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https://www.readbyqxmd.com/read/29779485/tgn-1412-and-bia-2474-trials-with-tragic-end-lessons-learnt-to-make-clinical-trials-safer
#1
Rimple Jeet Kaur, Surjit Singh, Preeti Sidhu, Pramod Kumar Sharma
BACKGROUND: Globally, there have been tremendous efforts by regulatory authorities to make clinical trials safer by making stringent clinical trial regulations. Despite this, we witnessed several tragic events. TGN1412 and BIA 10-2474 phase I trials are infamous trails in which healthy volunteers either succumbed to severe adverse effects or faced irreversible impairments of the test drug. Such afflictions in clinical trials are not only turbulent to the image of pharmaceutical industry but it also conveys dispiriting message for clinical trial participants...
May 20, 2018: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/29756316/fine-particulate-matter-associated-mortality-burden-of-lung-cancer-in-hebei-province-china
#2
Yutong He, Zhaoyu Gao, Tiantian Guo, Feng Qu, Di Liang, Daojuan Li, Jin Shi, Baoen Shan
BACKGROUND: The association between fine particulate matter (PM2.5 ) and lung cancer (LC) mortality in China is limited. The Beijing-Tianjin-Hebei region is infamous for serious air pollution. Seven of the top 10 cities with the worst air quality are located in Hebei Province. Thus, we explored the effect of 10 years of PM2.5 on the LC mortality rate in Hebei Province. METHODS: We quantified associations between LC mortality and PM2.5 and estimated the LC mortality burden attributed to PM2...
May 14, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29707230/a-tad-pilus-promotes-the-establishment-and-resistance-of-vibrio-vulnificus-biofilms-to-mechanical-clearance
#3
Meng Pu, Dean Allistair Rowe-Magnus
Vibrio vulnificus is autochthonous to estuaries and warm coastal waters. Infection occurs via open wounds or ingestion, where its asymptomatic colonization of seafood, most infamously oysters, provides a gateway into the human food chain. Colonization begins with initial surface contact, which is often mediated by bacterial surface appendages called pili. Type IV Tad pili are widely distributed in the Vibrionaceae, but evidence for a physiological role for these structures is scant. The V. vulnificus genome codes for three distinct tad loci...
2018: NPJ Biofilms and Microbiomes
https://www.readbyqxmd.com/read/29705990/a-gentle-floriphilic-katydid-phaneroptera-brevis-can-help-with-pollination-of-bidens-pilosa
#4
Ming Kai Tan, Hugh Tiang Wah Tan
The orthopterans, comprised of the grasshoppers, crickets, and katydids, are often considered as infamous agricultural pests that eat and destroy crops. While orthopterans can provide mutualistic ecological services including seed dispersal (Duthie et al. 2006; Suetsugu 2018), they are rarely considered capable of pollination (Micheneau et al. 2010). There are, however, some orthopterans which preferentially feed on flowers. These floriphilic orthopterans include a Phaneropterinid katydid, Phaneroptera brevis (Serville, 1838) which can be found frequently among flowers in Southeast Asia (Tan et al...
April 29, 2018: Ecology
https://www.readbyqxmd.com/read/29705518/a-cautionary-note-on-the-mutation-frequency-in-microbial-research
#5
Qi Zheng
The mutation frequency, also known as the mutant frequency, is an unnormalized quantity, and its normalized counterpart is the mutation rate. Due to historical reasons, the mutation frequency has been a predominant yardstick of microbial mutability in the field of mutator identification. While the mean mutation frequency is infamously erratic, replacing it with the median mutation frequency is not an effective remedy. By encouraging investigators to substitute mutation rates for mutation frequencies in microbial research, this paper directs attention to substantial open problems such as false positive control and massive nonmutant cell death...
April 22, 2018: Mutation Research
https://www.readbyqxmd.com/read/29666287/the-blast-fungus-decoded-genomes-in-flux
#6
Thorsten Langner, Aleksandra Białas, Sophien Kamoun
Plant disease outbreaks caused by fungi are a chronic threat to global food security. A prime case is blast disease, which is caused by the ascomycete fungus Magnaporthe oryzae (syn. Pyricularia oryzae ), which is infamous as the most destructive disease of the staple crop rice. However, despite its Linnaean binomial name, M. oryzae is a multihost pathogen that infects more than 50 species of grasses. A timely study by P. Gladieux and colleagues (mBio 9:e01219-17, 2018, https://doi.org/10.1128/mBio.01219-17) reports the most extensive population genomic analysis of the blast fungus thus far...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29522735/from-a-iv-to-z-ikv-attacks-from-emerging-and-re-emerging-pathogens
#7
George F Gao
100 years after the infamous "Spanish flu" pandemic, the 2017-2018 flu season has been severe, with numerous infections worldwide. In between, there have been continuous, relentless attacks from (re-)emerging viruses. To fully understand viral pathogenesis and develop effective medical countermeasures, we must strengthen current surveillance and basic research efforts.
