Σάββατο 22 Ιουλίου 2017
The influence of systemic cryotherapy on selected hemodynamic parameters and the assessment of the safety of its use in patients with successfully treated hypertension
Source:Cryobiology
Author(s): Ewa Wujek-Krajewska, Agnieszka Cudnoch-Jędrzejewska, Liana Puchalska, Barbara Chybowska, Maciej Janiszewski, Dominika Klimczak, Marek Kuch
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Formicolio alla testa - Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog)
Formicolio alla testa
Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog) In questi ultimi due giorni, ogni tanto mi parte questa sensazione di "ragnetti", a volte mi parte dalle spalle e arriva fino quasi alla fronte, alle volte mi parte semplicemente dalla testa e arriva alla nuca. Poco dopo, mi prende qualche leggere ... |
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Alpha-gal
Alpha-gal: a carbohydrate (galactose-alpha-1,3-galactose) that has been identified as the cause of an unusual meat allergy that develops after a tick bite. The alpha-gal compound is found in the meat of all non-primate mammals. The allergic symptoms appear to be related to having experienced a bite from the Lone star tick (Amblyomma americanum). Unlike tick-borne infectious diseases like Lyme disease and Rocky Mountain Spotted Fever, the alpha-gal reaction is a true allergic reaction to the alpha-gal compound in meat that develops in people who have had bites from this type of tick. It is not due to an infectious organism spread by the tick bite. The exact reason for the relationship to tick bites and development of the allergy is unknown. The Lone Star tick is found in the US, mainly in the southeast and up to Iowa and into New England.
Symptoms include those of other allergic reactions and occur following the consumption of any type of meat. They can include:
- Hives or skin rash
- Nausea
- Vomiting or diarrhea
- Runny or congested nose
- Sneezing
- Worsening of asthma
- Headaches
Anaphylaxis, a severe and potentially deadly allergic reaction, is also possible. With alpha-gal allergy, the symptoms are not typical of many food allergies because they make take hours to develop in some people.
MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You
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Vaccini, in Lombardia a settembre tavolo per campagna informativa - ArezzoWeb.it
Vaccini, in Lombardia a settembre tavolo per campagna informativa
ArezzoWeb.it Per questo “il vaccino anti-Hpv assume un ruolo fondamentale nella prevenzione di questo e di tutta una serie di tumori (della vulva e della vagina, anale, del pene, testa-collo), anche nei maschi, che registrano nella maggior parte dei casi tassi di ... |
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Mom Beats Stage 4 Cancer After Doctors Give her Days to Live - WWL
WWL |
Mom Beats Stage 4 Cancer After Doctors Give her Days to Live
WWL As the pain continued to worsen, Ashley visited an ear, nose and throat specialist, who thought it was an infection in the salivary gland. She took some medication, and the lump shrunk. Ashley repeated this cycle of "medication and recovery" until she ... and more » |
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Crystallographic insights into a cobalt (III) sepulchrate based alternative cofactor system of P450 BM3 monooxygenase
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Saravanan Panneerselvam, Aamir Shehzad, Jochen Mueller-Dieckmann, Matthias Wilmanns, Marco Bocola, Mehdi D. Davari, Ulrich Schwaneberg
P450 BM3 is a multi-domain heme-containing soluble bacterial monooxygenase. P450 BM3 and variants are known to oxidize structurally diverse substrates. Crystal structures of individual domains of P450 BM3 are available. However, the spatial organization of the full-length protein is unknown. In this study, crystal structures of the P450 BM3 M7 heme domain variant with and without cobalt (III) sepulchrate are reported. Cobalt (III) sepulchrate acts as an electron shuttle in an alternative cofactor system employing zinc dust as the electron source. The crystal structure shows a binding site for the mediator cobalt (III) sepulchrate at the entrance of the substrate access channel. The mediator occupies an unusual position which is far from the active site and distinct from the binding of the natural redox partner (FAD/NADPH binding domain).
Graphical abstract
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Mom Beats Stage 4 Cancer After Doctors Give her Days to Live | wltx ... - WLTX.com
WLTX.com |
Mom Beats Stage 4 Cancer After Doctors Give her Days to Live | wltx ...
WLTX.com Editor's Note: Ashley made this video chronicling her mind-blowing journey from thinking she was going to die, to beating stage 4 cancer. Full story below. and more » |
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Size distribution, characterization and risk assessment of particle-bound polycyclic aromatic hydrocarbons during haze periods in Phayao Province, northern Thailand
Abstract
This study aims to investigate the concentrations and distributions of particulate matters and particle-bound polycyclic aromatic hydrocarbons (p-PAHs) in different inhalable fractions during haze periods in Phayao Province, northern Thailand and identify their possible emission sources through the characteristic ratios of selected PAHs, then determine an estimate of the potential lung cancer risk. The particulate samples were collected during haze periods between February 18 and April 8, 2014 and non-haze period from June 17 to 22, 2014 using an eight-stage cascade impactor. Each filter sample was weighed, ultrasonically extracted with acetonitrile, and then analyzed by SIM-GC-MS to identify 16 PAHs. The experimental results show that the concentrations of ultrafine (d ae < 0.4 μm), fine (0.4 μm < d ae < 2.1 μm), and coarse (d ae > 2.1 μm) particles during haze periods were in the range of 14.98–26.52 μg m−3, 62.57–101.52 μg m−3, and 55.27–89.68 μg m−3, respectively; whereas, their concentrations of 16 PAHs were in the range of 7.82–36.06 ng m−3, 26.66–61.89 ng m−3, and 9.35–30.93 ng m−3, respectively. The p-PAH distribution profiles during the haze periods were bimodal in coarse and accumulation modes, which are closely related to their particle size distributions. The characteristic ratios of BaP/BgP and INP/(BgP+InP) adsorbed on ultrafine and fine particles were 0.81–0.88 and 0.38–0.86 and 0.54–0.57 and 0.44–0.52, respectively. The values of B[a]Peq observed during haze periods varied from 9.57 to 29.05 ng m−3. Estimated lifetime cancer risks during haze periods ranged from 8.324 to 25.27 additional cases per 10,000 people exposed, which is about 10 times higher than that during non-haze period.
