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https://www.readbyqxmd.com/read/29067346/phase-ii-clinical-trials-of-anti-amyloid-%C3%AE-antibodies-when-is-enough-enough
#1
REVIEW
Michael Gold
Efforts to develop new therapies to combat Alzheimer's disease suffer from extraordinarily high failure rates that make it difficult to justify continued investment in the field. Although there are a number of plausible explanations for this extremely high attrition rate, one of the explanations that has received little attention is the lack of compelling data from Phase II studies for compounds that have been pushed into Phase III trials and then have failed. An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials...
September 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29019704/fair-is-fair-preventing-the-misuse-of-visiting-hours-to-reduce-inequities
#2
Giora Netzer, Theodore J Iwashyna
While family is an essential unit of every society on earth, many intensive care units (ICUs) continue to impose limitations on families' access to their loved ones. Unlimited family presence is backed both by data and multiple professional societies' guidelines. We propose that the obligation to protect the integrity and needs of our patients and families extends past our immediate relationship to them at the bedside, and is also a societal imperative. In a society rife with implicit bias, restrictions on family visitation risk selective enforcement of these rules, and further propagates social injustice...
October 11, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28933884/critical-action-as-a-pathway-to-social-mobility-among-marginalized-youth
#3
Luke J Rapa, Matthew A Diemer, Josefina Bañales
Marginalized youth's development occurs in contexts rife with racialized, gendered, and socioeconomic social identity threats and barriers to social mobility. An emergent line of inquiry suggests critical action-a component of critical consciousness, defined as engaging in individual or collective social action to produce social change-may bolster career development for those experiencing marginalization. Yet, the specific mechanisms underlying critical action-career development associations are not well understood...
September 21, 2017: Developmental Psychology
https://www.readbyqxmd.com/read/28931681/insights-into-the-impact-of-cd8-immune-modulation-on-hiv-evolutionary-dynamics-in-distinct-anatomical-compartments-using-siv-infected-macaque-models-of-aids-progression
#4
Brittany Rife Magalis, David J Nolan, Patrick Autissier, Tricia H Burdo, Kenneth C Williams, Marco Salemi
A thorough understanding of the role of HIV intra-host evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8+ lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to similar clinical manifestations as HIV-1 infection and AIDS progression, as well as characteristic rapid disease onset...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28864654/exogenous-polyunsaturated-fatty-acids-impact-membrane-remodeling-and-affect-virulence-phenotypes-among-pathogenic-vibrio-species
#5
Anna R Moravec, Andrew W Siv, Chelsea R Hobby, Emily N Lindsay, Layla V Norbash, Daniel J Shults, Steven J K Symes, David K Giles
The pathogenic Vibrio species (V. cholerae, V. parahaemolyticus, and V. vulnificus) represent a constant threat to human health, causing foodborne and skin wound infections as a result of ingestion of or exposure to contaminated water and seafood. Recent studies have highlighted Vibrio's ability to acquire fatty acids from environmental sources and assimilate them into cell membranes. The possession and conservation of such machinery provokes consideration of fatty acids as important factors in the pathogenic lifestyle of Vibrio species...
November 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28825527/a-grounded-theory-of-sexual-minority-women-and-transgender-individuals-social-justice-activism
#6
Whitney B Hagen, Stephanie M Hoover, Susan L Morrow
Psychosocial benefits of activism include increased empowerment, social connectedness, and resilience. Yet sexual minority women (SMW) and transgender individuals with multiple oppressed statuses and identities are especially prone to oppression-based experiences, even within minority activist communities. This study sought to develop an empirical model to explain the diverse meanings of social justice activism situated in SMW and transgender individuals' social identities, values, and experiences of oppression and privilege...
