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https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#1
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28566076/-evaluation-of-viral-etiology-in-central-nervous-system-infections-from-a-university-hospital-point-of-view-in-izmir-based-on-seven-years-data
#2
Ayşın Zeytinoğlu, Selda Erensoy, Rüçhan Sertöz, İmre Altuğlu, Candan Çiçek, Münevver Kayın, Hadiye Şirin, Şafak Taner
The serious diseases of the central nervous system (CNS); encephalitis and meningitis, have high mortality and morbidity rate especially not diagnosed and treated in time. Nucleic acid testing (NAT) is the tool of choice for viral diagnosis in CNS infections. In this study, viral etiological agents found in cerebrospinal fluid (CSF) samples sent to our university hospital virology laboratory for laboratory diagnosis of CNS infections were retrospectively evaluated and results were compared with other reports from our country...
April 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28560543/bone-and-soft-tissue-histology-a-new-approach-to-determine-characteristics-of-offending-instrument-in-sharp-force-injuries
#3
Tania Delabarde, Catherine Cannet, Jean Sébastien Raul, Annie Géraut, Marc Taccoen, Bertrand Ludes
This paper describes a new approach to determine characteristics of the implement used to inflict trauma which involves the histological analysis of exogenous particles. Based on Locard's principle "every contact leaves a trace," we decided to assess whether histological examination of bone and soft tissue around a penetrating injury (sharp force trauma) could provide evidence of the offending implement. Case reports and experimental studies have demonstrated the potential of cut mark features in bone to identify the causative implement and potentially assist in identifying the perpetrator...
May 30, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28549597/prolactin-receptor-targeting-in-breast-and-prostate-cancers-new-insights-into-an-old-challenge
#4
REVIEW
Vincent Goffin
In the era of precision medicine, the identification of new targets is a constant challenge to improve cancer therapy. Preclinical investigations, epidemiological studies and analyses of tissue specimens from patients strongly support the contribution of prolactin receptor (PRLR) signaling to breast and prostate tumorigenesis and cancer progression. Although a clear causative link with mutations of the genes encoding prolactin or its receptor is lacking, increased PRLR signaling in these cancers can be assessed by the overexpression of cognate proteins and is often confirmed by over-activation of downstream signaling effectors...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28539839/ppard-is-an-inhibitor-of-cartilage-growth-in-external-ears
#5
Zhen Zhang, Yanyu Duan, Zhongping Wu, Hui Zhang, Jun Ren, Lusheng Huang
Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28536827/genetic-counselling-for-maternally-inherited-mitochondrial-disorders
#6
REVIEW
Joanna Poulton, Josef Finsterer, Patrick Yu-Wai-Man
The aim of this review was to provide an evidence-based approach to frequently asked questions relating to the risk of transmitting a maternally inherited mitochondrial disorder (MID). We do not address disorders linked with disturbed mitochondrial DNA (mtDNA) maintenance, causing mtDNA depletion or multiple mtDNA deletions, as these are autosomally inherited. The review addresses questions regarding prognosis, recurrence risks and the strategies available to prevent disease transmission. The clinical and genetic complexity of maternally inherited MIDs represent a major challenge for patients, their relatives and health professionals...
May 23, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28526628/heparin-based-hydrogels-induce-human-renal-tubulogenesis-in-vitro
#7
Heather M Weber, Mikhail V Tsurkan, Valentina Magno, Uwe Freudenberg, Carsten Werner
Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28518168/using-high-resolution-variant-frequencies-to-empower-clinical-genome-interpretation
#8
Nicola Whiffin, Eric Minikel, Roddy Walsh, Anne H O'Donnell-Luria, Konrad Karczewski, Alexander Y Ing, Paul J R Barton, Birgit Funke, Stuart A Cook, Daniel MacArthur, James S Ware
PurposeWhole-exome and whole-genome sequencing have transformed the discovery of genetic variants that cause human Mendelian disease, but discriminating pathogenic from benign variants remains a daunting challenge. Rarity is recognized as a necessary, although not sufficient, criterion for pathogenicity, but frequency cutoffs used in Mendelian analysis are often arbitrary and overly lenient. Recent very large reference datasets, such as the Exome Aggregation Consortium (ExAC), provide an unprecedented opportunity to obtain robust frequency estimates even for very rare variants...