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The effects of adenotonsillar hypertrophy corrective surgery on left ventricular functions and pulmonary artery pressure in children
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Different inhibitory potential of sex hormones on NNK detoxification in vitro: a possible explanation for gender-specific lung cancer risk
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Metabolic Regulation of Glioma Stem-like Cells in the Tumor Micro-environment
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A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells
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Antioxidant and antibacterial activities of Pelargonium asperum and Ormenis mixta essential oils and their synergistic antibacterial effect
Abstract
In this work, the chemical composition, the antioxidant, and the antibacterial activities of two Moroccan essential oils less studied, extracted from Pelargonium asperum and Ormenis mixta, were investigated. According to the gas chromatography coupled to mass spectrometry analysis, citronellol (25.07%), citronellyl ester (10.52%), geraniol (10.46%), and buthyl anthranilate (5.93%) were found to be the major components of P. asperum, while O. mixta was mainly composed of D-germacrene (11.46%), 1,8-cineole (10.28%), and cis-methyl isoeugenol (9.04%). Moreover, O. mixta essential oil exhibited an important antioxidant activity being significantly higher than that exhibited by P. asperum oil (P < 0.001). As regards the antimicrobial activity of both essential oils, the zones of growth inhibition and the minimum inhibitory concentration values showed that P. asperum essential oil was more active than that of O. mixta. Thereafter, the impact of the binary combination of essential oils on their antimicrobial effect was investigated against Staphylococcus aureus using the fractional inhibitory concentration index calculation. The results showed a promising synergistic antibacterial interaction between essential oils studied.
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Metal megastars Iron Maiden bring 'Monstrance' performance to demon-themed Barclays concert - New York Daily News
New York Daily News |
Metal megastars Iron Maiden bring 'Monstrance' performance to demon-themed Barclays concert
New York Daily News ... screaming guitars and more energy than many younger bands of today. Frontman Bruce Dickinson quickly proved that he's made a full recovery from a tongue cancer diagnosis just a couple years ago, showing off his powerful vocals in the band's opener, ... and more » |
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Different inhibitory potential of sex hormones on NNK detoxification in vitro: a possible explanation for gender-specific lung cancer risk
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A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells
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Metabolic Regulation of Glioma Stem-like Cells in the Tumor Micro-environment
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Insurers set for backlash as they look to make stage one cancer not 'critical' enough for full cover - This is Money
This is Money |
Insurers set for backlash as they look to make stage one cancer not 'critical' enough for full cover
This is Money The industry argues that many stage one cancers are no longer 'critical' because five-year survival rates are close to 100 per cent. It also fears that as such cancers – thyroid for example – become more easily detectable, it will be hit by a tsunami ... |
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Judge suffering cancer jailed in Kocaeli, wife under detention in Tokat - Turkey Purge
Turkey Purge |
Judge suffering cancer jailed in Kocaeli, wife under detention in Tokat
Turkey Purge Mustafa Babayiğit, a Turkish judge who reportedly suffers from thyroid cancer, has been sent to jail by a Kocaeli court, while his wife, Songül Babayiğit who is also a judge, has been held in custody in Tokat. The judge couple is accused of having ... |
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Clinico-radiological Co-relation of Carcinoma Larynx and Hypopharynx: A Prospective Study
Abstract
The successful management of laryngeal and hypopharyngeal cancers requires accurate diagnosis, staging, assessment of patient wishes, and the selection of the most appropriate treatment for the individual patient. Imaging plays an important complementary role to clinical examination and endoscopy in the evaluation of laryngeal and hypopharyngeal cancers. The combined information allows the disease to be staged accurately. To correlate carcinoma larynx and hypopharynx clinically and radiologically and to know the accurate pre-therapeutic stage of the disease. A total of 50 cases were included in this study. After clinical TNM staging, CT scan was done to know the real extent of tumor, volume and nodal status. After that, TNM staging was revised based on radiological findings. The number of people who had been upstaged and downstaged after CT evaluation was measured. There were total of 50 cases of carcinoma larynx and hypopharynx in this study. There were 26 (52%) cases of carcinoma larynx and 24 (48%) cases of carcinoma hypopharynx. There were significant changes in T stage after radiological evaluation. Major changes were observed in T2 and T3 stages. Majority of cases (17) were having N1 disease after radiological evaluation. On comparing clinical and radiological staging of neck nodes, it was observed that upstaging occurred mainly in N0. Overall after radiological evaluation, 48% of our cases were upstaged, 48% remained in same stage and 4% were downstaged. By combining both clinical and radiological evaluation in laryngeal and hypopharyngeal cancers, a correct pre therapeutic staging can be obtained and thereby prompt treatment can be given.
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Mom beats stage 4 cancer after doctors give her days to live - WBIR-TV
WBIR-TV |
Mom beats stage 4 cancer after doctors give her days to live
WBIR-TV As the pain continued to worsen, Ashley visited an ear, nose and throat specialist, who thought it was an infection in the salivary gland. She took some medication, and the lump shrunk. Ashley repeated this cycle of "medication and recovery" until she ... and more » |
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Tories 'failed to tell cancer sufferers the truth' over impact of Brexit on radiotherapy resources - Mirror.co.uk
Mirror.co.uk |
Tories 'failed to tell cancer sufferers the truth' over impact of Brexit on radiotherapy resources
Mirror.co.uk They cited imports used in the treatment of thyroid cancer and bone tumours. Wim Oyen of the European Association of Nuclear Medicine added: “The transport of isotopes across borders is regulated. Rebel Tories have strongly refuted Damian Green's ... |
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Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer
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Speaking up against unsafe unprofessional behaviours: the difficulty in knowing when and how
Patient safety is a core focus now in medical education, with an increasing number of training programmes educating learners about its key tenets.1–3 Residents now undergo formal training about the importance of contributing to a culture of safety by speaking up to avoid errors or harm, but still face difficulties enacting these behaviours in practice.4 In this issue of the journal, Martinez et al have attempted to tease out differences in speaking-out behaviours between traditional and professionalism-related patient safety threats.5 The authors have raised several interesting points worthy of further exploration. In this editorial we focus on unprofessional behaviour as a potential threat to patient safety and propose some new ways of thinking about how to integrate research and lessons from both the patient safety and professionalism literature.
In the study by Martinez and colleagues, residents reported witnessing unprofessional behaviour more...
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Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix
The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome.
MethodsA detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed.
ResultsThe heterozygous LAMA5 mutation c.9418G>A (p.V3140M) was associated with skin anomalies, impaired scarring, night blindness, muscle weakness, osteoarthritis, joint and internal organs ligaments laxity, malabsorption syndrome and hypothyroidism. We demonstrated that the mutation alters the amount of LAMA5 peptides likely derived from protein cleavage and perturbs the activation of the epithelial-mesenchymal signalling, producing an unbalanced expression of Sonic hedgehog and GLI1, which are upregulated in cells from affected individuals, and of ECM proteins (COL1A1, MMP1 and MMP3), which are strongly inhibited. Studies carried out using human skin biopsies showed alteration of dermal papilla with a reduction of the germinative layer and an early arrest of hair follicle downgrowth. The knock-in mouse model, generated in our laboratory, shows similar changes in the tissues studied so far.
