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Expedition medicine

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https://www.readbyqxmd.com/read/28435537/integrated-platform-for-expedited-synthesis-purification-testing-of-small-molecule-libraries
#1
Aleksandra Baranczak, Noah P Tu, Jasmina Marjanovic, Philip A Searle, Anil Vasudevan, Stevan W Djuric
The productivity of medicinal chemistry programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, we describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small molecule libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28411938/medicolegal-issues-in-expedition-and-wilderness-medicine
#2
REVIEW
Valerie A Dobiesz, William Sullivan
There is increased participation in wilderness expeditions to remote and austere environments, which increases the likelihood of an accident and/or medical emergency and the professional liability risks for trip organizers. Trip organizers, outfitters, tour guides, and health care providers must understand the medicolegal liabilities involved in and the legal protection and immunity available when rendering care in austere and challenging settings to mitigate risks and prepare for the level of medical care that may be required...
May 2017: Emergency Medicine Clinics of North America
https://www.readbyqxmd.com/read/28399929/xanthogranulomatous-pyelonephritis-presenting-as-acute-pleuritic-chest-pain-a-case-report
#3
Justin Chow, Rameez Kabani, Kirstie Lithgow, Magdalena A Sarna
BACKGROUND: Xanthogranulomatous pyelonephritis is a rare and serious manifestation of chronic kidney inflammation that can be life-threatening if not recognized and treated appropriately, often with antibiotics and surgery. Affected patients are most commonly females in their fifth or sixth decade of life with a background of obstructive uropathy, nephrolithiasis, or recurrent urinary tract infections who present with vague nonspecific symptoms. CASE PRESENTATION: A 43-year-old woman of Russian ethnicity with a history of nephrolithiasis presented to our emergency department with new left-sided pleuritic chest pain amid a 6-week history of constitutional symptoms including fevers, night sweats, and 7 kg of weight loss...
April 12, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28392910/drug-shortages-in-israel-regulatory-perspectives-challenges-and-solutions
#4
Eyal Schwartzberg, Denize Ainbinder, Alla Vishkauzan, Ronni Gamzu
BACKGROUND: Pharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients' wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013-2015, assessing their etiology and exploring the steps taken for their mitigation and prevention...
2017: Israel Journal of Health Policy Research
https://www.readbyqxmd.com/read/28356122/integrated-analysis-identifies-microrna-195-as-a-suppressor-of-hippo-yap-pathway-in-colorectal-cancer
#5
Min Sun, Haibin Song, Shuyi Wang, Chunxiao Zhang, Liang Zheng, Fangfang Chen, Dongdong Shi, Yuanyuan Chen, Chaogang Yang, Zhenxian Xiang, Qing Liu, Chen Wei, Bin Xiong
BACKGROUND: With persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a "pre-laboratory" integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear. METHODS: In this study, we performed an integrated analysis of seven CRC miRNAs expression datasets...
March 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28349986/spatial-transcriptome-analysis-provides-insights-of-key-gene-s-involved-in-steroidal-saponin-biosynthesis-in-medicinally-important-herb-trillium-govanianum
#6
Pradeep Singh, Gagandeep Singh, Abhishek Bhandawat, Gopal Singh, Rajni Parmar, Romit Seth, Ram Kumar Sharma
Trillium govanianum, an endangered medicinal herb native to the Himalaya, is less studied at the molecular level due to the non-availability of genomic resources. To facilitate the basic understanding of the key genes and regulatory mechanism of pharmaceutically important biosynthesis pathways, first spatial transcriptome sequencing of T. govanianum was performed. 151,622,376 (~11.5 Gb) high quality reads obtained using paired-end Illumina sequencing were de novo assembled into 69,174 transcripts. Functional annotation with multiple public databases identified array of genes involved in steroidal saponin biosynthesis and other secondary metabolite pathways including brassinosteroid, carotenoid, diterpenoid, flavonoid, phenylpropanoid, steroid and terpenoid backbone biosynthesis, and important TF families (bHLH, MYB related, NAC, FAR1, bZIP, B3 and WRKY)...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295709/ring-expansion-reactions-in-the-synthesis-of-macrocycles-and-medium-sized-rings
#7
James Robert Donald, William Paul Unsworth
Functionalised macrocycles and medium-sized rings have applications in a number of scientific fields, ranging from medicinal chemistry and supramolecular chemistry, to catalysis and nanotechnology. However, their value in these areas can be undermined by a simple, but important limitation: large ring systems are very often difficult to make. Traditional end-to-end cyclisation reactions of long linear precursors are typically unpredictable and impractical processes, mainly due to unfavourable enthalpic and entropic factors...
