PETALING JAYA: Deputy Health Minister Datuk Seri Dr Hilmi Yahaya has denied that he or anyone from his ministry gave their support to an individual who was found guilty of practising dentistry without a licence. In a statement issued by his personal secretary Aziaam Haji Ariffin on Sunday, Dr Hilmi said they never supported or compromised with individuals or groups that broke the law.
Neuroscientific and psychological research posits that there are two transdiagnostic facets of anxiety: anxious arousal and anxious apprehension. Though these two facets of anxiety are distinct, they are often subsumed into one domain (e.g., trait anxiety). The primary goal of the current study was to delineate the relationship between anxious arousal and cortical thickness versus the relationship between anxious apprehension and cortical thickness in a sample of typically functioning youth. The secondary aim was to determine where in the brain cortical thickness significantly correlated with both components of anxiety. Results indicated that the right anterior insula has a stronger relationship to anxious arousal, whereas the dorsolateral prefrontal cortex and left anterior insula were found to correlate with both anxious arousal and apprehension. We also observed volumetric differences in the amygdala and hippocampus between anxious arousal and anxious apprehension. Whereas anxious arousal, but not apprehension, predicted left amygdala volume, anxious apprehension, but not arousal, predicted right hippocampal volume. These findings demonstrated that there are both differences and similarities in the neural regions that contribute to independent facets of anxiety. Results are discussed in terms of previous findings from the affective and developmental cognitive neurosciences.
Neuroscientific and psychological research posits that there are two transdiagnostic facets of anxiety: anxious arousal and anxious apprehension. Though these two facets of anxiety are distinct, they are often subsumed into one domain (e.g., trait anxiety). The primary goal of the current study was to delineate the relationship between anxious arousal and cortical thickness versus the relationship between anxious apprehension and cortical thickness in a sample of typically functioning youth. The secondary aim was to determine where in the brain cortical thickness significantly correlated with both components of anxiety. Results indicated that the right anterior insula has a stronger relationship to anxious arousal, whereas the dorsolateral prefrontal cortex and left anterior insula were found to correlate with both anxious arousal and apprehension. We also observed volumetric differences in the amygdala and hippocampus between anxious arousal and anxious apprehension. Whereas anxious arousal, but not apprehension, predicted left amygdala volume, anxious apprehension, but not arousal, predicted right hippocampal volume. These findings demonstrated that there are both differences and similarities in the neural regions that contribute to independent facets of anxiety. Results are discussed in terms of previous findings from the affective and developmental cognitive neurosciences.
Most studies evaluating the use of essential oils (EO) as antibacterial agents focus mainly on minimal inhibitory concentrations (MIC) rather than minimal bactericidal concentrations (MBC). In this work, we compared MICs and MBCs of EO from condiment plants commonly used in Mediterranean Europe, namely Origanum vulgare, Salvia lavandulaefolia, Salvia officinalis, Salvia sclarea and Rosmarinus officinalis, aiming to evaluate their application as disinfecting agents in minimally processed produce. Outbreaks-related pathogens such as Listeria monocytogenes, Pseudomonas aeruginosa and Yarrowia lipolytica were used. Results showed that all EO were able to reduce bacterial growth in all bacterial strains tested, particularly O. vulgare. However, fewer EO exhibited bactericidal activities, and were only effective against one or two bacterial strains, hence eliminating the possibility to use them as broad range disinfectants. Furthermore, the necessary concentrations were too high for food application. Hence, our work suggests the need to evaluate MBC rather than MIC and questions EO usefulness in controlling undesired microorganisms. Overall, and despite the large volume of data published on EO, results obtained were not very encouraging for a realistic application on produce and question the viability of EOs as disinfecting agents in food.
This study evaluated the application of cashew gum, Arabic gum and starch on physical and thermal properties, and fatty acid profiles of spray-dried fish oil. A completely randomized design was used to evaluate the influence of the type of material on the properties of the microparticles. Hygroscopicity and solubility was higher for particles produced using cashew gum and reached 15 g/100 g and 85 g/100 g, respectively. Analyzing the thermogravimetric curves, it was found that cashew gum bulk showed two steps of degradation. For the microcapsules containing encapsulated fish oil in cashew gum, an extra degradation step at 471 °C was found. It was possible to verify the occurrence of diffused and wide peaks in the X-ray diffractograms for all three carbohydrate polymers. The particles produced presented spherical shape with cavities. The fatty acid profile for the fish oil changed only when using modified starch as wall material, where a significant loss of omega-3 fatty acids was observed. The particles produced with cashew gum had physical properties similar to those when applying materials commonly used and this biopolymer has the potential for application as a carrier in spray drying processes .