ConclusionsThis is the first report of a disease phenotype associated with LAMA5 mutation in humans.
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FOXP1-related intellectual disability syndrome: a recognisable entity
Mutations in forkhead box protein P1 (FOXP1) cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far.
MethodsWe correlate clinical and molecular data of 25 novel and 23 previously reported patients with FOXP1 defects. We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting.
ResultsPatients show ID, SLI, neuromotor delay (NMD) and recurrent facial features including a high broad forehead, bent downslanting palpebral fissures, ptosis and/or blepharophimosis and a bulbous nasal tip. Behavioural problems and autistic features are common. Brain, cardiac and urogenital malformations can be associated. More severe ID and NMD, sensorineural hearing loss and feeding difficulties are more common in patients with interstitial 3p deletions (14 patients) versus patients with monogenic FOXP1 defects (34 patients). Mutations result in impaired transcriptional repression and/or reduced protein stability.
ConclusionsFOXP1-related ID syndrome is a recognisable entity with a wide clinical spectrum and frequent systemic involvement. Our data will be helpful to evaluate genotype–phenotype correlations when interpreting next-generation sequencing data obtained in patients with ID and/or SLI and will guide clinical management.
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Regulating the advertising of genetic tests in Europe: a balancing act
Direct-to-consumer (DTC) genetic tests (GT) have provoked criticism over their potential adverse impact on public health. The European Parliament called for a ban on DTC advertising of GT during the debate for the adoption of a European Regulation on in vitro diagnostic medical devices. This proposal, however, was not ultimately retained in the final text. Instead, the regulation includes an article prohibiting misleading claims for this kind of advertising. These two different approaches raise questions about the optimal degree of regulation. Herein, we provide an overview of the ways GT have been advertised and related ethical issues. Subsequently, the laws regulating the advertising of GT at the European Union and national level are examined. Finally, recent regulatory developments are discussed.
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Clinico-radiological Co-relation of Carcinoma Larynx and Hypopharynx: A Prospective Study
Abstract
The successful management of laryngeal and hypopharyngeal cancers requires accurate diagnosis, staging, assessment of patient wishes, and the selection of the most appropriate treatment for the individual patient. Imaging plays an important complementary role to clinical examination and endoscopy in the evaluation of laryngeal and hypopharyngeal cancers. The combined information allows the disease to be staged accurately. To correlate carcinoma larynx and hypopharynx clinically and radiologically and to know the accurate pre-therapeutic stage of the disease. A total of 50 cases were included in this study. After clinical TNM staging, CT scan was done to know the real extent of tumor, volume and nodal status. After that, TNM staging was revised based on radiological findings. The number of people who had been upstaged and downstaged after CT evaluation was measured. There were total of 50 cases of carcinoma larynx and hypopharynx in this study. There were 26 (52%) cases of carcinoma larynx and 24 (48%) cases of carcinoma hypopharynx. There were significant changes in T stage after radiological evaluation. Major changes were observed in T2 and T3 stages. Majority of cases (17) were having N1 disease after radiological evaluation. On comparing clinical and radiological staging of neck nodes, it was observed that upstaging occurred mainly in N0. Overall after radiological evaluation, 48% of our cases were upstaged, 48% remained in same stage and 4% were downstaged. By combining both clinical and radiological evaluation in laryngeal and hypopharyngeal cancers, a correct pre therapeutic staging can be obtained and thereby prompt treatment can be given.
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Vaccini, in Lombardia a settembre tavolo per campagna informativa - Il Dubbio
Vaccini, in Lombardia a settembre tavolo per campagna informativa
Il Dubbio Per questo “il vaccino anti-Hpv assume un ruolo fondamentale nella prevenzione di questo e di tutta una serie di tumori (della vulva e della vagina, anale, del pene, testa-collo), anche nei maschi, che registrano nella maggior parte dei casi tassi di ... and more » |
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Mom beats stage 4 cancer after doctors give her days to live - WCSH-TV
WCSH-TV |
Mom beats stage 4 cancer after doctors give her days to live
WCSH-TV As the pain continued to worsen, Ashley visited an ear, nose and throat specialist, who thought it was an infection in the salivary gland. She took some medication, and the lump shrunk. Ashley repeated this cycle of "medication and recovery" until she ... and more » |
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DispatchCast: Let's talk about cancer - The Lake Country Echo
The Lake Country Echo |
DispatchCast: Let's talk about cancer
The Lake Country Echo Judi Laurence, (left) firefighter, emergency medical technician and mother of three, is this year's honorary cancer survivor for the Relay for Life of Crow Wing County. Laurence and Mary Crenna, Relay for Life event lead, were both diagnosed with ... and more » |
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Prescription Drug Price Paradox: Cost Analysis of Canadian Online Pharmacies versus US Medicare Beneficiaries for the Top 100 Drugs
Abstract
Background and objectives
Despite the introduction of Medicare Part D (MPD) and 2012 Affordable Care Act (ACA), patients have a cost burden due to increases in drug prices. To overcome cost barriers, some patients purchase their medications from Canadian online pharmacies as Canadian prescription drug prices are believed to be lower than US prescription drug prices. The objective of this study was to determine which top 100 Medicare drugs can be imported to the USA legally, and to determine which type of prescription drug would be more beneficial to be purchased from Canadian online pharmacies. Moreover, we also deemed it important to compare MPD beneficiary annual expenses with expenses patients would have when obtaining their prescriptions from Canadian online pharmacies.
Methods
We conducted a cost analysis from a patient perspective. A list of the top 100 Medicare drugs was compiled and information on drug prices was collected from three Canadian online pharmacies and four MPD plans in Virginia. The annual cost of each Medicare drug and percent change between Canadian online pharmacies and MPD were compared.
Results
A total of 78 drugs from the top 100 Medicare drugs were included in the final analysis. Seventy-six prescription drugs (97.4%) that could be purchased from Canadian online pharmacies showed a significantly lower average drug price percent change of −72.71% (P < 0.0001). The heart health/blood pressure subgroup had the highest number of drugs that could be purchased from Canadian online pharmacies.