March 15, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28280722/tissue-engineered-solutions-in-plastic-and-reconstructive-surgery-principles-and-practice
#8
REVIEW
Sarah Al-Himdani, Zita M Jessop, Ayesha Al-Sabah, Emman Combellack, Amel Ibrahim, Shareen H Doak, Andrew M Hart, Charles W Archer, Catherine A Thornton, Iain S Whitaker
Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28271897/branched-chain-amino-acids-as-predictors-for-individual-differences-of-cisplatin-nephrotoxicity-in-rats-a-pharmacometabonomics-study
#9
Pei Zhang, Wei Li, Jiaqing Chen, Ruiting Li, Zunjian Zhang, Yin Huang, Fengguo Xu
Nephrotoxicity is the dose-limiting adverse effect of cisplatin with large individual differences. Up to now, little has been done on how to recognize and predict the individual differences in either preclinical or clinical research. In the present study, important postdose indicators were screened out first and integrated into a grouping factor, according to which rats were recognized as lowly or highly sensitive individuals. Then, mass-spectrometry-based untargeted metabolomics approach was performed to dissect the metabolic differences in predose serum of the two groups...
March 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28270209/innovative-regenerative-medicines-in-the-eu-a-better-future-in-evidence
#10
EDITORIAL
Mark S Corbett, Andrew Webster, Robert Hawkins, Nerys Woolacott
BACKGROUND: Despite a steady stream of headlines suggesting they will transform the future of healthcare, high-tech regenerative medicines have, to date, been quite inaccessible to patients, with only eight having been granted an EU marketing licence in the last 7 years. Here, we outline some of the historical reasons for this paucity of licensed innovative regenerative medicines. We discuss the challenges to be overcome to expedite the development of this complex and rapidly changing area of medicine, together with possible reasons to be more optimistic for the future...
March 8, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28238125/post-marketing-regulation-of-medicines-withdrawn-from-the-market-because-of-drug-attributed-deaths-an-analysis-of-justification
#11
Igho J Onakpoya, Carl J Heneghan, Jeffrey K Aronson
INTRODUCTION: Several medicinal products have been withdrawn from the market because of drug-attributed deaths. However, there has been no investigation of whether such withdrawals were justified, and the extent to which confirmatory studies are used to investigate drug-adverse event relationships when deaths are reported is uncertain. We documented medicinal products withdrawn from the market because of drug-attributed deaths, identified confirmatory studies investigating the drug-adverse event relationships, examined whether withdrawals of medicinal products because of drug-attributed deaths after marketing were justified based on a mechanistic analysis, and examined the trends over time...
February 25, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28211195/a-comparison-of-the-new-japanese-expedited-approval-legislation-for-regenerative-medicine-product-with-the-existing-systems-of-the-united-states-and-european-union
#12
Yoji Jokura, Kazuo Yano, Masayuki Yamato
Expedited approval pathways/programs for drugs, biologics, or medical devices have been enacted for rapid product commercialization of innovative products in the United States (US) and European Union (EU). However, less innovative products are increasingly using these expedited pathways and frequently obligations to collect and report post-marketing data on approved products are being bypassed. The Japanese government recently enacted a new conditional and time-limited approval pathway dedicated to regenerative medicine products...
February 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28169302/precision-medicine-needs-randomized-clinical-trials
#13
REVIEW
Everardo D Saad, Xavier Paoletti, Tomasz Burzykowski, Marc Buyse
The advent of precision medicine has prompted profound changes in clinical cancer research, and the rising numbers of new therapeutic agents pose challenges in terms of the most appropriate trial designs and effects on the drug-approval process. In the past 5 years, some remarkably efficacious drugs have been approved based on evidence from uncontrolled phase I trials. We challenge the view that the expected benefits from new drugs are generally sufficient to forgo a randomized trial with patients assigned to a control arm (a regimen other than the experimental treatment)...
May 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28165177/intrauterine-death-rate-in-gastroschisis-following-the-introduction-of-an-antenatal-surveillance-program-retrospective-observational-study
#14
Helen Perry, Costa Healy, Diana Wellesley, Nigel J Hall, Melanie Drewett, David M Burge, David T Howe
AIM: To investigate whether an antenatal surveillance protocol including ultrasound and cardiotocograph monitoring reduces intrauterine death (IUD) in cases of gastroschisis. Secondary outcomes included neonatal death rate, mode of delivery and rate of intervention before planned time of delivery. METHODS: This was a retrospective observational study of all women with antenatally diagnosed gastroschisis who were managed according to the surveillance program between 2002 and 2015 in a tertiary fetal medicine and pediatric surgical center covering the Wessex region of England...