Cloud point assisted extraction of thymol from water extract of Ajwain (Trachyspermum Ammi L.) seeds has been reported. Effects of different operating conditions, i.e., concentration of surfactant, heating time and temperature in extraction efficiency were investigated. It was observed that maximum extraction efficiency of thymol was achieved with 30% (v/v) of SPAN 80 surfactant, 45 min of heating at 65 °C. Recovery of thymol from the surfactant complex was optimal at 1:3 coacervate phase to solvent (acetone) volume ratio. A semi-empirical correlation was proposed at the optimum time to predict the concentration of surfactant and temperature required for a desired yield.
Thunbergia laurifolia leaves were dried by freeze drying (FD) and microwave heat pump dehumidified air drying (MHPD). The dried leaves were stored in polypropylene (PP) or aluminum laminated pouches (ALP) at 15, 25 or 35 °C and 60% RH. The samples were held for 180 days to observe changes in moisture content, color, total phenolics, antioxidant activity, catechin and caffeic acid. In general, samples in PP had a greater increase in moisture. Total phenolics content and ferric-reducing antioxidant power values increased for 120 days, then decreased thereafter. After 180 days, both FD and MHPD samples packaged in ALP and stored at 15 °C had the greatest total phenolics, antioxidant activity and bioactive compounds amongst the storage conditions. The first-order equation best described degradation behavior of catechin and caffeic acid for both drying technologies investigated.
The impact of variable temperatures on mesocarp colour development and physico-chemical changes of mango fruits cv. Langra during ripening has been investigated. Physiological mature mango fruits were kept in temperature regulated chambers (20 and 25 °C) and at room temperature (29.8–33.6 °C). Progress in development of mesocarp colour, β-carotene, sensory quality (SQ) and total soluble solids (TSS) content of fruits were analysed periodically from 48 to 168 h of ripening period. The progress of ripening period was accompanied by an overall increase in colorimetric value redness (a*), yellowness (b*), chroma or saturation (C*), a reduction in lightness (L*) and hue angle (h 0) values. Colour development was found to be more in fruits ripened at higher temperatures than the fruits at lower temperature. β-carotene content of pulp improved with ripening of fruits up to 120 h of ripening period. Fruits ripened at 25 °C recorded maximum sensory quality score. Pearson's correlation matrix studies revealed that fruit mesocarp colour a*, b*, C* values were directly correlated with β-carotene, SQ and TSS with progress of ripening period.
Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC.
To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients.
In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase.
A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC.
MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.
Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation.
The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot.
Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA2-AA-COX-2-PGE2 pathway by inhibiting the expression of iPLA2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment.
Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.
Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC).
Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1-IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated.
The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up-regulate the p21WAF1/CIP1 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin-α (20 μmol/L). Moreover, IFI16-induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase-1 inhibitor Ac-YVAD-CMK (50 μmol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome.
IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.
Recent studies have reported the existence of stem cells in ovarian tissue that show enhanced proliferative and differentiation potential compared to other adult tissues. Based on this evidence, we hypothesized that ovarian tissue contained mesenchymal-like stem cells (MSC) that could be isolated using a novel rapid plastic adhesion technique.
We established MSC lines derived from ovarian and adipose tissue based on their ability to rapidly adhere to plastic culture dishes in the first 3 hours after plating and studied their potentiality in terms of molecular markers and differentiation capacity.
Morphological and kinetic properties of in vitro cultured ovarian MSC were similar to adipose-derived MSC, and both reached senescence after similar passage numbers. Ovarian-derived MSC expressed mesenchymal (CD90 and CD44) but not haematopoietic markers (CD34 and CD45), indicating similarity to adipose-derived MSC. Moreover, ovarian-derived MSC expressed NANOG, TERT, SOX2, OCT4 and showed extensive capacity to differentiate not only into adipogenic, osteogenic and chondrogenic tissue but also towards neurogenic and endodermal lineages and even precursors of primordial germ cells.
