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https://www.readbyqxmd.com/read/28202028/management-of-everolimus-associated-adverse-events-in-patients-with-tuberous-sclerosis-complex-a-practical-guide
#1
REVIEW
Mark Davies, Anurag Saxena, John C Kingswood
Tuberous sclerosis complex (TSC) is a genetic disorder characterised by highly variable comorbid dysfunction and subsequent morbidity. The mTOR inhibitor everolimus is indicated for the treatment of adult TSC patients with renal angiomyolipomas (AMLs) and for subependymal giant astrocytoma (SEGA) in both adults and children, based on data from the EXIST-1 and EXIST-2 trials. However, due to the historical predominance of everolimus in the oncology setting, some physicians who treat TSC patients may be unfamiliar with everolimus-associated adverse events (AEs) and appropriate management strategies...
February 15, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28195652/identification-of-the-anti-mycobacterial-functional-properties-of-piperidinol-derivatives
#2
Collette S Guy, Esther Tichauer, Gemma L Kay, Daniel J Phillips, Trisha L Bailey, James Harrison, Christopher M Furze, Andrew D Millard, Matthew I Gibson, Mark J Pallen, Elizabeth Fullam
BACKGROUND AND PURPOSE: Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate and new anti-tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug-resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. EXPERIMENTAL APPROACH: The antibacterial properties of the piperidinol compound and its corresponding bis-Mannich base analogue were evaluated against Mycobacterium smegmatis and Gram-negative organisms...
February 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28179408/time-resolved-global-and-chromatin-proteomics-during-herpes-simplex-virus-hsv-1-infection
#3
Katarzyna Kulej, Daphne C Avgousti, Simone Sidoli, Christin Herrmann, Ashley N Della Fera, Eui Tae Kim, Benjamin A Garcia, Matthew D Weitzman
Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection...
February 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28144662/potato-virus-x-a-filamentous-plant-viral-nanoparticle-for-doxorubicin-delivery-in-cancer-therapy
#4
Duc H T Le, Karin L Lee, Sourabh Shukla, Ulrich Commandeur, Nicole F Steinmetz
Plant viral nanoparticles (VNPs) are a novel class of nanocarriers with implications for drug delivery in cancer therapy. VNPs are characterized by their highly symmetrical nanoscale structures. Furthermore, plant VNPs are biocompatible, biodegradable, and non-infectious in mammals. VNPs provide a proteinaceous platform technology that can be readily engineered to carry contrast agents and therapies using chemical and genetic modifications. Of particular interest are high aspect ratio, elongated filaments such as the ones formed by potato virus X (PVX, measuring 515 × 13 nm)...
February 9, 2017: Nanoscale
https://www.readbyqxmd.com/read/28131867/a-rapid-orthopoxvirus-purification-protocol-suitable-for-high-containment-laboratories
#5
Laura Hughes, Kimberly Wilkins, Cynthia S Goldsmith, Scott Smith, Paul Hudson, Nishi Patel, Kevin Karem, Inger Damon, Yu Li, Victoria A Olson, P S Satheshkumar
Virus purification in a high-containment setting provides unique challenges due to barrier precautions and operational safety approaches that are not necessary in lower biosafety level (BSL) 2 environments. The need for high risk group pathogen diagnostic assay development, anti-viral research, pathogenesis and vaccine efficacy research necessitates work in BSL-3 and BSL-4 labs with infectious agents. When this work is performed in accordance with BSL-4 practices, modifications are often required in standard protocols...
January 26, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28123631/non-invasive-administration-of-biodegradable-nano-carrier-vaccines
#6
REVIEW
Mohd Abul Kalam, Abdul Arif Khan, Aws Alshamsan
Polymeric nanoparticulate carriers play an important role and holding a significant potential for the development of novel immunomodulatory agents as easily they are taken up by antigen presenting cells. They allow an enhanced antigen stability, better immunogenicity and immunostimulatory effect with sustained and controlled release of the antigen to the target sites. Better information and vital understanding of mechanism of action, interaction of such vectors with the APCs and dendritic cells and antigen release kinetics in immunomodulatory effects, and improved knowledge of their in vivo fate and distribution are now needed, those collectively would speed up the rational strategies of nanoparticles as carriers for vaccines and other protein antigens...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28123094/species-decline-under-nitrogen-fertilization-increases-community-level-competence-of-fungal-diseases
#7
Xiang Liu, Shengman Lyu, Dexin Sun, Corey J A Bradshaw, Shurong Zhou
The artificial fertilization of soils can alter the structure of natural plant communities and exacerbate pathogen emergence and transmission. Although the direct effects of fertilization on disease resistance in plants have received some research attention, its indirect effects of altered community structure on the severity of fungal disease infection remain largely uninvestigated. We designed manipulation experiments in natural assemblages of Tibetan alpine meadow vegetation along a nitrogen-fertilization gradient over 5 years to compare the relative importance of direct and indirect effects of fertilization on foliar fungal infections at the community level...
