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https://www.readbyqxmd.com/read/28727823/structural-instability-of-large-scale-functional-networks
#1
Shogo Mizutaka, Kousuke Yakubo
We study how large functional networks can grow stably under possible cascading overload failures and evaluated the maximum stable network size above which even a small-scale failure would cause a fatal breakdown of the network. Employing a model of cascading failures induced by temporally fluctuating loads, the maximum stable size nmax has been calculated as a function of the load reduction parameter r that characterizes how quickly the total load is reduced during the cascade. If we reduce the total load sufficiently fast (r ≥ rc), the network can grow infinitely...
2017: PloS One
https://www.readbyqxmd.com/read/28722141/failure-to-rescue-as-a-nurse-sensitive-indicator
#2
Jane Mushta, Kathy L Rush, Elizabeth Andersen
PROBLEM: The aim of this concept analysis was to clarify failure to rescure as a nurse-sensitive indicator. Although the concept of failure to rescue as a nurse-sensitive outcome has appeared in the nursing literature for over a decade, conceptual clarity is needed to address its variable and ambiguous use in health care. METHODS: Walker and Avant's eight-stage method of concept analysis was used to explore the concept of failure to rescue in nursing practice. Twenty-one papers were retrieved from Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE databases and selected for review and synthesis...
July 19, 2017: Nursing Forum
https://www.readbyqxmd.com/read/28711594/hepatic-mitochondrial-bioenergetics-in-aged-c57bl-6-mice-exhibit-delayed-recovery-from-severe-burn-injury
#3
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Marc G Jeschke
Severe burn injuries initiate a cascade of downstream events, culminating in multiple organ dysfunction, sepsis, and even death. The elderly are in particular vulnerable to such outcomes, due primarily to a scarcity of knowledge on trauma progression at the biomolecular level in this population. Mitochondria, the cellular powerhouses, have been increasingly scrutinized recently for their contribution to trauma outcomes. We hypothesized that elderly have a worse outcome compared to adult patients due to failed recovery of hepatic mitochondria...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28698549/a-tissue-engineered-model-of-aging-interdependence-and-cooperative-effects-in-failing-tissues
#4
A Acun, D C Vural, P Zorlutuna
Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684793/differentiating-staphylococcus-aureus-from-escherichia-coli-mastitis-s-aureus-triggers-unbalanced-immune-dampening-and-host-cell-invasion-immediately-after-udder-infection
#5
Juliane Günther, Wolfram Petzl, Isabel Bauer, Siriluck Ponsuksili, Holm Zerbe, Hans-Joachim Schuberth, Ronald M Brunner, Hans-Martin Seyfert
The etiology determines quality and extent of the immune response after udder infection (mastitis). Infections with Gram negative bacteria (e.g. Escherichia coli) will quickly elicit strong inflammation of the udder, fully activate its immune defence via pathogen receptor driven activation of IκB/NF-κB signaling. This often eradicates the pathogen. In contrast, Gram-positive bacteria (e.g. Staphylococcus aureus) will slowly elicit a much weaker inflammation and immune response, frequently resulting in chronic infections...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678521/restoration-of-megalin-mediated-clearance-of-alveolar-protein-as-a-novel-therapeutic-approach-for-acute-lung-injury
#6
Christine U Vohwinkel, Yasmin Buchäckert, Hamza M Al-Tamari, Luciana C Mazzocchi, Holger K Eltzschig, Konstantin Mayer, Rory E Morty, Susanne Herold, Werner Seeger, Soni S Pullamsetti, István Vadász
Acute respiratory distress syndrome (ARDS) constitutes a significant disease burden with regard to both morbidity and mortality. Current therapies are mostly supportive and do not address the underlying pathophysiologic mechanisms. Removal of protein-rich alveolar edema - a clinical hallmark of ARDS - is critical for survival. Here, we describe a TGFβ-triggered mechanism, in which megalin, the primary mediator of alveolar protein transport, is negatively regulated by GSK3β, with protein phosphatase 1 (PP1) and nuclear inhibitor of PP1 being involved in the signaling cascade...
