytes not only control cartilage metabolism, but are capable of immunogenic responses. The role of chondrocytes in the pathogenesis of OA is still unclear. Read More

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Indoor simulation test research on cumulative longitudinal displacement of rail based on force and displacement sensors data collection.

Sci Prog 2021 Apr-Jun;104(2):368504211023287

School of Civil Engineering, Central South University, Changsha, Hunan, China.

The train sometimes needs to brake frequently on the turnout, although the braking force does not exceed the limit resistance of fastener, cumulative displacement of rail occurs because of the long-term effect of the train brakes, thus, the relationship between the cumulative displacement of rail and the number of train braking actions should be explored. Aiming at the spring bar type III fastener, a 1:1 physical indoor simulation test was carried out, and an electromagnetic relay device was used to simulate the train load, force, and displacement sensors for data collection. Then a single load no more than the maximum resistance of fastener was applied to the rail end to explore the relationship between the number of loads and the rail cumulative deformation. Read More

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Interleukin-25: New perspective and state-of-the-art in cancer prognosis and treatment approaches.

Cancer Med 2021 Jun 15. Epub 2021 Jun 15.

Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran.

Cancer is a leading cause of death which imposes a substantial financial burden. Among the several mechanisms involved in cancer progression, imbalance of immune cell-derived factors such as cytokines and chemokines plays a central role. IL-25, as a member of the IL-17 cytokine subfamily, exerts a paradoxical role in cancer, including tumor supportive and tumor suppressive. Read More

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The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

Eur Cell Mater 2021 Jun 15;41:707-738. Epub 2021 Jun 15.

Tissue Engineering for Orthopaedics and Mechanobiology (TOM), Department for BioMedical Research (DBMR) of the Faculty of Medicine of the University of Bern, University of Bern, Bern,

The intervertebral disc (IVD) is a complex tissue, and its degeneration remains a problem for patients, without significant improvement in treatment strategies. This mostly age-related disease predominantly affects the nucleus pulposus (NP), the central region of the IVD. The NP tissue, and especially its microenvironment, exhibit changes that may be involved at the outset or affect the progression of IVD pathology. Read More

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The effects of Ramadan intermittent fasting on sleep-wake behaviour and daytime sleepiness in team sport referees.

J Sports Sci 2021 Jun 15:1-7. Epub 2021 Jun 15.

Institut Supérieur Du Sport Et De L'éducation Physique De Sfax, Université De Sfax, Sfax, Tunisie.

The aim of the present study was to evaluate the impact of Ramadan fasting on sleep quality and daytime sleepiness in team sport referees. Seventy-eight male amateur team sport referees (age: 31.1 ± 10. Read More

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Cyclic nucleotide-dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull-push sensitivity modulation.

Eur J Neurosci 2021 Jun 14. Epub 2021 Jun 14.

Biologie, Tierphysiologie, Philipps-Universität Marburg, Marburg, Germany.

Olfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP- and adapt via cGMP-dependent mechanisms. Perforated patch clamp recordings distinguished eleven currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K currents and two non-specific cation currents. Read More

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Stock structure analysis of the endemic fish, Barbodes carnaticus (Jerdon 1849), for conservation in a biodiversity hotspot.

Environ Sci Pollut Res Int 2021 Jun 15. Epub 2021 Jun 15.

ICAR-Central Institute of Fisheries Education, Mumbai, India.

The population structure of Barbodes carnaticus species was studied using conventional (based on body morphometrics and meristic) and image-based analysis (truss network system) methods. The study was carried out with four stocks, namely Karnataka (KA) and Tamil Nadu (TN) stocks from the River Cauvery, Kerala (KE) stock from the River Chalakudy and farm-reared stock (CI) from Central Institute of Freshwater Aquaculture, Bangalore. A total of 27 morphometric, 9 meristic and 30 truss measurements were used in the study for the stock structure. Read More

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Therapeutic potential of ginsenoside Rg3 and Rf for Huntington's disease.

In Vitro Cell Dev Biol Anim 2021 Jun 14. Epub 2021 Jun 14.

Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.

Ginseng is a popular herbal medicine and known to have protective and therapeutic effects in various diseases. Ginsenosides are active gradients representing the diverse pharmacological efficacy of ginseng. Huntington's disease (HD) is incurable genetic disorder associated with mutant huntingtin (mHtt) aggregation in the central nervous system. Read More

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Modeling the risk of radiation pneumonitis in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

Esophagus 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China.

Background: To develop and validate a nomogram for the prediction of symptomatic radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received definitive concurrent chemoradiotherapy.

Methods: Clinical factors, dose-volume histogram parameters, and pulmonary function parameters were collected from 402 ESCC patients between 2010 and 2017, including 321 patients in the primary cohort and 81 in the validation cohort. The end-point was the occurrence of symptomatic RP (grade ≥ 2) within the first 12 months after radiotherapy. Read More

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Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index.

Sci Rep 2021 Jun 14;11(1):12469. Epub 2021 Jun 14.

Neurorehabilitation Research Institute, Morinomiya Hospital, Osaka, 536-0025, Japan.

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. Read More

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Pseudogene ACTBP2 increases blood-brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ microenvironment.

Cell Death Discov 2021 Jun 14;7(1):142. Epub 2021 Jun 14.

Department of Neurobiology, School of life Sciences, China Medical University, Shenyang, China.

The blood-brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer's disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. Read More

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