January 25, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28115686/gender-based-differences-in-water-sanitation-and-hygiene-related-diarrheal-disease-and-helminthic-infections-a-systematic-review-and-meta-analysis
#8
REVIEW
Varadan Sevilimedu, Keisha D Pressley, Kassandra R Snook, Jamesa V Hogges, Maria D Politis, Jessica K Sexton, Carmen H Duke, Blake A Smith, Lena C Swander, Kelly K Baker, Manoj Gambhir, Isaac Chun-Hai Fung
BACKGROUND: Qualitative evidence suggests that inadequate water, sanitation and hygiene (WASH) may affect diarrheal and helminthic infection in women disproportionately. We systematically searched PubMed in June 2014 (updated 2016) and the WHO website, for relevant articles. METHODS: Articles dealing with the public health relevance of helminthic and diarrheal diseases, and highlighting the role of gender in WASH were included. Where possible, we carried out a meta-analysis...
January 22, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28115356/evolution-of-the-sterol-biosynthetic-pathway-of-pythium-insidiosum-and-related-oomycetes-contributes-to-antifungal-drug-resistance
#9
Tassanee Lerksuthirat, Areeporn Sangcakul, Tassanee Lohnoo, Wanta Yingyong, Thidarat Rujirawat, Theerapong Krajaejun
Pythiosis is a life-threatening infectious disease, caused by the oomycete Pythium insidiosum Direct exposure to P. insidiosum zoospores can initiate infections of the eye, limb, gastrointestinal tract, or skin/subcutaneous tissue. Treatments for pythiosis have mostly relied on surgery. Antifungal drugs are generally ineffective against P. insidiosum However, one patient with an invasive P. insidiosum infection recovered completely, following treatment with terbinafine and itraconazole. Additionally, the drug-target sterol biosynthetic enzymes have been identified in the oomycete Aphanomyces euteiches It remains an open question whether P...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28112573/persistence-of-coxsackievirus-b4-in-pancreatic-ductal-like-cells-results-in-cellular-and-viral-changes
#10
E K Alidjinou, I Engelmann, J Bossu, C Villenet, M Figeac, M B Romond, F Sané, D Hober
Introduction Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. Methods A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated...
January 23, 2017: Virulence
https://www.readbyqxmd.com/read/28108356/lipid-a-structural-modifications-in-extreme-conditions-and-identification-of-unique-modifying-enzymes-to-define-the-toll-like-receptor-4-structure-activity-relationship
#11
REVIEW
Alison J Scott, Benjamin L Oyler, David R Goodlett, Robert K Ernst
Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28106086/efficient-method-for-comprehensive-computation-of-agent-level-epidemic-dissemination-in-networks
#12
Gilberto M Nakamura, Ana Carolina P Monteiro, George C Cardoso, Alexandre S Martinez
Susceptible-infected (SI) and susceptible-infected-susceptible (SIS) are simple agent-based models often employed in epidemic studies. Both models describe the time evolution of infectious diseases in networks whose vertices are either susceptible (S) or infected (I) agents. Precise estimation for disease spreading is one of the major goals in epidemic studies but often restricted to heavy numerical simulations. Analytic methods using operatorial content are subject to the asymmetric eigenvalue problem, limiting the use of perturbative methods...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28099093/patients-with-infectious-endocarditis-and-drug-dependence-have-worse-clinical-outcomes-after-valvular-surgery
#13
Anthony Lemaire, Viktor Dombrovskiy, Siavash Saadat, George Batsides, Aziz Ghaly, Alan Spotnitz, Leonard Y Lee
BACKGROUND: Patients with infective endocarditis (IE) are at high risk for post-operative morbidity and death, which might be associated with drug abuse. The purpose of this study is to evaluate the impact of drug dependence on outcomes in patients who have IE and undergo valvular surgery (VS). PATIENTS AND METHODS: The Nationwide/National Inpatient Sample 2001-2012 was queried to select patients with IE who had elective VS using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes...