March 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28155078/the-promise-of-molecular-imaging-in-the-study-and-treatment-of-infectious-diseases
#15
Sanjay K Jain
Infectious diseases are a major threat to humanity, and it is imperative that we develop imaging tools that aid in their study, facilitate diagnosis, and guide treatment. The alarming rise of highly virulent and multi-drug-resistant pathogens, their rapid spread leading to frequent global pandemics, fears of bioterrorism, and continued life-threatening nosocomial infections in hospitals remain as major challenges to health care in the USA and worldwide. Early diagnosis and rapid monitoring are essential for appropriate management and control of infections...
February 2, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28061634/personalized-medicine-approach-for-an-exceptional-response-to-multiple-recurrent-and-metastatic-her2-positive-oropharyngeal-squamous-cell-carcinoma
#16
Nolan B Seim, Stephen Y Kang, Milan Bhandari, Riley G Jones, Theodoros N Teknos
INTRODUCTION: Advanced stage squamous cell carcinoma of the head and neck carries an overall poor prognosis, and survivorship gains have remained relatively stagnant compared to other malignancies due to its complex tumor biology and lack of proven effective targeting agents. METHODS: We present a case of an exceptional responder to molecular-targeted therapy for metastatic oropharyngeal squamous cell carcinoma using a chemotherapeutic agent FDA approved for breast cancer and targeting the HER2/Neu receptor in order to discuss the larger clinical implications...
April 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28057368/genomic-translational-research-paving-the-way-to-individualized-cardiac-functional-analyses-and-personalized-cardiology
#17
REVIEW
Ares Pasipoularides
For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28056571/compounds-compositions-and-methods-of-agelastatin-alkaloids-patent-evaluation-of-wo2015042239-a1
#18
Takehiko Yoshimitsu, Han W Tun
Agelastatins are a family of tetracyclic alkaloids isolated from marine sponges. The patent examined in this publication covers the chemical synthesis of agelastatins A to F and eight analogues and their therapeutic use against hematologic malignancies. The claim on the chemical synthesis features a novel biomimetic cyclization of a tricyclic precursor, which streamlines scalable access to agelastatins and their analogues. This new synthetic approach can potentially expedite the research on these compounds for therapeutic use against cancers by making them more easily available...
February 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28029082/probiotics-in-curing-allergic-and-inflammatory-conditions-research-progress-and-futuristic-vision
#19
Kuldeep Dhama, Shyma K Latheef, Ashok Kumar Munjal, Rekha Khandia, Hari Abdul Samad, Hafiz M N Iqbal, Sunil K Joshi
BACKGROUND: Probiotics constitute the viable and beneficial microbes, which offer a dietary means to sustain the balance of gastro-intestinal (GI) microflora. Owing to their multiple health benefits, these have recently gained wide attention among researchers for exploring their potential in safeguarding the health of humans and animals. Probiotics could also modulate host-immune responses, thereby help in counteracting the immunological dysfunctions. Probiotics can inhibit the systemic invasion of pathogens entering through the GI mucosa/ oral cavity and have been found to possess effective prophylactic and therapeutic utilities against various infectious pathogens as well as non-infectious diseases and disorders...
December 26, 2016: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/27986708/blastic-plasmacytoid-dendritic-cell-neoplasm-is-dependent-on-bcl2-and-sensitive-to-venetoclax
#20
Joan Montero, Jason Stephansky, Tianyu Cai, Gabriel K Griffin, Lucia Cabal-Hierro, Katsuhiro Togami, Leah J Hogdal, Ilene Galinsky, Elizabeth A Morgan, Jon C Aster, Matthew S Davids, Nicole R LeBoeuf, Richard M Stone, Marina Konopleva, Naveen Pemmaraju, Anthony Letai, Andrew A Lane
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and were uniformly sensitive to the BCL2 inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, and dynamic BH3 profiling. Animals bearing BPDCN patient-derived xenografts had disease responses and improved survival after venetoclax treatment in vivo Finally, we report on 2 patients with relapsed/refractory BPDCN who received venetoclax off-label and experienced significant disease responses...
February 2017: Cancer Discovery
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