Conclusion
The majority of prescription drugs can be purchased at lower prices from Canadian online pharmacies when compared to Medicare beneficiaries’ potential expenses. Purchasing medications from Canadian online pharmacies may be a viable option to address cost barriers.
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Infantile bullous pemphigoid with “string of pearls sign”. Raposo, Inês; Machado, Susana; Sampaio, Rita; Selores, Manuela
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Adalimumab-related alopecia in a patient affected by psoriasis. Melé-Ninot, Gemma; Expósito-Serrano, Vicente; Quintana Codina, Mònica; Iglesias Sancho, Maribel; Sánchez-Regaña, Manuel; Umbert Millet, Pablo; Salleras Redonnet, Montse
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Value of dermoscopy for the diagnosis of monilethrix. Baltazard, T; Dhaille, F; Chaby, G; Lok, C
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Acquired bullous acrodermatitis enteropathica as a histologic mimic of pemphigus foliaceus in a patient on parenteral nutrition. Wu, Davina; Fung, Maxwell A; Kiuru, Maija; Sharon, Victoria R
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Dermatology on Reddit: elucidating trends in dermatologic communications on the world wide web. Buntinx-Krieg, Talayesa; Caravaglio, Joseph; Domozych, Renee; Dellavalle, Robert P
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Dermatology on Snapchat. Patel, Ravi R; Yazd, N Kuseh Kalani; Dellavalle, Robert P
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Congenital isolated leukonychia. Davis-Fontenot, Kerri; Hagan, Caroline; Emerson, Ashley; Gerdes, Michelle
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Alopecia universalis unresponsive to treatment with tofacinitib: report of a case with a brief review of the literature. Salman, Andac; Sarac, Gonca; Ergun, Tulin
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Mycophenolate mofetil as a successful therapy for idiopathic granulomatous mastitis. Di Xia, Fan; Ly, Amy; Smith, Gideon P
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Herpes zoster ophthalmicus with associated vasculopathy causing stroke. Antia, Camila; Persad, Leah; Alikhan, Ali
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Ustekinumab to target granulomatous dermatitis in recalcitrant ulcerative necrobiosis lipoidica: case report and proposed mechanism. Hassoun, Lauren A; Sivamani, Raja K; Sharon, Victoria R; Silverstein, Marc A; Burrall, Barbara A; Tartar, Danielle M
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Generalized bullous fixed drug eruption imitating toxic epidermal necrolysis: a case report and literature review. Mitre, Victoria; Applebaum, Danielle S; Albahrani, Yasser; Hsu, Sylvia
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Disseminated cutaneous sporotrichosis presenting as a necrotic facial mass: Case and review. He, Yong; Ma, Chelsea; Fung, Maxwell; Fitzmaurice, Sarah
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Annular elastolytic giant cell granuloma: a “visible” diagnosis. Raposo, Inês; Mota, Fernando; Lobo, Inês; Brandão, José Ricardo; Selores, Manuela
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Cutaneous Balamuthia mandrillaris infection as a precursor to Balamuthia amoebic encephalitis (BAE) in a healthy 84-year-old Californian. Lehmer, Larisa M; Ulibarri, Gabriel E; Ragsdale, Bruce D; Kunkle, James
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Retronychia: an underdiagnosed disease. Robledo, A; Godoy, E; Manrique, E; Manchado, P
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Congenital juvenile xanthogranuloma with ulceration: a pediatric case report. Logue, Mary E; Elwood, Hillary; Smidt, Aimee
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Crystalline folliculitis revealed by non-aqueous staining technique. Siscos, Spyros Michael; Tran, Chi; Fischer, Ryan; Fraga, Garth
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A pediatric case of unusual melanocytic proliferation of the nail. Mathieu, Regine J; Vatanchi, Marjon; Heilman, Edward R; Glick, Sharon A
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The role of interleukin-17 in the pathogenesis of hidradenitis suppurativa. Yao, Yiqiu; Thomsen, Simon Francis
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Thyroid Education & Awareness Blooms with July Donations – Earn a Sunflower!
Please help us reach “31 Donations in 31 Days” during the month of July to support thyroid education and awareness in 2017.
- Your donation of just $25-$100 allows us to send patient information through the mail weekly to those who do not have a computer to access information online.
- Donations of $150-$200 helps us to manage printing and website costs for our thyroid patient information brochures.
- Support of $250 – $500 helps us to accomplish collaboration with thyroid experts in developing vital ATA thyroid treatment guidelines as well as, the processes necessary to carry out our research efforts.
Your support is valuable and keeps our work in motion!
The post Thyroid Education & Awareness Blooms with July Donations – Earn a Sunflower! appeared first on American Thyroid Association.
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Latest @AACR Clinical Research identifies new heritable mutations driving rare neuroendrocrine cancer… https://t.co/KfayVPRq9u
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A phase I/II trial and pharmacokinetic study of mithramycin in children and adults with refractory Ewing sarcoma and EWS–FLI1 fusion transcript
Abstract
Purpose
In a preclinical drug screen, mithramycin was identified as a potent inhibitor of the Ewing sarcoma EWS–FLI1 transcription factor. We conducted a phase I/II trial to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of mithramycin in children with refractory solid tumors, and the activity in children and adults with refractory Ewing sarcoma.
Patients and methods
Mithramycin was administered intravenously over 6 h once daily for 7 days for 28 day cycles. Adult patients (phase II) initially received mithramycin at the previously determined recommended dose of 25 µg/kg/dose. The planned starting dose for children (phase I) was 17.5 µg/kg/dose. Plasma samples were obtained for mithramycin PK analysis.
Results
The first two adult patients experienced reversible grade 4 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation exceeding the MTD. Subsequent adult patients received mithramycin at 17.5 µg/kg/dose, and children at 13 µg/kg/dose with dexamethasone pretreatment. None of the four subsequent adult and two pediatric patients experienced cycle 1 DLT. No clinical responses were observed. The average maximal mithramycin plasma concentration in four patients was 17.8 ± 4.6 ng/mL. This is substantially below the sustained mithramycin concentrations ≥50 nmol/L required to suppress EWS–FLI1 transcriptional activity in preclinical studies. Due to inability to safely achieve the desired mithramycin exposure, the trial was closed to enrollment.
Conclusions
Hepatotoxicity precluded the administration of a mithramycin at a dose required to inhibit EWS–FLI1. Evaluation of mithramycin in patients selected for decreased susceptibility to elevated transaminases may allow for improved drug exposure.