These results show for the first time the derivation of ovarian cells with the molecular properties of MSC as well as wide differentiation potential. Canine ovarian tissue is accessible, expandable, multipotent and has high plasticity, holding promise for applications in regenerative medicine.
This randomized controlled trial evaluated the impact of SurvivorCHESS, an eHealth intervention, on physical activity in colon cancer survivors and to explore the impact of SurvivorCHESS on quality of life and distress.
This was a two-arm single-blinded multi-site randomized controlled trial comparing a control group to an intervention group receiving a smartphone with the SurvivorCHESS program.
Participants using SurvivorCHESS (n = 144) increased their moderate to vigorous physical activities from 19.4 min at baseline to 50 min compared to the control group (n = 140) increasing from 15.5 to 40.3 min at 6 months (p = .083) but was not sustained 3 months after the study ended. No significant differences were found between groups over time for quality of life or distress items. Reports of physical symptoms were greater than other categories for distress items. Patients who had a higher body mass index and number of comorbid conditions were less likely to increase their physical activity. Self-determination theory including autonomous motivation and relatedness was not associated with the outcomes.
Physical activity did increase over time in both groups and was not significantly different with the use of the eHealth intervention, SurvivorCHESS, compared to the control group. The amount of SurvivorCHESS use was not associated with physical activity.
Increasing physical activity in colon cancer survivors has the potential to improve quality of life and reduce recurrences. Using smartphone-tracking devices may be useful in helping to change this health behavior.
Many patients with breast cancer work for pay at the time of their diagnosis, and the treatment plan may threaten their livelihood. Understanding work experiences in a contemporary population-based sample is necessary to inform initiatives to reduce the burden of cancer care.
Women who were 20 to 79 years old and had been diagnosed with stage 0 to II breast cancer, as reported to the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014-2015, were surveyed. Of the 3672 eligible women, 2502 responded (68%); 1006 who reported working before their diagnosis were analyzed. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for ≤1 month.
In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). One-third (33%) received chemotherapy. Most (84%) worked full-time before their diagnosis; however, only 50% had paid sick leave, 39% had disability benefits, and 38% had flexible work schedules. Surgical treatment was strongly correlated with missing >1 month of work (odds ratio [OR] for bilateral mastectomy with reconstruction vs lumpectomy, 7.8) and with stopping work altogether (OR for bilateral mastectomy with reconstruction vs lumpectomy, 3.1). Chemotherapy receipt (OR for missing >1 month, 1.3; OR for stopping work altogether, 3.9) and race (OR for missing >1 month for blacks vs whites, 2.0; OR for stopping work altogether for blacks vs whites, 1.7) also correlated. Those with paid sick leave were less likely to stop working (OR, 0.5), as were those with flexible schedules (OR, 0.3).
Working patients who received more aggressive treatments were more likely to experience substantial employment disruptions. Cancer 2017. © 2017 American Cancer Society.
Probiotics have been explored to stimulate gut health in weaned pigs, when they started to consume solid diet where mycotoxins could be present. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus RC007 on the intestinal toxicity of deoxynivalenol (DON) in an ex vivo model. Jejunal explants, obtained from 5-week-old crossbred castrated male piglets, were kept as control, exposed for 3 h to 10 μM DON, incubated for 4 h with 109 CFU/mL L. rhamnosus, or pre-incubated 1 h with 109L. rhamnosus and exposed to DON. Histological lesions were observed, para- and transcellular intestinal permeability was measured in Ussing chambers. The expression levels of mRNA encoding six inflammatory cytokines (CCL20, IL-10, IL-1β, TNFα, IL-8 and IL-22) were determined by RT-PCR. The expressions of the phosphorylated MAP kinases p42/p44 and p38 were assessed by immunoblotting. Exposure to DON induced histological changes, significantly increased the expression of CCL20, IL-1β, TNFα, IL-8, IL-22 and IL-10, increased the intestinal paracellular permeability and activated MAP kinases. Incubation with L. rhamnosus alone did not have any significant effect. By contrast, the pre-incubation with L. rhamnosus reduced all the effects of DON: the histological alterations, the pro-inflammatory response, the paracellular permeability and the phosphorylation of MAP kinases. Of note, L. rhamnosus did not adsorb DON and only slightly degrade the toxin. In conclusion, L. rhamnosus RC007 is a promising probiotic which, included as feed additive, can decrease the intestinal toxicity of DON.