July 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28675640/characterization-of-serum-proteins-attached-to-distinct-sol-gel-hybrid-surfaces
#7
Nuno Araújo-Gomes, Francisco Romero-Gavilán, Ana M Sánchez-Pérez, Marilo Gurruchaga, Mikel Azkargorta, Felix Elortza, María Martinez-Ibañez, Ibon Iloro, Julio Suay, Isabel Goñi
The success of a dental implant depends on its osseointegration, an important feature of the implant biocompatibility. In this study, two distinct sol-gel hybrid coating formulations [50% methyltrimethoxysilane: 50% 3-glycidoxypropyl-trimethoxysilane (50M50G) and 70% methyltrimethoxysilane with 30% tetraethyl orthosilicate (70M30T)] were applied onto titanium implants. To evaluate their osseointegration, in vitro and in vivo assays were performed. Cell proliferation and differentiation in vitro did not show any differences between the coatings...
July 4, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28673566/cancer-is-an-adaptation-that-selects-in-animals-against-energy-dissipation
#8
Anthonie W J Muller
As cancer usually follows reproduction, it is generally assumed that cancer does not select. Graham has however argued that juvenile cancer, which precedes reproduction, could during evolution have implemented a "cancer selection" that resulted in novel traits that suppress this juvenile cancer; an example is protection against UV sunlight-induced cancer, required for the emergence of terrestrial animals from the sea. We modify the cancer selection mechanism to the posited "cancer adaptation" mechanism, in which juvenile mortality is enhanced through the diminished care received by juveniles from their (grand) parents when these suffer from cancer in old age...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28670735/six3-deletions-and-incomplete-penetrance-in-families-affected-by-holoprosencephaly
#9
Bethany Stokes, Seth I Berger, Beth A Hall, Karin Weiss, Donald W Hadley, David R Murdock, Subhadra Ramanathan, Robin D Clark, Erich Roessler, Paul Kruszka, Maximilian Muenke
Holoprosencephaly (HPE) is failure of the forebrain to divide completely during embryogenesis. Incomplete penetrance has not been reported previously in SIX3 whole gene deletions which are known to cause HPE. Both chromosomal microarray and whole exome sequencing (WES) were used to evaluated families with inherited HPE. Two families showed inherited deletions that contain SIX3 and were incompletely penetrant for HPE. Using WES, we ruled out parental mosaicism, a SIX3 hypomorph, and clinically significant variants in genes that are known to interact with SIX3 as causes of incomplete penetrance...
July 2, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28670625/mechanisms-of-acetaminophen-hepatotoxicity-and-their-translation-to-the-human-pathophysiology
#10
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and mechanisms of liver injury induced by APAP overdose have been the focus of extensive investigation. Studies in the mouse model, which closely reproduces the human condition, have shown that hepatotoxicity is initiated by formation of a reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which depletes cellular glutathione and forms protein adducts on mitochondrial proteins. This leads to mitochondrial oxidative and nitrosative stress, accompanied by activation of c-jun N-terminal kinase (JNK) and its translocation to the mitochondria...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28669108/novel-genetic-variants-in-bag3-and-tnnt2-in-a-swedish-family-with-a-history-of-dilated-cardiomyopathy-and-sudden-cardiac-death
#11
Eva Fernlund, A Wålinder Österberg, E Kuchinskaya, M Gustafsson, K Jansson, C Gunnarsson
Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy...
July 1, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28648366/-oxidative-stress-in-perinatal-asphyxia-and-hypoxic-ischaemic-encephalopathy
#12
Antonio Nuñez, Isabel Benavente, Dorotea Blanco, Héctor Boix, Fernando Cabañas, Mercedes Chaffanel, Belén Fernández-Colomer, José Ramón Fernández-Lorenzo, Begoña Loureiro, María Teresa Moral, Antonio Pavón, Inés Tofé, Eva Valverde, Máximo Vento
Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways...