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Travel Experience Incubator Challenge seeking startups with innovative ideas
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A former biotech executive who's living with terminal cancer wants to reset expectations about new cancer treatments - Business Insider
Business Insider |
A former biotech executive who's living with terminal cancer wants to reset expectations about new cancer treatments
Business Insider In 2015, he was diagnosed with head and neck cancer, which was caused by human papillomavirus (or HPV), a sexually transmitted infection. After the diagnosis, Becker used his expertise in the drug industry to consider possible treatment options. One he ... and more » |
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Telehealth boosts Ahrens' treatment, eases travel concern - Daily Globe
Daily Globe |
Telehealth boosts Ahrens' treatment, eases travel concern
Daily Globe “Three years ago in September, I had a tumor removed from my tonsils,” explained Ahrens, a retiree in her late 60s who enjoys splitting her time between northern Iowa and the greater Dallas, Texas, area with her husband Rodney. Although Ahrens was ... |
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Quantifying Extensibility of Rotator Cuff Muscle with Tendon Rupture Using Shear Wave Elastography: A Cadaveric Study
Source:Journal of Biomechanics
Author(s): Taku Hatta, Hugo Giambini, Yoshiaki Itoigawa, Alexander W. Hooke, John W. Sperling, Scott P. Steinmann, Eiji Itoi, ai-Nan An
Surgical repair for large rotator cuff tear remains challenging due to tear size, altered muscle mechanical properties, and poor musculotendinous extensibility. Insufficient extensibility might lead to an incomplete reconstruction; moreover, excessive stresses after repair may result in repair failure without healing. Therefore, estimates of extensibility of cuff muscles can help in pre-surgical planning to prevent unexpected scenarios during surgery. The purpose of this study was to determine if quantified mechanical properties of the supraspinatus muscle using shear wave elastography (SWE) could be used to predict the extensibility of the musculotendionous unit on cadaveric specimens. Forty-five fresh-frozen cadaveric shoulders (25 intact and 20 with rotator cuff tear) were used for the study. Passive stiffness of 4 anatomical regions in the supraspinatus muscle was first measured using SWE. After detaching the distal edge of supraspinatus muscle from other cuff muscles, the detached muscle was axially pulled with the scapula fixed. The correlation between the SWE modulus and the extensibility of the muscle under 30 and 60 N loads was assessed. There was a significant negative correlation between SWE measurements and the experimental extensibility. SWE modulus for the anterior-deep region in the supraspinatus muscle showed the strongest correlation with extensibility under 30 N (r = 0.70, P < 0.001) and 60 N (r = 0.68, P < 0.001). Quantitative SWE assessment for the supraspinatus muscle was highly correlated with extensibility of musculotendinous unit on cadaveric shoulders. This technique may be used to predict the extensibility for rotator cuff tears for pre-surgical planning.
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07/21/17 PHD comic: 'Weekend Plans'
Piled Higher & Deeper by Jorge Cham |
www.phdcomics.com
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title: "Weekend Plans" - originally published 7/21/2017
For the latest news in PHD Comics, CLICK HERE! |
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How to choose the best journal for your case report
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IJERPH, Vol. 14, Pages 826: Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review
IJERPH, Vol. 14, Pages 826: Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review
International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14070826
Authors: Zijian Li Aaron Jennings
Abstract: The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human exposure pathways.
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Finding a life after losing your voice: Throat cancer survivors speak out - The Press
The Press |
Finding a life after losing your voice: Throat cancer survivors speak out
The Press When he did see an ear, nose, and throat specialist, however, cancer was found at the base of his tongue, caused by the human papillomavirus (HPV). "[People should] spend as much time thinking about cancer as they do thinking about winning the Lotto ... |
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A phase I/II trial and pharmacokinetic study of mithramycin in children and adults with refractory Ewing sarcoma and EWS–FLI1 fusion transcript
Abstract
Purpose
In a preclinical drug screen, mithramycin was identified as a potent inhibitor of the Ewing sarcoma EWS–FLI1 transcription factor. We conducted a phase I/II trial to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of mithramycin in children with refractory solid tumors, and the activity in children and adults with refractory Ewing sarcoma.
Patients and methods
Mithramycin was administered intravenously over 6 h once daily for 7 days for 28 day cycles. Adult patients (phase II) initially received mithramycin at the previously determined recommended dose of 25 µg/kg/dose. The planned starting dose for children (phase I) was 17.5 µg/kg/dose. Plasma samples were obtained for mithramycin PK analysis.
Results
The first two adult patients experienced reversible grade 4 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation exceeding the MTD. Subsequent adult patients received mithramycin at 17.5 µg/kg/dose, and children at 13 µg/kg/dose with dexamethasone pretreatment. None of the four subsequent adult and two pediatric patients experienced cycle 1 DLT. No clinical responses were observed. The average maximal mithramycin plasma concentration in four patients was 17.8 ± 4.6 ng/mL. This is substantially below the sustained mithramycin concentrations ≥50 nmol/L required to suppress EWS–FLI1 transcriptional activity in preclinical studies. Due to inability to safely achieve the desired mithramycin exposure, the trial was closed to enrollment.
Conclusions
Hepatotoxicity precluded the administration of a mithramycin at a dose required to inhibit EWS–FLI1. Evaluation of mithramycin in patients selected for decreased susceptibility to elevated transaminases may allow for improved drug exposure.
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Synthesis of a new insulin-mimetic anti-diabetic drug containing vitamin A and vanadium(IV) salt: Chemico-biological characterizations.
Synthesis of a new insulin-mimetic anti-diabetic drug containing vitamin A and vanadium(IV) salt: Chemico-biological characterizations.
Int J Immunopathol Pharmacol. 2017 Jul 01;:394632017719601
Authors: Adam AMA, Naglah AM, Al-Omar MA, Refat MS
Abstract
Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its -OH group. The vanadium(IV) compound is surrounded by two vitamin A molecules. The [VO(vitamin A)2(H2O)2] compound was synthesized in a binary solvent system consisting of MeOH/H2O (1:1 ratio) in alkaline media at pH = 8. This compound was characterized using Fourier transform infrared spectra (FT-IR), electronic spectra (UV-vis), effective magnetic moment, electron spin resonance (ESR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermal analysis (thermogravimetry (TG)-differential thermal analysis (DTA)). Anti-diabetic efficiency for the vanadium(IV) compound was assessed in streptozotocin (STZ)-induced diabetic mice. The results of the animal studies demonstrate the ability of the vanadium(IV) complex to act as an anti-diabetic agent, as measured by improvements of lipid profile, antioxidant activity (superoxide dismutase), malondialdehyde (MDA), glutathione, methionine synthase, and kidney and liver functions.