To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy.
Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging.
All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11–30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE.
Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.
A new study reveals that patients with breast cancer who received more aggressive treatments were more likely to experience disruptions in employment. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings...
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2z94dZ6
via IFTTT
Potentially inappropriate medication (PIM) is an important issue for inpatient management; it has been associated with safety problems, such as increases in adverse drugs events, and with longer hospital stays and higher healthcare costs.
To compare two PIM-screening tools—STOPP/START and PIM-Check—applied to internal medicine patients. A second objective was to compare the use of PIMs in readmitted and non-readmitted patients.
A retrospective observational study, in the general internal medicine ward of a Swiss non-university hospital. We analysed a random sample of 50 patients, hospitalized in 2013, whose readmission within 30 days of discharge had been potentially preventable, and compared them to a sample of 50 sex- and age-matched patients who were not readmitted. PIMs were screened using the STOPP/START tool, developed for geriatric patients, and the PIM-Check tool, developed for internal medicine patients. The time needed to perform each patient's analysis was measured. A clinical pharmacist counted and evaluated each PIM detected, based on its clinical relevance to the individual patient's case. The rates of screened and validated PIMs involving readmitted and non-readmitted patients were compared.
Across the whole population, PIM-Check and STOPP/START detected 1348 and 537 PIMs, respectively, representing 13.5 and 5.4 PIMs/patient. Screening time was substantially shorter with PIM-Check than with STOPP/START (4 vs 10 minutes, respectively). The clinical pharmacist judged that 45% and 42% of the PIMs detected using PIM-Check and STOPP/START, respectively, were clinically relevant to individual patients' cases. No significant differences in the rates of detected and clinically relevant PIM were found between readmitted and non-readmitted patients.
Internal medicine patients are frequently prescribed PIMs. PIM-Check's PIM detection rate was three times higher than STOPP/START's, and its screening time was shorter thanks to its electronic interface. Nearly half of the PIMs detected were judged to be non-clinically relevant, however, potentially overalerting the prescriber. These tools can, nevertheless, be considered useful in daily practice. Furthermore, the relevance of any PIM detected by these tools should always be carefully evaluated within the clinical context surrounding the individual patient.
Potentially inappropriate medication (PIM) is an important issue for inpatient safety. The present study compare two PIM screening tools—STOPP/START and PIM-Check—applied to internal medicine patients. These patients are frequently prescribed PIMs. PIM-Check's PIM detection rate was three times higher than STOPP/START's, and its screening time was shorter thanks to its electronic interface. Even if nearly half of the PIMs detected were judged to be non-clinically relevant, these tools can nevertheless be considered useful in daily practice taking into account the clinical context of each patient.
Gibson Dental's new logo, brand mark and tagline highlight its core role as "Your Trusted Smile Partner." Additionally, its new responsively designed website, gibsondental.com, showcases Gibson's products, technology and rewards program.
This study explores two ideas to made an improvement on the artificial neural network (ANN)-based models for suspended sediment forecasting in several time steps ahead. In this regard, both observed and forecasted time series are incorporated as input variables of the models when applied for more than one lead time. Secondly, least-square ensemble models employing multiple wavelet-ANN models are developed to increase the performance of the single model. For this purpose, different wavelet families are linked with the ANN model and performance of each model is evaluated using error measures. The Skagit River near Mount Vernon in Washington county is selected as the case study. The daily flow discharge and suspended sediment concentration (SSC) in the current day are considered as input variables to predict suspended sediment concentration in the next day. For more lead times, the input structure is updated by adding the forecast of SSC in the previous time step. Results of this study demonstrate that incorporating both observed and predicted variables in the input structure improves performance of conventional models in which those only employ observed time series as input variables. Moreover, ensemble model developed for each lead time outperforms the best single wavelet-ANN model which indicates superiority of the ensemble model over the other one. Findings of this study reveal that acceptable forecasts of daily suspended sediment concentration up to 3 days in advance can be achieved using the proposed methodology.
This review discusses potential drug-drug interactions between statins and antimicrobials and provides clinician's guidance on how to manage these interactions.