August 21, 2017: Journal of Homosexuality
https://www.readbyqxmd.com/read/28821712/emergence-of-recombinant-mayaro-virus-strains-from-the-amazon-basin
#7
Carla Mavian, Brittany D Rife, James Jarad Dollar, Eleonora Cella, Massimo Ciccozzi, Mattia C F Prosperi, John Lednicky, J Glenn Morris, Ilaria Capua, Marco Salemi
Mayaro virus (MAYV), causative agent of Mayaro Fever, is an arbovirus transmitted by Haemagogus mosquitoes. Despite recent attention due to the identification of several cases in South and Central America and the Caribbean, limited information on MAYV evolution and epidemiology exists and represents a barrier to prevention of further spread. We present a thorough spatiotemporal evolutionary study of MAYV full-genome sequences collected over the last sixty years within South America and Haiti, revealing recent recombination events and adaptation to a broad host and vector range, including Aedes mosquito species...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809850/function-related-replacement-of-bacterial-siderophore-pathways
#8
Hilke Bruns, Max Crüsemann, Anne-Catrin Letzel, Mohammad Alanjary, James O McInerney, Paul R Jensen, Stefan Schulz, Bradley S Moore, Nadine Ziemert
Bacterial genomes are rife with orphan biosynthetic gene clusters (BGCs) associated with secondary metabolism of unrealized natural product molecules. Often up to a tenth of the genome is predicted to code for the biosynthesis of diverse metabolites with mostly unknown structures and functions. This phenomenal diversity of BGCs coupled with their high rates of horizontal transfer raise questions about whether they are really active and beneficial, whether they are neutral and confer no advantage, or whether they are carried in genomes because they are parasitic or addictive...
August 15, 2017: ISME Journal
https://www.readbyqxmd.com/read/28796277/talking-the-talk-but-not-walking-the-walk-rt-qpcr-as-a-paradigm-for-the-lack-of-reproducibility-in-molecular-research
#9
REVIEW
Stephen Bustin, Tania Nolan
Poorly executed and inadequately reported molecular measurement methods are amongst the causes underlying the lack of reproducibility of much biomedical research. Although several high impact factor journals have acknowledged their past failure to scrutinise adequately the technical soundness of manuscripts, there is a perplexing reluctance to implement basic corrective measures. The reverse transcription real-time quantitative PCR (RT-qPCR) is probably the most straightforward measurement technique available for RNA quantification and is widely used in research, diagnostic, forensic and biotechnology applications...
August 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28761006/unpacking-the-species-conundrum-philosophy-practice-and-a-way-forward
#10
Kartik Shanker, S P Vijayakumar, K N Ganeshaiah
The history of ecology and evolutionary biology is rife with attempts to define and delimit species. However, there has been confusion between concepts and criteria, which has led to discussion, debate, and conflict, eventually leading to lack of consistency in delimitation. Here, we provide a broad review of species concepts, a clarification of category versus concept, an account of the general lineage concept (GLC), and finally a way forward for species discovery and delimitation. Historically, species were considered as varieties bound together by reproduction...
July 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28654659/environmental-change-drives-accelerated-adaptation-through-stimulated-copy-number-variation
#11
Ryan M Hull, Cristina Cruz, Carmen V Jack, Jonathan Houseley
Copy number variation (CNV) is rife in eukaryotic genomes and has been implicated in many human disorders, particularly cancer, in which CNV promotes both tumorigenesis and chemotherapy resistance. CNVs are considered random mutations but often arise through replication defects; transcription can interfere with replication fork progression and stability, leading to increased mutation rates at highly transcribed loci. Here we investigate whether inducible promoters can stimulate CNV to yield reproducible, environment-specific genetic changes...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#12
REVIEW
Paul J Baker, Dominic De Nardo, Fiona Moghaddas, Le Son Tran, Annabell Bachem, Tan Nguyen, Thomas Hayman, Hazel Tye, James E Vince, Sammy Bedoui, Richard L Ferrero, Seth L Masters
Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28609580/metabolic-defence-against-oxidative-stress-the-road-less-travelled-so-far
#13
REVIEW
J Lemire, A Alhasawi, V P Appanna, S Tharmalingam, V D Appanna
Bacteria have survived, and many have thrived, since antiquity in the presence of the highly-reactive chalcogen-oxygen (O2 ). They are known to evoke intricate strategies to defend themselves from the reactive by-products of oxygen-reactive oxygen species (ROS). Many of these detoxifying mechanisms have been extensively characterized; superoxide dismutase, catalases, alkyl hydroperoxide reductase and the glutathione (GSH)-cycling system are responsible for neutralizing specific ROS. Meanwhile, a pool of NADPH-the reductive engine of many ROS-combating enzymes-is maintained by metabolic enzymes including, but not exclusively, glucose-6 phosphate dehydrogenase (G6PDH) and NADP-dependent isocitrate dehydrogenase (ICDH-NADP)...