PMID: 28731364 [PubMed - as supplied by publisher]
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IJMS, Vol. 18, Pages 1591: The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer
IJMS, Vol. 18, Pages 1591: The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer
International Journal of Molecular Sciences doi: 10.3390/ijms18071591
Authors: Daniela D’Arcangelo Lavinia Tinaburri Elena Dellambra
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development. Keratinocytes are equipped with several epigenetic enzymes and transcription factors that shape the gene expression signatures of different epidermal layers and allow dynamic and coordinated expression changes to finely balance keratinocyte self-renewal and differentiation. These factors converge their activity in the basal layer to repress p16INK4a expression, protecting cells from senescence, and preserving epidermal homeostasis and regeneration. Several stress stimuli may activate p16INK4a expression that orchestrates cell cycle exit and senescence response. In the present review, we discuss the role of p16INK4a regulators in human epidermal SC self-renewal, aging and cancer.
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IJMS, Vol. 18, Pages 1593: Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters
IJMS, Vol. 18, Pages 1593: Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters
International Journal of Molecular Sciences doi: 10.3390/ijms18071593
Authors: Pierre Andreoletti Quentin Raas Catherine Gondcaille Mustapha Cherkaoui-Malki Doriane Trompier Stéphane Savary
The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins. The lack of a clear consensus on the secondary and tertiary structure of the TMDs weakens any structure-function hypothesis based on the very diverse ABCD1 mutations found in X-ALD patients. Therefore, we first reinvestigated thoroughly the structure-function data available and performed refined alignments of ABCD protein sequences. Based on the 2.85 Å resolution crystal structure of the mitochondrial ABC transporter ABCB10, here we propose a structural model of peroxisomal ABCD proteins that specifies the position of the transmembrane and coupling helices, and highlight functional motifs and putative important amino acid residues.
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Cancers, Vol. 9, Pages 94: Targeting Platelets for the Treatment of Cancer
Cancers, Vol. 9, Pages 94: Targeting Platelets for the Treatment of Cancer
Cancers doi: 10.3390/cancers9070094
Authors: Omar Elaskalani Michael Berndt Marco Falasca Pat Metharom
The majority of cancer-associated mortality results from the ability of tumour cells to metastasise leading to multifunctional organ failure and death. Disseminated tumour cells in the blood circulation are faced with major challenges such as rheological shear stresses and cell-mediated cytotoxicity mediated by natural killer cells. Nevertheless, circulating tumour cells with metastatic ability appear equipped to exploit host cells to aid their survival. Despite the long interest in targeting tumour-associated host cells such as platelets for cancer treatment, the clinical benefit of this strategy is still under question. In this review, we provide a summary of the latest mechanistic and clinical evidence to evaluate the validity of targeting platelets in cancer.
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Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells
Abstract
Reactive oxygen species (ROS) induced by bisphenol A (BPA) have been implicated in cellular oxidative damage and carcinogenesis. It is not known whether the potential alternatives of BPA, bisphenol AF (BPAF), and bisphenol F (BPF) can also induce ROS involved in mediating biological responses. This study evaluated the toxicity of BPAF and BPF on cell proliferation, DNA damage, intracellular calcium homeostasis, and ROS generation in MCF-7 human breast cancer cells. The results showed that BPAF at 0.001–1 μM and BPF at 0.01–1 μM significantly increased cell viability and at 25 and 50 μM, both compounds decreased cell viability. At 0.01–10 μM, both BPAF and BPF increased DNA damage and significantly elevated ROS and intracellular Ca2+ levels in MCF-7 cells. These biological effects were attenuated by the ROS scavenger N-acetylcysteine (NAC), indicating that ROS played a key role in the observed biological effects of BPAF and BPF on MCF-7 cells. These findings can deepen our understanding on the toxicity of BPAF and BPF, and provide basis data to further evaluate the potential health harm and establish environmental standard of BPAF and BPF.
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Heterogeneous reaction of NO 2 with soot at different relative humidity
Abstract
The influences of relative humidity (RH) on the heterogeneous reaction of NO2 with soot were investigated by a coated wall flow tube reactor at ambient pressure. The initial uptake coefficient (γ initial) of NO2 showed a significant decrease with increasing RH from 7 to 70%. The γ initial on “fuel-rich” and “fuel-lean” soot at RH = 7% was (2.59 ± 0.20) × 10−5 and (5.92 ± 0.34) × 10−6, respectively, and it decreased to (5.49 ± 0.83) × 10−6 and (7.16 ± 0.73) × 10−7 at RH = 70%, respectively. Nevertheless, the HONO yields were almost independent of RH, with average values of (72 ± 3)% for the fuel-rich soot and (60 ± 2)% for the fuel-lean soot. The Langmuir-Hinshelwood mechanism was used to demonstrate the negative role of RH in the heterogeneous uptake of NO2 on soot. The species containing nitrogen formed on soot can undergo hydrolysis to produce carboxylic species or alcohols at high RH, accompanied by the release of little gas-phase HONO and NO.
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Cerebrospinal Fluid Leakage During Temporal Bone Surgery: Selecting Intra-operative Dural Closure with a Dumbbell-Shaped Muscle Graft as a Surgical Approach
Abstract
Cerebrospinal fluid (CSF) leakages of the temporal bone may arise during mastoid surgery. The leakages can have multiple potential etiologies, for instance, using a cutting burr near the bony tegmen or monopolar electrocautery on the surface of the dura mater. In this paper, we introduced an effective and simple technique for the management of CSF leakages of the temporal bone. In a prospective case series, 36 patients (16 males and 20 females) who have had an experience of incidental or inevitable CSF otorrhea or otorhinorrhea during temporal bone surgery were selected. All patients were treated using a muscle graft in a dumbbell-shaped design through the dura defect at the Amir-Alam University Hospital between April 2005 and November 2008. The mean size of the defects was 5 mm (a range of 2–10 mm). A dumbbell-shaped autologous muscle graft was immediately successful in sealing the leakage in all patients. Only five patients (13.8%) had some evidence of leakage remaining on the day after the operation, which was subsequently resolved by conservative management in four of them (11.1%). Only one patient (2.7%) was subjected to a second operation for a new defect. Recurrence of CSF leakage or other related complications were not observed during about 7 years of follow up. A free autologous muscle graft, using the dumbbell technique through a small to moderate dura defect is an effective, easily performed, and safe method to seal iatrogenic leakages of the temporal bone.