In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials. Commonly used antimicrobials, such as macrolide antibiotics and azole antifungals, interact significantly with the CYP3A4 enzyme pathway similarly to lovastatin, simvastatin, and atorvastatin. Consequently, the potential for significant drug-drug interactions is increasing. In 2012, the US Food and Drug Administration strengthened warning labels for statins and dose adjustments related to drug-drug interactions. As such, it is imperative that clinicians are comfortable identifying drug-drug interactions between statins and antimicrobials and making appropriate therapy modifications as clinically warranted.
Statins and antimicrobials are frequently coprescribed, and the available pharmacokinetic data supports the potential for clinically significant drug-drug interactions. Macrolides and selected antifungals can significantly increase drug levels of select statins, particularly those metabolized by the CYP3A4 pathway. Contrarily, rifampin can significantly reduce drug levels of statins, limiting their efficacy. Future research efforts should identify interventions to improve clinician recognition of these drug-drug interactions and the prevention of unwarranted statin-related adverse effects.
Auricular hematoma: a collection of blood (hematoma) in the tissues of the outer ear. It occurs as a result of blunt, shearing trauma applied to the ear and is an injury most often seen in wrestlers. Symptoms and signs include red or bluish discoloration, swelling, and deformity of the outer ear. Also known as ear hematoma. See also hematoma.
Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.
Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls.
Publication date: 1 December 2017
Source:Cancer Letters, Volume 410
Author(s): Bryan Hoang, Mark J. Ernsting, Wei-Hsin Sophia Tang, Joseph Bteich, Elijus Undzys, Taira Kiyota, Shyh-Dar Li
Effective treatment of metastatic castration resistant prostate cancer (mCRPC) remains an unmet challenge. Cabazitaxel (CBZ) is approved for mCRPC after docetaxel (DTX) failure, but the improvement in survival is only moderate (∼2 months) and patients suffer from significant side effects. Here, we report the development of a polymer based delivery system for CBZ to improve its safety and efficacy against DTX-resistant mCRPC. CBZ was conjugated to a carboxymethylcellulose-based polymer (Cellax-CBZ), which self-assembled into ∼100 nm particles in saline and exhibited sustained drug release in serum at 10%/day. Cellax-CBZ delivered 157-fold higher CBZ to PC3-RES prostate tumor in mice and could be safely administered at a 25-fold higher dose compared to free CBZ, resulting in superior tumor inhibition in multiple mice models of DTX-resistant CRPC. In a metastatic bone model of CRPC, Cellax-CBZ significantly improves overall survival with a 70% long-term survival rate to day 120, while mice treated with free CBZ had a median survival of 40 days. Cellax-CBZ induced mild and reversible neutropenia in mice but no other tissue damage. Cellax-CBZ showed significant potential for improving therapy of mCRPC over clinically approved CBZ.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2kwps3L
via IFTTT
This study aimed to isolate and characterize filamentous fungi onychomycosis agents in a military population assisted at a hospital outpatient clinic.
In onychomycosis, the fungi colonize the subungual region causing thickening, discoloration, or cracking of the nail bed. Samples were collected from patients with clinical sights of onychomycosis.
Among 80 samples collected, 50 (62.5%) had positive culture. Isolated dermatophytes (86%) were Trichophyton rubrum (21; 42%), T. mentagrophytes var. interdigitale (19; 38%), and Microsporum gypseum (3; 6%) and non-dermatophyte molds were Fusarium spp. (1; 2%), Scytalidium spp. (1; 2%), and Chaetomium globosum (5; 10%). Minimal inhibitory concentrations (mg/L) of terbinafine, itraconazole, and fluconazole necessary to inhibit 50/90% of the isolates were respectively 0.015/0.06, 0.06/0.12, and 32/32. Etiological agents of onychomycosis in a military hospital are similar as reported in studies for the general population. High prevalence of non-dermatophytic agents was observed, especially for Chaetomium globosum.