June 13, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28576578/understanding-solid-phase-hla-antibody-assays-and-the-value-of-mfi
#14
REVIEW
Harold C Sullivan, Howard M Gebel, Robert A Bray
As the practice of medicine becomes more reliant on imaging and laboratory tests, medical decisions will be increasingly based on numbers. Accordingly, following the introduction of solid-phase testing to the HLA testing repertoire, laboratory directors and physicians have employed preset mean fluorescence intensity (MFI) thresholds as the basis for decisions in the management of transplant patients. However, what do MFI values mean? The literature is rife with reports detailing numerous factors that influence antibody assessment including (but not limited to) sensitization history of the patient, level of mismatch between donor and recipient, presence of interfering substances in the serum, whether the antigen on multiplex beads is native or denatured, day-to-day and technologist variability, and the historical performance of an assay in a given institution...
May 30, 2017: Human Immunology
https://www.readbyqxmd.com/read/28501896/what-do-biologists-make-of-the-species-problem
#15
Bruno Pušić, Pavel Gregorić, Damjan Franjević
The concept of species is one of the core concepts in biology and one of the cornerstones of evolutionary biology, yet it is rife with conceptual problems. Philosophers of biology have been discussing the concept of species for decades, and in doing so they sometimes appeal to the views of biologists. However, their statements as to what biologists think are seldom supported by empirical data. In order to investigate what biologists actually think about the key issues related to the problem of species, we have conducted a survey on the sample of 193 biologists from the population of biologists from over 150 biology departments at universities in the US and the EU...
May 13, 2017: Acta Biotheoretica
https://www.readbyqxmd.com/read/28438256/clinical-profile-and-outcome-of-patients-with-biopsy-proven-acute-interstitial-nephritis-in-cape-town-a-10-year-review%C3%A2
#16
Emmanuel E Effa, Udeme E Ekrikpo, Megan Borkum, Brian L Rayner, Peter Heering, Ikechi G Okpechi
BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney injury that has not been adequately characterized in Sub-Saharan Africa (SSA) despite an increasing use of potentially inciting agents for the treatment of human immunodeficiency virus (HIV) and tuberculosis in the region. METHODS: A retrospective audit of records of patients with biopsy-proven AIN diagnosed at Groote Schuur Hospital, Cape Town from the 1st of January, 2006, to the 31st of December, 2015...
April 25, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28421932/learning-disability-nurse-numbers-heading-in-the-wrong-direction
#17
(no author information available yet)
The UK's record on supporting people with learning disabilities is patchy to say the least. For decades people were housed in inappropriate institutions where abuse was rife, and attempts to improve their lives by delivering better services in the community have come up short because they have not been afforded sufficient priority.
April 19, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28419609/band-aids-for-buchnera-and-b-vitamins-for-all
#18
Jacob A Russell, Kerry M Oliver, Allison K Hansen
Evolution lacks foresight, and hence, key adaptations may produce major challenges over the long run. The natural world is rife with examples of long-term 'side effects' associated with quick-fix tinkering, including blind spots in vertebrate eyes. An important question is how nature compensates for imperfections once evolution has set a course. The symbioses associated with sap-feeding insects present a fascinating opportunity to address this issue. On one hand, the substantial diversity and biomass of sap-feeding insects are largely due to ancient acquisitions of nutrient-provisioning bacterial symbionts...
April 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28400787/silicification-in-grasses-variation-between-different-cell-types
#19
REVIEW
Santosh Kumar, Milan Soukup, Rivka Elbaum
Plants take up silicon as mono-silicic acid, which is released to soil by the weathering of silicate minerals. Silicic acid can be taken up by plant roots passively or actively, and later it is deposited in its polymerized form as amorphous hydrated silica. Major silica depositions in grasses occur in root endodermis, leaf epidermal cells, and outer epidermal cells of inflorescence bracts. Debates are rife about the mechanism of silica deposition, and two contrasting scenarios are often proposed to explain it...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28366126/prescriptions-filled-following-an-opioid-related-hospitalization
#20
Ellen Herbst, Tauheed Zaman, Tessa Rife
No abstract text is available yet for this article.
April 1, 2017: Psychiatric Services: a Journal of the American Psychiatric Association
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