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Clinical Thyroidology High-Impact Articles
FREE ACCESS through August 4, 2017.
Read Now:
Teprotumumab, an Antibody that Blocks the IGF-I Receptor, Causes Dramatic Improvement in Graves’ Orbitopathy
Jerome M. Hershman
For Papillary Thyroid Cancer Discovered During Pregnancy, Delayed Thyroid Surgery with Active Surveillance Is Appropriate
Jacques Orgiazzi
Can Imaging with FDG-PET Help Exclude Malignancy in Cytologically Indeterminate Thyroid Nodules?
Martin Biermann
The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.
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Clinical Thyroidology for the Public – Highlighted Article
From Clinical Thyroidology for the Public: Bariatric surgery for weight loss is becoming very common in the US. Obesity and hypothyroidism often occur in the same patient and ~18% of bariatric surgery patients require thyroid hormone therapy. Read More….
We welcome your feedback and suggestions. Let us know what you want to see in this publication.
Feedback & SuggestionsThe post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.
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Mom beats stage 4 cancer after doctors give her days to live - W*USA 9
W*USA 9 |
Mom beats stage 4 cancer after doctors give her days to live
W*USA 9 As the pain continued to worsen, Ashley visited an ear, nose and throat specialist, who thought it was an infection in the salivary gland. She took some medication, and the lump shrunk. Ashley repeated this cycle of "medication and recovery" until she ... |
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Brain Sciences, Vol. 7, Pages 92: Coagulopathy in the Setting of Mild Traumatic Brain Injury: Truths and Consequences
Brain Sciences, Vol. 7, Pages 92: Coagulopathy in the Setting of Mild Traumatic Brain Injury: Truths and Consequences
Brain Sciences doi: 10.3390/brainsci7070092
Authors: Joseph Herbert Andrew Guillotte Richard Hammer N. Litofsky
Mild traumatic brain injury (mTBI) is a common, although poorly-defined clinical entity. Despite its initially mild presentation, patients with mTBI can rapidly deteriorate, often due to significant expansion of intracranial hemorrhage. TBI-associated coagulopathy is the topic of significant clinical and basic science research. Unlike trauma-induced coagulopathy (TIC), TBI-associated coagulopathy does not generally follow widespread injury or global hypoperfusion, suggesting a distinct pathogenesis. Although the fundamental mechanisms of TBI-associated coagulopathy are far from clearly elucidated, several candidate molecules (tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), tissue factor (TF), and brain-derived microparticles (BDMP)) have been proposed which might explain how even minor brain injury can induce local and systemic coagulopathy. Here, we review the incidence, proposed mechanisms, and common clinical tests relevant to mTBI-associated coagulopathy and briefly summarize our own institutional experience in addition to identifying areas for further research.
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IJMS, Vol. 18, Pages 1594: Comparison of Two Stationary Phases for the Determination of Phytosterols and Tocopherols in Mango and Its By-Products by GC-QTOF-MS
IJMS, Vol. 18, Pages 1594: Comparison of Two Stationary Phases for the Determination of Phytosterols and Tocopherols in Mango and Its By-Products by GC-QTOF-MS
International Journal of Molecular Sciences doi: 10.3390/ijms18071594
Authors: Ana López-Cobo Beatriz Martín-García Antonio Segura-Carretero Alberto Fernández-Gutiérrez Ana Gómez-Caravaca
Two different gas chromatography coupled to quadrupole-time of flight mass spectrometry (GC-QTOF-MS) methodologies were carried out for the analysis of phytosterols and tocopherols in the flesh of three mango cultivars and their by-products (pulp, peel, and seed). To that end, a non-polar column ((5%-phenyl)-methylpolysiloxane (HP-5ms)) and a mid-polar column (crossbond trifluoropropylmethyl polysiloxane (RTX-200MS)) were used. The analysis time for RTX-200MS was much lower than the one obtained with HP-5ms. Furthermore, the optimized method for the RTX-200MS column had a higher sensibility and precision of peak area than the HP-5ms methodology. However, RTX-200MS produced an overlapping between β-sitosterol and Δ5-avenasterol. Four phytosterols and two tocopherols were identified in mango samples. As far as we are concerned, this is the first time that phytosterols have been studied in mango peel and that Δ5-avenasterol has been reported in mango pulp. α- and γ-tocopherol were determined in peel, and α-tocopherol was the major tocopherol in this fraction (up to 81.2%); however, only α-tocopherol was determined in the pulp and seed. The peel was the fraction with the highest total concentration of phytosterols followed by seed and pulp, and “Sensación” was the cultivar with the highest concentration of total phytosterols in most cases. There were no significant differences between quantification of tocopherols with both columns. However, in most cases, quantification of phytosterols was higher with RTX-200MS than with HP-5ms column.
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Connecting the Dots Between Fatty Acids, Mitochondrial Function, and DNA Methylation in Atherosclerosis
Abstract
Purpose of Review
The quest for factors and mechanisms responsible for aberrant DNA methylation in human disease—including atherosclerosis—is a promising area of research. This review focuses on the role of fatty acids (FAs) as modulators of DNA methylation—in particular the role of mitochondrial beta-oxidation in FA-induced changes in DNA methylation during the progression of atherosclerosis.
Recent Findings
Recent publications have advanced the knowledge in all areas touched by this review: the causal role of lipids in shaping the DNA methylome, the associations between chronic degenerative disease and mitochondrial function, the lipid composition of the atheroma, and the relevance of DNA hypermethylation in atherosclerosis.
Summary
Evidence is beginning to emerge, linking the dynamics of FA type abundance, mitochondrial function, and DNA methylation in the atheroma and systemically. In particular, this review highlights mitochondrial beta-oxidation as an important regulator of DNA methylation in metabolic disease. Despite the many questions still unanswered, this area of research promises to identify mechanisms and molecular factors that establish a pathological gene expression pattern in atherosclerosis.
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Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors
Source:Journal of Controlled Release, Volume 262
Author(s): Panagiotis Mastorakos, Clark Zhang, Eric Song, Young Eun Kim, Hee Won Park, Sneha Berry, Won Kyu Choi, Justin Hanes, Jung Soo Suk
The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain.