Pancreatic adenocarcinoma remains a major therapeutic challenge, as the poor (<8%) 5-year survival rate has not improved over the last three decades. Our previous preclinical data showed cooperative attenuation of pancreatic tumor growth when dasatinib (Src inhibitor) was added to erlotinib (EGFR inhibitor) and gemcitabine. Thus, this study was designed to determine the maximum-tolerated dose of the triplet combination. Standard 3 + 3 dose escalation was used, starting with daily oral doses of 70 mg dasatinib and 100 mg erlotinib with gemcitabine on days 1, 8, and 15 (800 mg/m2) of a 28-day cycle (L0). Nineteen patients were enrolled, yet 18 evaluable for dose-limiting toxicities (DLTs). One DLT observed at L0, however dasatinib was reduced to 50 mg (L−1) given side effects observed in the first two patients. At L−1, a DLT occurred in 1/6 patients and dose was re-escalated to L0, where zero DLTs reported in next four patients. Dasatinib was escalated to 100 mg (L1) where 1/6 patients experienced a DLT. Although L1 was tolerable, dose escalation was stopped as investigators felt L1 was within the optimal therapeutic window. Most frequent toxicities were anemia (89%), elevated aspartate aminotransferase (79%), fatigue (79%), nausea (79%), elevated alanine aminotransferase (74%), lymphopenia (74%), leukopenia (74%), neutropenia (63%), and thrombocytopenia (63%), most Grade 1/2. Stable disease as best response was observed in 69% (9/13). Median progression-free and overall survival was 3.6 and 8 months, respectively. Dasatinib, erlotinib, and gemcitabine was safe with manageable side effects, and with encouraging preliminary clinical activity in advanced pancreatic cancer.
Electric power system involves different fields and disciplines which addressed the economic system, energy system, and environment system. Inner uncertainty of this compound system would be an inevitable problem. Therefore, an inexact multistage fuzzy-stochastic programming (IMFSP) was developed for regional electric power system management constrained by environmental quality. A model which concluded interval-parameter programming, multistage stochastic programming, and fuzzy probability distribution was built to reflect the uncertain information and dynamic variation in the case study, and the scenarios under different credibility degrees were considered. For all scenarios under consideration, corrective actions were allowed to be taken dynamically in accordance with the pre-regulated policies and the uncertainties in reality. The results suggest that the methodology is applicable to handle the uncertainty of regional electric power management systems and help the decision makers to establish an effective development plan.
Psoriasis is a known risk factor for neuro-psychiatric diseases among adults. Less is known regarding adolescents.
Investigating the association between psoriasis and neuro-psychiatric comorbidity and social skills among adolescents.
A population based cross-sectional study between January 1st, 1999 and January 1st, 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate to severe psoriasis, respectively. All psoriasis patients were diagnosed by a dermatologist. Neuro-psychiatric diseases were diagnosed by a neurologist and a psychiatrist, accordingly. Social skills were evaluated by a psychosocial assessment. Psoriasis patients were compared to 884653 healthy control patients by a multivariate analysis adjusted for age, sex, country of origin, socio-economic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity which could only be evaluated for part of the recruitment years, by a univariate analysis.
Overall chronic headaches (8.1% vs. 3.4%), intermediate frequency migraine (4.8% vs. 1.6%), low frequency migraine and non-migraine headaches (3.4% vs. 1.8%) were associated only with moderate to severe psoriasis compared to healthy controls [Adjusted odds ratios (adj. ORs) 1.9, 2.3, 1.5; 95% confidence intervals (CIs) 1.6-2.4, 1.8-3.0 and 1.1-2.1, respectively]. Anxiety disorders (2.1% vs. 0.7%) and impaired social adjustment skills (7.5% vs. 4.2%) were also associated only with moderate to severe psoriasis compared to healthy controls (ORs 2.9, 1.9; 95% CIs 1.6-5.5 and 1.3-2.6; Of 466 vs. 265023, respectively).
Psoriasis among adolescents is associated with neuro-psychiatric co-morbidities and impaired adjustment skills, depending on disease severity.
This article is protected by copyright. All rights reserved.
Several years ago, Labette Community College took a look at its and other health career programs in Southeast Kansas and the state to determine what new choices it could offer so more students could achieve career goals.
The latest installment of On My Shelf takes us into sex tourism in the Dominican Republic.
-- Read more on ScientificAmerican.com
The latest installment of On My Shelf takes us into sex tourism in the Dominican Republic.
