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https://www.readbyqxmd.com/read/28427321/in-silico-assessment-of-biomedical-products-the-conundrum-of-rare-but-not-so-rare-events-in-two-case-studies
#1
Marco Viceconti, Claudio Cobelli, Tarek Haddad, Adam Himes, Boris Kovatchev, Mark Palmer
In silico clinical trials, defined as "The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention," have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern...
May 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28426193/the-glutathione-conundrum-stoichiometric-disconnect-between-its-formation-and-oxidative-stress
#2
Gunnar Boysen
Glutathione (GSH) is the most abundant antioxidant and is believed to maintain redox potential in tissues, cells, and individual compartments. However, GSH concentrations in some tumor cells and tissues have been reported to be as high as 1-10 mM, a concentration that is up to 10,000-fold higher than that of reactive oxygen species. Critical quantitative evaluation of glutathione's proposed functions suggests that glutathione is an amino acid checkpoint. In this role, glutathione contributes to regulating cell proliferation and apoptosis, pending amino acid availability...
April 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28424763/airway-problems-in-neonates-a-review-of-the-current-investigation-and-management-strategies
#3
REVIEW
Quen Mok
Airway problems in the neonatal population are often life threatening and raise challenging issues in diagnosis and management. The airway problems can result from congenital or acquired lesions and can be broadly classified into those causing obstruction or those due to an abnormal "communication" in the airway. Many different investigations are now available to identify the diagnosis and quantify the severity of the problem, and these tests can be simple or invasive. Bronchography and bronchoscopy are essential to determine the extent and severity of the airway problem and to plan treatment strategy...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28422932/clarifying-the-conundrum-evidence-based-practice-quality-improvement-or-research-the-clinical-scholarship-continuum
#4
Eileen J Carter, Kari Mastro, Courtney Vose, Reynaldo Rivera, Elaine L Larson
Nurses' active involvement in clinical scholarship is necessary to advance the nursing profession and improve patient outcomes. Yet, definitional confusion and numerous barriers exist to clinical scholarship in and across academic and patient care settings. We discuss factors that pose barriers to the continuum of clinical scholarship and suggest opportunities for clinician-researcher collaborations that promote nurses' engagement in evidence-based practice, quality improvement, and research.
May 2017: Journal of Nursing Administration
https://www.readbyqxmd.com/read/28421268/using-a-population-model-to-inform-the-management-of-river-flows-and-invasive-carp-cyprinus-carpio
#5
John D Koehn, Charles R Todd, Brenton P Zampatti, Ivor G Stuart, Anthony Conallin, Leigh Thwaites, Qifeng Ye
Carp are a highly successful invasive fish species, now widespread, abundant and considered a pest in south-eastern Australia. To date, most management effort has been directed at reducing abundances of adult fish, with little consideration of population growth through reproduction. Environmental water allocations are now an important option for the rehabilitation of aquatic ecosystems, particularly in the Murray-Darling Basin. As carp respond to flows, there is concern that environmental watering may cause floodplain inundation and provide access to spawning habitats subsequently causing unwanted population increase...
April 18, 2017: Environmental Management
https://www.readbyqxmd.com/read/28418116/-what-is-the-point-of-life-an-interpretative-phenomenological-analysis-of-suicide-in-young-menwith-first-episode-psychosis
#6
Ruchika Gajwani, Michael Larkin, Chris Jackson
BACKGROUND: Lifetime risk of suicide in first-episode psychosis far exceeds the general population, with the risk of suicide persisting long after first presentation. There is strong evidence to suggest that women more frequently attempt suicide, while men are at a greater risk of completing suicide. First-hand experiential evidence is needed in order to better understand men's motives for, and struggles with, suicidality in early psychosis. METHODS: Semi-structured interviews were conducted with 7 participants...
April 18, 2017: Early Intervention in Psychiatry
https://www.readbyqxmd.com/read/28414101/autophagy-in-hemorrhagic-stroke-mechanisms-and-clinical-implications
#7
REVIEW
Haiying Li, Jiang Wu, Haitao Shen, Xiyang Yao, Chenglin Liu, S Pianta, J Han, C V Borlongan, Gang Chen
Accumulating evidence advances the critical role of autophagy in brain pathology after stroke. Investigations employing autophagy induction or inhibition using pharmacological tools or autophagy-related gene knockout mice have recently revealed the biological significance of intact and functional autophagy in stroke. Most of the reported cases attest to a pro-survival role for autophagy in stroke, by facilitating removal of damaged proteins and organelles, which can be recycled for energy generation and cellular defenses...