Graphical abstract
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Cerebrospinal Fluid Leakage During Temporal Bone Surgery: Selecting Intra-operative Dural Closure with a Dumbbell-Shaped Muscle Graft as a Surgical Approach
Abstract
Cerebrospinal fluid (CSF) leakages of the temporal bone may arise during mastoid surgery. The leakages can have multiple potential etiologies, for instance, using a cutting burr near the bony tegmen or monopolar electrocautery on the surface of the dura mater. In this paper, we introduced an effective and simple technique for the management of CSF leakages of the temporal bone. In a prospective case series, 36 patients (16 males and 20 females) who have had an experience of incidental or inevitable CSF otorrhea or otorhinorrhea during temporal bone surgery were selected. All patients were treated using a muscle graft in a dumbbell-shaped design through the dura defect at the Amir-Alam University Hospital between April 2005 and November 2008. The mean size of the defects was 5 mm (a range of 2–10 mm). A dumbbell-shaped autologous muscle graft was immediately successful in sealing the leakage in all patients. Only five patients (13.8%) had some evidence of leakage remaining on the day after the operation, which was subsequently resolved by conservative management in four of them (11.1%). Only one patient (2.7%) was subjected to a second operation for a new defect. Recurrence of CSF leakage or other related complications were not observed during about 7 years of follow up. A free autologous muscle graft, using the dumbbell technique through a small to moderate dura defect is an effective, easily performed, and safe method to seal iatrogenic leakages of the temporal bone.
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How music can shine a light on past worlds without words
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Surgical Management of Periocular Cancers: High- and Low-Risk Features Drive Treatment
Abstract
Purpose of Review
Recent advances in the treatment of eyelid tumors have centered on the excision, evaluation of margins, role of sentinel lymph node biopsy, and adjunctive/adjuvant systemic and radiation therapy. The purpose of this review is to elaborate on these advances.
Recent Findings
Mohs excision of basal cell carcinoma and squamous cell carcinoma continues to provide the greatest success in complete excision of the cancer, especially in those cases of high-risk disease including medial canthal location and recurrent disease. Sentinel lymph node biopsy has proven useful in the assessment of early regional metastasis in sebaceous cell carcinoma, melanoma, and Merkel cell carcinoma. The pathologic finding of perineural invasion is a high-risk feature in all periocular cancers, and adjuvant therapy should be considered. Targeted therapy shows great potential in situations that are not amenable to complete excision without sacrificing the globe.
Summary
Identification of high- and low-risk features in eyelid cancers allows a stratified approach to treatment. While high-risk features may require adjuvant therapy, larger margins, and sentinel lymph node biopsy, low-risk features may allow topical therapy to adequately address the condition. Monoclonal antibodies and small molecule inhibitors show great promise in the treatment of extensive disease.
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New Hypofractionation Radiation Strategies for Glioblastoma
Abstract
Purpose of Review
Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2 years despite the standard of care treatment of 6 weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM.
Recent Findings
Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity. HFRT over 1–3 weeks is already a standard of care for patients with advanced age or poor performance status. For young patients with good performance status, HFRT holds the promise of radiobiologically escalating the dose and potentially improving local control while maintaining quality of life.
Summary
Through the use of shorter radiotherapy fractionation regimens coupled with novel systemic agents, improved outcomes for patients with GBM may be achieved.
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Pathology of Neuroendocrine Tumours of the Female Genital Tract
Abstract
Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.
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quality of care; +903 new citations
903 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/07/22
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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How music can shine a light on past worlds without words
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Anatomical relation between nasal septum deviation and oropharynx volume in different facial patterns evaluated through cone beam computed tomography
Abstract
Introduction
The objective of this study was to establish the anatomical relation between nasal septum deviation (NSD) and oropharynx volume in different facial patterns using cone beam computed tomography (CBCT).
Methods
Ninety CBCT examinations were analyzed. InVivoDental software was used to evaluate cephalometric image reconstructions in terms of facial type, determined from cephalometric measurements indicative of growth direction; the presence of NSD was also evaluated. ITK-SNAP software was employed for delimitation of the oropharynx. Intra-examiner error methods were recorded. The results were subjected to parametric and non-parametric tests using Bioestat 5.0.
Results
A comparison of facial types revealed a significantly lower prevalence of NSD in the dolichofacial group compared with the brachyfacial and mesofacial groups (P = 0.0101 and 0.0149, respectively). In the total sample, there was a very strong positive relation between the presence of NSD and oropharynx space volume (P = 0.0162). The oropharynx volume was larger in all facial patterns in the presence of NSD.
Conclusion
The presence of NSD was not associated with facial type, although the oropharynx volume in patients with NSD increased. Therefore, deviation of the septum influences oropharynx volume.
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Neuroanatomical and resting state EEG power correlates of central hearing loss in older adults
Abstract
To gain more insight into central hearing loss, we investigated the relationship between cortical thickness and surface area, speech-relevant resting state EEG power, and above-threshold auditory measures in older adults and younger controls. Twenty-three older adults and 13 younger controls were tested with an adaptive auditory test battery to measure not only traditional pure-tone thresholds, but also above individual thresholds of temporal and spectral processing. The participants’ speech recognition in noise (SiN) was evaluated, and a T1-weighted MRI image obtained for each participant. We then determined the cortical thickness (CT) and mean cortical surface area (CSA) of auditory and higher speech-relevant regions of interest (ROIs) with FreeSurfer. Further, we obtained resting state EEG from all participants as well as data on the intrinsic theta and gamma power lateralization, the latter in accordance with predictions of the Asymmetric Sampling in Time hypothesis regarding speech processing (Poeppel, Speech Commun 41:245–255, 2003). Methodological steps involved the calculation of age-related differences in behavior, anatomy and EEG power lateralization, followed by multiple regressions with anatomical ROIs as predictors for auditory performance. We then determined anatomical regressors for theta and gamma lateralization, and further constructed all regressions to investigate age as a moderator variable. Behavioral results indicated that older adults performed worse in temporal and spectral auditory tasks, and in SiN, despite having normal peripheral hearing as signaled by the audiogram. These behavioral age-related distinctions were accompanied by lower CT in all ROIs, while CSA was not different between the two age groups. Age modulated the regressions specifically in right auditory areas, where a thicker cortex was associated with better auditory performance in older adults. Moreover, a thicker right supratemporal sulcus predicted more rightward theta lateralization, indicating the functional relevance of the right auditory areas in older adults. The question how age-related cortical thinning and intrinsic EEG architecture relates to central hearing loss has so far not been addressed. Here, we provide the first neuroanatomical and neurofunctional evidence that cortical thinning and lateralization of speech-relevant frequency band power relates to the extent of age-related central hearing loss in older adults. The results are discussed within the current frameworks of speech processing and aging.
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