-- Read more on ScientificAmerican.com
The presence of virulence factors (VFs) and mechanisms of quinolones and macrolide resistance was analyzed in Campylobacter spp. from a pediatric cohort study in Lima. In 149 isolates (39 Campylobacter jejuni and 24 Campylobacter coli from diarrheic cases; 57 C. jejuni and 29 C. coli from controls), the presence of the cdtABC and cadF genes and iam marker was established. Nalidixic acid, ciprofloxacin, erythromycin, and azithromycin susceptibilities were established in 115 isolates and tetracycline-susceptibility was established in 100 isolates. The presence of mutations in the gyrA, parC, and 23S rRNA genes was determined. The cadF gene and all genes from the cdtABC operon were significantly more frequent among C. jejuni (); the iam marker was more frequent in C. coli (). No differences were observed in VFs between cases and controls. Almost all isolates were tetracycline-resistant; nalidixic acid and ciprofloxacin resistance reached levels of 90.4% and 88.7%, respectively. Resistance to macrolides was 13% (C. jejuni 4.3%; C. coli 26.1%). Resistance to ciprofloxacin was related to GyrA Thr86 substitutions, while 13 of 15 macrolide-resistant isolates possessed a 23S rRNA mutation (A2075G). Differences in the presence of VFs and alarming levels of resistance to tested antimicrobial agents were observed among C. jejuni and C. coli.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wFU9F7
via IFTTT
This paper presents an analysis of data collected through the Waterloo WeBike project: a field trial in which over 30 sensor-equipped electric bicycles (e-bikes) were given to members of the University of Waterloo for personal use. Our dataset includes e-bike trips and battery charging sessions spanning nearly three years, from summer 2014 until spring 2017. We also conducted three surveys both before and during the trial. Our main findings were that the primary purpose of the e-bikes in our trial was for commuting, with most trips lasting less than 20 minutes and most trips taking place in the summer months. Our battery charging analysis revealed no evidence of range anxiety, and our analysis of survey results showed little correlation between anticipated and actual use. Furthermore, when asked about their opinions about various modes of transportation, our participants rated regular bicycles higher than e-bikes even after becoming familiar with e-bikes through the field trial. Based on our analysis, we draw several conclusions, including the fact that the general population in Canada is still unaware of e-bikes and their potential. Moreover, e-bike manufacturers should target sales to nonbike users, such as seniors, rather than trying to displace sales of regular bicycles.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g3Ub6Z
via IFTTT
Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale. The review will progress from the utilities of basic spin-relaxation contrasts in cancer imaging to more advanced imaging methods that measure tumor-distinctive parameters such as perfusion, water diffusion, magnetic susceptibility, oxygenation, acidosis, redox state, and cell death. Analytical methods to assess tumor heterogeneity are also reviewed in brief. Although the clinical utility of tumor heterogeneity from imaging is debatable, the quantification of tumor heterogeneity using functional and metabolic MR images with development of robust analytical methods and improved MR methods may offer more critical roles of tumor heterogeneity data in clinics. MRI/MRS can also provide insightful information on pharmacometabolomics, biomarker discovery, disease diagnosis and prognosis, and treatment response. With these future directions in mind, we anticipate the widespread utilization of these MR-based techniques in studying in vivo cancer biology to better address significant clinical needs.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wHwown
via IFTTT
The purpose of this study was to understand the pros and cons of the lengthening nails which have their own mechanical mechanism; we propose a classification for "device-related complications" arising from mechanical properties of the nail itself. From March 2010 to March 2014, 115 segments of lower limb lengthening were performed using intramedullary lengthening nails (35 ISKD, 34 PRECICE1, and 46 PRECICE2). Device-related complications were sorted into three categories according to a new classification: distraction control-related (type I), stability related (type II), and other device-related (type III); these were subdivided using Paley's concept of problems (a), obstacles (b), and sequel (c). Most common complications were distraction mechanism issues (type I) in ISKD and mechanical strength related ones (type II) in PRECICE1 and PRECICE2. Sixty percent (21/35) of ISKD had device-related problems. In PRECICE1 group, 8.8% (3/34) had device-related problems, and 8.8% (3/34) showed device-related obstacle. In PRECICE2, forty-four percent (20/46) had device-related problems. In conclusion, a new classification showed more clearly the differences of mechanical characteristics of different nails. The most essential thing of future lengthening nail development is minimizing the types I and II complications. Further study is necessary to compare the mechanical strength and stability of lengthening nails.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g31AU7