March 8, 2018: Cell
https://www.readbyqxmd.com/read/29507146/%C3%AE-secretase-bace1-promotes-surface-expression-and-function-of-kv3-4-at-hippocampal-mossy-fiber-synapses
#8
Stephanie Hartmann, Fang Zheng, Michele C Kyncl, Sandra Karch, Kerstin Voelkl, Benedikt Zott, Carla D'Avanzo, Selene Lomoio, Giuseppina Tesco, Doo Y Kim, Christian Alzheimer, Tobias Huth
The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is deemed a major culprit in Alzheimer's disease, but accumulating evidence indicates that there is more to the enzyme than driving the amyloidogenic processing of the amyloid precursor protein. For example, BACE1 has emerged as an important regulator of neuronal activity through proteolytic and, most unexpectedly, also through nonproteolytic interactions with several ion channels. Here, we identify and characterize the voltage-gated K+ channel 3.4 (Kv3...
April 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#9
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29311536/historical-origins-of-the-tuskegee-experiment-the-dilemma-of-public-health-in-the-united-states
#10
Jinbin Park
The Tuskegee Study of Untreated Syphilis in the Negro Male was an observational study on African-American males in Tuskegee, Alabama between 1932 and 1972. The U. S. Public Health Service ran this study on more than 300 people without notifying the participants about their disease nor treating them even after the introduction of penicillin. The study included recording the progress of disease and performing an autopsy on the deaths. This paper explores historical backgrounds enabled this infamous study, and discusses three driving forces behind the Tuskegee Study...
December 2017: Ŭi Sahak
https://www.readbyqxmd.com/read/29280759/phylogenetic-analysis-as-a-forensic-tool-in-hiv-transmission-investigations
#11
Ana B Abecasis, Marta Pingarilho, Anne-Mieke Vandamme
: Because HIV is a fast-evolving virus, HIV genomic sequences of several individuals can be used to investigate whether they belong to a transmission network. Since the infamous 'Florida dentist case' in the beginning of the 1990s, phylogenetic analyses has been recurrently used in court settings as a forensic tool in HIV transmission investigations, for example cases where one or more complainants allege that a defendant has unlawfully infected them with HIV. Such cases can arise both in the context of HIV-specific criminal laws - in countries where transmission of HIV infection is specifically criminalized - or in the context of general laws, for example, by applying physical or sexual assault laws to HIV-related cases...
March 13, 2018: AIDS
https://www.readbyqxmd.com/read/29235706/a-conserved-tad-pilus-promotes-vibrio-vulnificus-oyster-colonization
#12
Meng Pu, Patrick Duriez, Mattan Arazi, Dean A Rowe-Magnus
Vibrio vulnificus has the highest death rate (>35%) and per-case economic burden ($3.3 million) of any foodborne pathogen in the United States. Infections occur via open wounds or following ingestion of contaminated seafood, most infamously oysters. We isolated a 1000th generation descendant, designated NT that exhibited increased biofilm and aggregate formation relative to its parent. We identified two significant causal changes underlying these phenotypes. First, the entire 24-kb capsular polysaccharide biosynthesis locus, which is essential for virulence but inhibits biofilm formation, had been purged from the genome...
February 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29177504/pathogenomic-analysis-of-wheat-yellow-rust-lineages-detects-seasonal-variation-and-host-specificity
#13
Vanessa Bueno-Sancho, Antoine Persoons, Amelia Hubbard, Luis Enrique Cabrera-Quio, Clare M Lewis, Pilar Corredor-Moreno, Daniel C E Bunting, Sajid Ali, Soonie Chng, David P Hodson, Ricardo Madariaga Burrows, Rosie Bryson, Jane Thomas, Sarah Holdgate, Diane G O Saunders
Recent disease outbreaks caused by (re-)emerging plant pathogens have been associated with expansions in pathogen geographic distribution and increased virulence. For example, in the past two decades' wheat yellow (stripe) rust, Puccinia striiformis f. sp. tritici, has seen the emergence of new races that are adapted to warmer temperatures, have expanded virulence profiles, and are more aggressive than previous races, leading to wide-scale epidemics. Here, we used field-based genotyping to generate high-resolution data on P...