May 18, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28505618/use-of-epinephrine-in-patients-with-drug-induced-anaphylaxis-an-analysis-of-the-beijing-pharmacovigilance-database
#9
Tiansheng Wang, Xiang Ma, Yan Xing, Shusen Sun, Hua Zhang, Til Stürmer, Bin Wang, Xiaotong Li, Huilin Tang, Ligong Jiao, Suodi Zhai
BACKGROUND: Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. METHODS: DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28504347/a-rapid-method-to-screen-poisoning-causative-agents-in-an-acute-care-hospital-in-japan
#10
K Usui, H Mori, T Tachi, T Matsumura, K Mori, A Takeda, Y Noguchi, T Yoshimura, H Teramachi
WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to simultaneously analyse medicinal toxicants in emergency medical care. In this regard, the analysis of blood samples by LC-MS/MS equipped with a spin column, involving a rapid, simple pretreatment, has attracted attention. In this study, sample pretreatment using a Monospin C18 column was performed to screen 11 medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam, diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone, fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis...
May 15, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28493060/synthetic-turf-fields-crumb-rubber-and-alleged-cancer-risk
#11
Archie Bleyer
Most synthetic turf fields have crumb rubber interspersed among the simulated grass fibers to reduce athletic injuries by allowing users to turn and slide more readily as they play sports or exercise on the fields. Recently, the crumbs have been implicated in causing cancer in adolescents and young adults who use the fields, particularly lymphoma and primarily in soccer goalkeepers. This concern has led to the initiation of large-scale studies by local and federal governments that are expected to take years to complete...
May 11, 2017: Sports Medicine
https://www.readbyqxmd.com/read/28485358/opium-consumption-a-potential-risk-factor-for-lung-cancer-and-pulmonary-tuberculosis
#12
A Safari, M Reazai, A Tangestaninejad, A R Mafi, Saj Mousavi
OBJECTIVE: Lung cancer is the most common malignancy, as well as the leading cause of cancer-related mortality worldwide. Several studies have shown the causative effect of cigarettes smoking in lung cancer, however, the effect of opium consumption has not yet been well studied. This study has been designed to evaluate the risk of developing lung cancer and pulmonary tuberculosis in pure opium addicts. MATERIALS AND METHODS: We designed an analytic case-control study with 490 participants...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28481730/next-generation-sequencing-reveals-novel-mutations-in-x-linked-intellectual-disability
#13
Babylakshmi Muthusamy, Lakshmi Dhevi N Selvan, Thong T Nguyen, Jesna Manoj, Eric W Stawiski, Bijay S Jaiswal, Weiru Wang, Remya Raja, Vedam Laxmi Ramprasad, Ravi Gupta, Sakthivel Murugan, Jayarama S Kadandale, T S Keshava Prasad, Kavita Reddy, Andrew Peterson, Akhilesh Pandey, Somasekar Seshagiri, Satish Chandra Girimaji, Harsha Gowda
Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is associated with a range of phenotypes impacting societies in both developed and developing countries. Although intellectual disability arises due to diverse causes, a substantial proportion is caused by genomic alterations...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28481398/evolutionary-trade-offs-in-kidney-injury-and-repair
#14
REVIEW
Yutian Lei, Hans-Joachim Anders
Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease...