April 13, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28406147/transcriptome-analyses-of-differential-gene-expression-in-the-bursa-of-fabricius-between-silky-fowl-and-white-leghorn
#8
Deping Han, Yuanyuan Zhang, Jianfei Chen, Guoying Hua, Junying Li, Xuegong Deng, Xuemei Deng
Hyperpigmentation in Silky Fowl (SF) results in aberrant immune cell development. However, how melanocytes regulate B-cell proliferation in the bursa of Fabricius (BF) is unclear. To resolve this conundrum, we collected BFs from three-week-old SF and White Leghorn (WL) female chickens for RNA sequencing. The BF development was relatively weaker in SF than in WL. The transcriptome analyses identified 4848 differentially expressed genes, 326 long noncoding RNAs (lncRNAs), and 67 microRNAs in the BF of SF. The genes associated with melanogenesis was significantly higher, but that of the genes associated with the cytokine-cytokine receptor interactions and JAK-STAT signalling pathway was significantly lower in SF than in WL...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404606/local-translation-in-neuronal-compartments-how-local-is-local
#9
REVIEW
Vidhya Rangaraju, Susanne Tom Dieck, Erin M Schuman
Efficient neuronal function depends on the continued modulation of the local neuronal proteome. Local protein synthesis plays a central role in tuning the neuronal proteome at specific neuronal regions. Various aspects of translation such as the localization of translational machinery, spatial spread of the newly translated proteins, and their site of action are carried out in specialized neuronal subcompartments to result in a localized functional outcome. In this review, we focus on the various aspects of these local translation compartments such as size, biochemical and organelle composition, structural boundaries, and temporal dynamics...
April 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28401387/quantifying-microplastic-pollution-on-sandy-beaches-the-conundrum-of-large-sample-variability-and-spatial-heterogeneity
#10
Mara Fisner, Alessandra P Majer, Danilo Balthazar-Silva, Daniel Gorman, Alexander Turra
Despite the environmental risks posed by microplastic pollution, there are presently few standardized protocols for monitoring these materials within marine and coastal habitats. We provide a robust comparison of methods for sampling microplastics on sandy beaches using pellets as a model and attempt to define a framework for reliable standing stock estimation. We performed multiple comparisons to determine: (1) the optimal size of sampling equipment, (2) the depth to which samples should be obtained, (3) the optimal sample resolution for cross-shore transects, and (4) the number of transects required to yield reproducible along-shore estimates across the entire sections of a beach...
April 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28400119/bile-acids-and-colon-cancer-is-fxr-the-solution-of-the-conundrum
#11
REVIEW
Raffaella Maria Gadaleta, Oihane Garcia-Irigoyen, Antonio Moschetta
Diet and lifestyle habits have a profound impact on the pathophysiology of many diseases. Colorectal cancer (CRC) is the third most common cancer worldwide and its etiology is strongly influenced by nutrition and high fat/high carbohydrate Western-style diet. Human epidemiological and animal studies have shown that colonic cancer risk is also related to faecal bile acid concentration. Abnormally high levels of bile acids (BA) trigger the colonic mucosa with a plethora of detrimental effects such as DNA oxidative damage, inflammation and hyperproliferation that highly promote CRC progression in post-initiation phase...
April 8, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28397768/lysozyme-associated-liposomal-gentamicin-inhibits-bacterial-biofilm
#12
Yilin Hou, Zhaojie Wang, Peng Zhang, Hu Bai, Yuelin Sun, Jinyou Duan, Haibo Mu
Bacteria on living or inert surfaces usually form biofilms which make them highly resistant to antibiotics and immune clearance. Herein, we develop a simple approach to overcome the above conundrum through lysozyme-associated liposomal gentamicin (LLG). The association of lysozyme to the surface of liposomes can effectively reduce the fusion of liposomes and undesirable payload release in regular storage or physiological environments. The LLG was more effective at damaging established biofilms and inhibiting biofilm formation of pathogens including Gram-positive and Gram-negative bacteria than gentamicin alone...
April 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396716/tumor-reactive-stroma-in-cholangiocarcinoma-the-fuel-behind-cancer-aggressiveness
#13
EDITORIAL
Simone Brivio, Massimiliano Cadamuro, Mario Strazzabosco, Luca Fabris
Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases)...