January 18, 2017: Surgical Infections
https://www.readbyqxmd.com/read/28096124/nutritional-considerations-for-healthy-aging-and-reduction-in-age-related-chronic-disease
#14
REVIEW
Julie Shlisky, David E Bloom, Amy R Beaudreault, Katherine L Tucker, Heather H Keller, Yvonne Freund-Levi, Roger A Fielding, Feon W Cheng, Gordon L Jensen, Dayong Wu, Simin N Meydani
A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28091706/microclimates-might-limit-indirect-spillover-of-the-bat-borne-zoonotic-hendra-virus
#15
Gerardo Martin, Rebecca J Webb, Carla Chen, Raina K Plowright, Lee F Skerratt
Infectious diseases are transmitted when susceptible hosts are exposed to pathogen particles that can replicate within them. Among factors that limit transmission, the environment is particularly important for indirectly transmitted parasites. To try and assess a pathogens' ability to be transmitted through the environment and mitigate risk, we need to quantify its decay where transmission occurs in space such as the microclimate harbouring the pathogen. Hendra virus, a Henipavirus from Australian Pteropid bats, spills-over to horses and humans, causing high mortality...
January 14, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28069866/trim-proteins-and-diseases
#16
REVIEW
Masashi Watanabe, Shigetsugu Hatakeyama
Ubiquitination is one of the posttranslational modifications that regulates a number of intracellular events including signal transduction, protein quality control, transcription, cell cycle, apoptosis and development. The ubiquitin system functions as a garbage machine to degrade target proteins and as a regulator for several signalling pathways. Biochemical reaction of ubiquitination requires several enzymes including E1, E2 and E3, and E3 ubiquitin ligases play roles as receptors for recognizing target proteins...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28066604/shifted-focus-of-bronchoalveolar-lavage-in-patients-with-suspected-thoracic-malignancy-an-analysis-of-224-patients
#17
Xin Zhang, Yukun Kuang, Yuan Zhang, Kai He, Noah Lechtzin, Mingying Zeng, Rex C Yung, Canmao Xie
BACKGROUND: Bronchoscopies are extensively adopted for diagnosing and staging thoracic malignancies, but studies are missing as how to keep the process streamlined and more efficient. To evaluate current role of bronchoalveolar lavage (BAL) for cancer and possible infection diagnosis when practicing comprehensive bronchoscopy for patients suspected with thoracic malignancy, and provide foundation for possible practice modification. METHODS: We retrospectively analyzed a prospectively kept database of immunocompetent patients undergoing bronchoscopy for suspected non-hematologic malignancies...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28057212/regulation-of-cellular-immune-responses-in-sepsis-by-histone-modifications
#18
W F Carson, S L Kunkel
Severe sepsis, septic shock, and related inflammatory syndromes are driven by the aberrant expression of proinflammatory mediators by immune cells. During the acute phase of sepsis, overexpression of chemokines and cytokines drives physiological stress leading to organ failure and mortality. Following recovery from sepsis, the immune system exhibits profound immunosuppression, evidenced by an inability to produce the same proinflammatory mediators that are required for normal responses to infectious microorganisms...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28036306/infections-with-biological-therapy-strategies-for-risk-minimization-in-tropical-and-developing-countries
#19
REVIEW
Carlos E Pérez-Díaz, Erika Uribe-Pardo, Omar-Javier Calixto, Álvaro A Faccini-Martínez, Alfonso J Rodriguez-Morales
In recent decades, biological therapy has enabled disease activity control and improved quality of life in patients with autoimmune diseases. These therapies that are involved in immune response modifications and change multiple immunological pathways induce an incremental risk for certain infectious diseases. Though there have been recent advances in risk assessment for biological therapy, there is a lack of data and recommendations for assessing risks in populations with high prevalence of infectious diseases, such as those located in tropical areas and developing countries...
December 30, 2016: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/28034743/discovery-of-host-targeted-covalent-inhibitors-of-dengue-virus
#20
Mélissanne de Wispelaere, Margot Carocci, Yanke Liang, Qingsong Liu, Eileen Sun, Michael L Vetter, Jinhua Wang, Nathanael S Gray, Priscilla L Yang
We report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of Flaviviruses and other viruses. We used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by QL-XII-47, that are active against dengue virus. We show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectious cycle, and thus significantly contributes to the potent antiviral activity of these compounds...
December 26, 2016: Antiviral Research
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