May 8, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28472444/factors-related-to-medical-students-and-doctors-attitudes-towards-older-patients-a-systematic-review
#15
Rajvinder Samra, Tom Cox, Adam Lee Gordon, Simon Paul Conroy, Mathijs F G Lucassen, Amanda Griffiths
Background: studies have sought to identify the possible determinants of medical students' and doctors' attitudes towards older patients by examining relationships with a variety of factors: demographic, educational/training, exposure to older people, personality/cognitive and job/career factors. This review collates and synthesises these findings. Methods: an electronic search of 10 databases was performed (ABI/Inform, ASSIA, British Nursing Index, CINAHL, Informa Health, Medline, PsycINFO, Science Direct, Scopus, and Web of Science) through to 7 February 2017...
May 2, 2017: Age and Ageing
https://www.readbyqxmd.com/read/28454485/cheminformatics-based-anticoagulant-study-of-traditionally-used-medicinal-plants
#16
Mahdi Alikhani Pour, Soroush Sardari, Ali Eslamifar, Abid Azhar, Mohammad Rezvani, Milad Nazari
Backgroung: Medicinal plants, as a complementary medicine, have been used to treat various diseases since ancient times. These plants have numerous beneficial applications and are the source of certain conventional drugs. In diseases such as stroke and ischemia, which are caused by several factors, abnormal coagulation is an important causative factor. Accordingly, novel and effective therapies such as herbal remedies should be practiced to prevent such lethal diseases. Methods: Using the available databases such as Google Scholar and PubMed, the previously reported anticoagulant compounds and plants possessing anticoagulant activity were identified and collected in two separate lists...
April 29, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28453775/deconvoluting-kinase-inhibitor-induced-cardiotoxicity
#17
Sarah D Lamore, Ernst Ahlberg, Scott Boyer, Michelle L Lamb, Maria P Hortigon-Vinagre, Victor Rodriguez, Godfrey L Smith, Johanna Sagemark, Lars Carlsson, Stephanie M Bates, Allison L Choy, Jonna Stålring, Clay W Scott, Matthew F Peters
Many drugs designed to inhibit kinases have their clinical utility limited by cardiotoxicity-related label warnings or prescribing restrictions. While this liability is widely recognized, designing safer kinase inhibitors (KI) requires knowledge of the causative kinase(s). Efforts to unravel the kinases have encountered pharmacology with nearly prohibitive complexity. At therapeutically relevant concentrations, KIs show promiscuity distributed across the kinome. Here, to overcome this complexity, 65 KIs with known kinome-scale polypharmacology profiles were assessed for effects on cardiomyocyte beating...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28445563/outbreak-of-occupational-dermatitis-associated-with-pyemotes-ventricosus
#18
Martyna Tomczyk-Socha, Katarzyna Jedrzejewska-Jurga, Joanna Limburska, Jaroslaw Tomczyk
Importance: Although Pyemotes spp have been known to cause dermatitis, recent reports are rare. During the past 30 years, only 3 outbreaks of dermatitis caused by Pyemotes ventricosus have been reported. Objective: To analyze the causative agent of skin changes in employees of a company that produced herbal medicines. Design, Setting, and Participants: This case series includes 18 patients (8 men, 10 women; mean age, 44 years) who contracted unusual dermatitis after an occupational exposure in July and August of 2012 while working for a company that produced herbal medicines...
April 26, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28432381/modulation-of-the-multidrug-efflux-pump-emrd-3-from-vibrio-cholerae-by-allium-sativum-extract-and-the-bioactive-agent-allyl-sulfide-plus-synergistic-enhancement-of-antimicrobial-susceptibility-by-a-sativum-extract
#19
Merissa M Bruns, Prathusha Kakarla, Jared T Floyd, Mun Mun Mukherjee, Robert C Ponce, John A Garcia, Indrika Ranaweera, Leslie M Sanford, Alberto J Hernandez, T Mark Willmon, Grace L Tolson, Manuel F Varela
The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux...
April 21, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#20
Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease...
2017: Advances in Protein Chemistry and Structural Biology
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