December 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29155148/functional-properties-and-mechanism-of-action-of-pptq-an-allosteric-agonist-and-low-nanomolar-positive-allosteric-modulator-at-gaba-a-receptors
#14
Nawid Madjroh, Emma Rie Olander, Christoffer Bundgaard, Pella Cecilia Söderhielm, Anders A Jensen
The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABAA receptors (GABAA Rs) (Hammer et al., 2015). In the present study, we have identified a novel methaqualone analog, 2-phenyl-3-(p-tolyl)quinazolin-4(3H)-one (PPTQ), in a screening of 67 analogs at five αβ2 γ2S GABAA R subtypes and delineated its functional properties and mechanism of action at wild-type and mutant GABAA Rs expressed in Xenopus laevis oocytes by two-electrode voltage clamp electrophysiology...
January 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29074260/rattling-the-border-wall-pathophysiological-implications-of-functional-and-proteomic-venom-variation-between-mexican-and-us-subspecies-of-the-desert-rattlesnake-crotalus-scutulatus
#15
James Dobson, Daryl C Yang, Bianca Op den Brouw, Chip Cochran, Tam Huynh, Sanjaya Kurrupu, Elda E Sánchez, Daniel J Massey, Kate Baumann, Timothy N W Jackson, Amanda Nouwens, Peter Josh, Edgar Neri-Castro, Alejandro Alagón, Wayne C Hodgson, Bryan G Fry
While some US populations of the Mohave rattlesnake (Crotalus scutulatus scutulatus) are infamous for being potently neurotoxic, the Mexican subspecies C. s. salvini (Huamantlan rattlesnake) has been largely unstudied beyond crude lethality testing upon mice. In this study we show that at least some populations of this snake are as potently neurotoxic as its northern cousin. Testing of the Mexican antivenom Antivipmyn showed a complete lack of neutralisation for the neurotoxic effects of C. s. salvini venom, while the neurotoxic effects of the US subspecies C...
February 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29063276/the-infamous-famous-sulfonylureas-and-cardiovascular-safety-much-ado-about-nothing
#16
REVIEW
Laurentiu M Pop, Ildiko Lingvay
PURPOSE OF REVIEW: Sulfonylureas (SUs) are one of the most commonly used glucose-lowering agents worldwide. While their efficacy is undisputed, their cardiovascular safety has been debated since the 1970's. RECENT FINDINGS: With no dedicated cardiovascular studies to definitively answer this question, observational studies and meta-analyses abound and have reported divergent results, fueling the controversy. Studies that compared SUs to metformin or newer agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in cardiovascular events, yet this is likely the result of beneficial effects of the latter...
October 23, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28855209/therapeutic-targeting-of-oncogenic-tyrosine-phosphatases
#17
REVIEW
Rochelle Frankson, Zhi-Hong Yu, Yunpeng Bai, Qinglin Li, Ruo-Yu Zhang, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28769045/arsenic-exposure-impels-cd4-commitment-in-thymus-and-suppress-t-cell-cytokine-secretion-by-increasing-regulatory-t-cells
#18
Ruchi Gera, Vikas Singh, Sumonto Mitra, Anuj Kumar Sharma, Alok Singh, Arunava Dasgupta, Dhirendra Singh, Mahadeo Kumar, Pankaj Jagdale, Satyakam Patnaik, Debabrata Ghosh
Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751210/melamine-beyond-the-kidney-a-ubiquitous-endocrine-disruptor-and-neurotoxicant
#19
REVIEW
Ashley L Bolden, Johanna R Rochester, Carol F Kwiatkowski
Melamine is commonly used in a variety of consumer products such as furniture, dining ware, and food utensils. The chemical infamously gained worldwide attention by its illegal addition to a variety of foodstuffs in order to falsify protein content, which led to serious, sometimes fatal, health impacts in children and pets. This resulted in a large amount of published primary studies and reviews of the impacts of melamine exposure on kidney function. However, a growing body of literature suggests that melamine may have impacts beyond renal dysfunction...
October 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28746410/environmental-factors-influencing-the-spatio-temporal-distribution-of-carybdea-marsupialis-lineo-1978-cubozoa-in-south-western-mediterranean-coasts
#20
Antonio Canepa, Verónica Fuentes, Mar Bosch-Belmar, Melissa Acevedo, Kilian Toledo-Guedes, Antonio Ortiz, Elia Durá, César Bordehore, Josep-Maria Gili
Jellyfish blooms cause important ecological and socio-economic problems. Among jellyfish, cubozoans are infamous for their painful, sometimes deadly, stings and are a major public concern in tropical to subtropical areas; however, there is little information about the possible causes of their outbreaks. After a bloom of the cubomedusa Carybdea marsupialis (Carybdeidae) along the coast of Denia (SW Mediterranean, Spain) in 2008 with negative consequences for local tourism, the necessity to understand the ecological restrictions on medusae abundance was evident...
2017: PloS One
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