March 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28391756/problems-in-mitochondrial-dna-forensics-while-interpreting-length-heteroplasmy-conundrum-of-various-sindhi-and-baluchi-ethnic-groups-of-pakistan
#14
Shahzad Bhatti, Muhammad Aslam Khan, Sana Abbas, Marcella Attimonelli, Gerardo Rodriguez Gonzalez, Hikmet Hakan Aydin, Erica Martinha Silva de Souza
The insight heterodox genetics of mtDNA infer new perspectives at the level of human mitochondrial control region heteroplasmy, which is substantial in evolutionary as well as forensic interpretation. The main goal of this study is to interrogate the recurrence and resolve the ambiguity of blurry spectrum of heteroplasmy in the human mtDNA control region of 50 Baluchi and 116 Sindhi unrelated individuals. Sanger sequencing was employed classically, that was further investigated by minisequencing. Only 20% Baluchi and 25...
April 9, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28391338/what-are-we-missing-in-the-clinical-trials-of-focal-segmental-glomerulosclerosis
#15
Ladan Zand, Richard J Glassock, An S De Vriese, Sanjeev Sethi, Fernando C Fervenza
Focal segmental glomerulosclerosis (FSGS) is a lesion and not a disease. This conundrum is the crux of controversies regarding interventions to alter its natural history. In the broadest sense, the lesion can be primary (idiopathic), or secondary to a process originating outside the kidneys or to a genetic mutation. The organ-based target is the podocyte, and the mechanisms responsible for the podocytopathy are numerous and diverse. Recurrence of primary FSGS in renal allografts provides the best evidence for the existence of a circulating factor or factors, the nature of which remains uncertain...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28386492/a-case-of-recurrent-skin-abscesses-a-conundrum-solved-after-obtaining-a-thorough-sexual-history
#16
Diego P Peralta, Aymara Y Chang, Enrique Soto-Ruiz
Background. Despite the improvement in patient-physician communication techniques, sexuality and sexual health continue to be challenging areas for discussion during a clinical encounter. Most people are not prepared to discuss sexual matters openly as it can be perceived as negative or inappropriate. Consequently, an incomplete health assessment can result in delayed diagnosis or misdiagnosis. Case Report. We present a 33-year-old woman who developed recurrent left breast abscesses. She required multiple incision and drainage procedures in the operating room followed by antimicrobial therapy...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28376097/geospatial-characteristics-of-measles-transmission-in-china-during-2005-2014
#17
Wan Yang, Liang Wen, Shen-Long Li, Kai Chen, Wen-Yi Zhang, Jeffrey Shaman
Measles is a highly contagious and severe disease. Despite mass vaccination, it remains a leading cause of death in children in developing regions, killing 114,900 globally in 2014. In 2006, China committed to eliminating measles by 2012; to this end, the country enhanced its mandatory vaccination programs and achieved vaccination rates reported above 95% by 2008. However, in spite of these efforts, during the last 3 years (2013-2015) China documented 27,695, 52,656, and 42,874 confirmed measles cases. How measles manages to spread in China-the world's largest population-in the mass vaccination era remains poorly understood...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28370500/editorial-the-conundrum-of-calcified-coronaries
#18
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/28370280/the-diversity-segregation-conundrum
#19
Richard Florida
There is a long literature extolling the virtues of diversity for both the civility and economic performance of nations and cities. On the most basic level, diversity helps nations and cities attract the wide range of creative talent that drives innovation and economic growth. Yet similarly, there is a large amount of literature on the sorting and segregation of different types of people into distinct communities. This in turn undermines the very mixing of people and groups required for economic prosperity to flourish...
April 3, 2017: American Journal of Community Psychology
https://www.readbyqxmd.com/read/28366222/infections-of-the-spine
#20
REVIEW
Maja Babic, Claus S Simpfendorfer
Pyogenic infections of the bony spinal column and the intervertebral discs are on a steady rise in an aging western population. Despite advanced medical imaging, this clinical entity of devastating consequences if missed, still presents a diagnostic conundrum and is plagued by an unacceptably long diagnostic delay. The aim of this article is to raise awareness of the heterogeneity of spinal infections paralleling the complex structure of the spinal column and neighboring soft tissues. Emphasis is placed on the clinical presentation and management of septic facet joints and psoas muscle abscesses associated with lumbar spondylodiscitis...
March 30, 2017: Infectious Disease Clinics of North America
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