June 22, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28628948/platelet-hyperaggregability-is-associated-with-decreased-adamts13-activity-and-enhanced-endotoxemia-in-patients-with-acute-cholangitis
#13
Hiroaki Takaya, Hideto Kawaratani, Takuya Kubo, Kenichiro Seki, Yasuhiko Sawada, Kosuke Kaji, Yasushi Okura, Kosuke Takeda, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Akira Mitoro, Masanori Matsumoto, Hiroshi Fukui, Hitoshi Yoshiji
AIM: Insufficient ADAMTS13 activity (ADAMTS13:AC) leads to increased levels of unusually large von Willebrand factor (VWF) multimers and causes microcirculatory disturbance and multiple organ failure (MOF). Endotoxin (Et) triggers the activation of coagulation and cytokine cascades, leading to MOF in severe inflammatory response syndrome (SIRS). Here, we investigated the potential role of endotoxemia-related ADAMTS13 in acute cholangitis. METHODS: Twenty-four patients with acute cholangitis, including 7 with severe acute cholangitis, were recruited in this study...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28626800/dna-damage-induced-nuclear-factor-kappa-b-activation-and-its-roles-in-cancer-progression
#14
Wei Wang, Arul M Mani, Zhao-Hui Wu
DNA damage is a vital challenge to cell homeostasis. Cellular responses to DNA damage (DDR) play essential roles in maintaining genomic stability and survival, whose failure could lead to detrimental consequences such as cancer development and aging. Nuclear factor-kappa B (NF-κB) is a family of transcription factors that plays critical roles in cellular stress response. Along with p53, NF-κB modulates transactivation of a large number of genes which participate in various cellular processes involved in DDR...
2017: Journal of Cancer Metastasis and Treatment
https://www.readbyqxmd.com/read/28612487/anagen-effluvium-in-association-with-extracorporeal-membrane-oxygenation
#15
Lisa Cotter, Kyle Cheng, Anna Yasmine Kirkorian
Anagen effluvium (AE) is a type of alopecia with hair loss during the growth phase of a hair follicle and is most often associated with cytotoxic chemotherapy. This report describes a case of AE in a critically ill 2-year-old boy who developed cardiorespiratory failure requiring extracorporeal membranous oxygenation. We postulate that the combination of hypotension and hypoxia with subsequent reperfusion triggered an apoptotic cascade in the hair matrix, resulting in AE.
June 13, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28604492/a-microstructural-investigation-of-disc-disruption-induced-by-low-frequency-cyclic-loading
#16
Meredith L Schollum, Kelly R Wade, Peter A Robertson, Ashvin Thambyah, Neil D Broom
STUDY DESIGN: Microstructural investigation of low frequency cyclic loading and flexing of the lumbar disc. OBJECTIVE: To explore micro-level structural damage in motion segments subjected to low frequency repetitive loading and flexing at sub-acute loads. SUMMARY OF BACKGROUND DATA: Cumulative exposure to mechanical load has been implicated in low back pain and injury. The mechanical pathways by which cyclic loading physically affects spine tissues remain unclear, in part due to the absence of high quality microstructural evidence...
June 9, 2017: Spine
https://www.readbyqxmd.com/read/28603208/ultra-early-phase-pathologies-of-alzheimer-s-disease-and-other-neurodegenerative-diseases
#17
REVIEW
Hitoshi Okazawa
The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28602971/new-developments-in-hepatorenal-syndrome
#18
Ayse L Mindikoglu, Stephen C Pappas
Hepatorenal Syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain due to the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal function. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to more accurately estimate true GFR...
June 7, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28598381/renin-inhibition-with-aliskiren-a-decade-of-clinical-experience
#19
REVIEW
Nikolaos-Dimitrios Pantzaris, Evangelos Karanikolas, Konstantinos Tsiotsios, Dimitrios Velissaris
The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of arterial hypertension as well as in more complex mechanisms of cardiovascular and renal diseases. RAAS-blocking agents like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, have long been key components in the treatment of essential hypertension, heart failure, diabetic nephropathy, and chronic kidney disease, showing benefits well beyond blood pressure reduction. Renin blockade as the first step of the RAAS cascade finally became possible in 2007 with the approval of aliskiren, the first orally active direct renin inhibitor available for clinical use and the newest antihypertensive agent on the market...
June 9, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28586203/why-is-research-on-amyloid-%C3%AE-failing-to-give-new-drugs-for-alzheimer-s-disease
#20
Andrew J Doig, Maria P Del Castillo-Frias, Olivia Berthoumieu, Bogdan Tarus, Jessica Nasica-Labouze, Fabio Sterpone, Phuong H Nguyen, Nigel M Hooper, Peter Faller, Philippe Derreumaux
The two hallmarks of Alzheimer's disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure...
June 6, 2017: ACS Chemical Neuroscience
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