via IFTTT
Publication date: Available online 8 October 2017
Source:Cellular Signalling
Author(s): Ewelina Jurewicz, Elżbieta Wyroba, Anna Filipek
S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al., 2014). In this work we describe for the first time the mechanism of S100A6 secretion and signaling pathways activated by the S100A6-integrin β1 complex. We show that colchicine suppressed the release of S100A6 into the cell medium, which indicates that the protein might be secreted via a tubulin–dependent pathway. By applying double immunogold labeling and immunofluorescence staining we have shown that S100A6 associates with microtubules in WJMS cells. Furthermore, results obtained from immunoprecipitation and proximity ligation assay (PLA), and from in vitro assays, reveal that S100A6 is able to form complexes with α and β tubulin in these cells, and that the S100A6-tubulin interaction is direct. We have also found that the S100A6 protein, due to binding to integrin β1, activates integrin-linked kinase (ILK), focal adhesion kinase (FAK) and p21-activated kinase (PAK). Our results suggest that binding of S100A6 to integrin β1 affects cell adhesion/proliferation due to activation of ILK and FAK signaling pathways.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2y66K6i
via IFTTT
Publication date: Available online 8 October 2017
Source:Journal of Infection and Chemotherapy
Author(s): Hiroaki Nishioka, Hiroshi Takegawa, Hiroki Kamei
Infections occur more frequently in patients receiving biologics. However, cryptococcal infection is uncommon in patients receiving tocilizumab, an interleukin-6 inhibitor, in contrast to patients receiving tumor necrosis factor-α inhibitors. In this report, we describe a case of disseminated cryptococcosis in a 55-year-old man who was receiving tocilizumab every 2 weeks along with daily prednisolone and cyclosporine for Castleman's disease. He initially developed cellulitis on both upper limbs, and his condition worsened despite antibacterial therapy. Chest X-ray scanning and computed tomography demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was detected in blood, skin, and sputum cultures. He was diagnosed with disseminated cryptococcosis, and successfully treated with liposomal amphotericin B for a week followed by oral fluconazole for 11 months. The findings of this study indicate that cryptococcosis should be considered during the differential diagnosis of infection in patients receiving tocilizumab, especially in the presence of other risk factors for infections or a short tocilizumab dosing interval.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2y1LxN9
via IFTTT
While her actual anniversary was in September, the celebrations began in August and have continued into October. Her staff held a luncheon for her, and she has received cake, wine, balloons, flowers and other gifts over time.
Six C-band weather radars located in Europe (Finland, Netherlands, and Switzerland) have been used to monitor the slowly varying solar emission, which is an oscillation with an amplitude of several decibels and a period of approximately 27 days. It is caused by the fact that the number of active regions that enhance the solar radio emission with respect to the quiet component, as seen from Earth, varies because of the Sun's rotation about its axis. The analysis is based on solar signals contained in the polar volume data produced during the operational weather scan strategy. This paper presents hundreds of daily comparisons between radar estimates and the Sun's reference signal, during the current active Sun period (year 2014). The Sun's reference values are accurately measured by the Dominion Radio Astrophysical Observatory (DRAO) at S-band and converted to C-band using a standard DRAO formula. Vertical and horizontal polarization receivers are able to capture the monthly oscillation of the solar microwave signal: the standard deviation of the log-transformed ratio between radars and the DRAO reference ranges from 0.26 to 0.4 dB. A larger coefficient (and a different value for the quiet Sun component) in the standard formula improves the agreement.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hXHJGi
via IFTTT
Publication date: Available online 7 October 2017
Source:Biochimie
Author(s): Indu Kumari, Mushtaq Ahmed, Yusuf Akhter
Trichodiene synthase, a terpene fold enzyme catalyzes the first reaction of trichodermin biosynthesis that is an economically important secondary metabolite. Sequence search analysis revealed that the proteins containing terpene fold are present in bacteria, fungi and plants. Terpene fold protein from Selaginella moellendorffii, a lycophyte, appeared at the interface of the microbes and plants in the evolutionary scale. Amino acid residues present around the catalytic pocket determines the size of the substrate as well as product molecules. It has been observed that the overall molecular evolution of the catalytic pockets dictates the choice of substrates/products of the proteins. It was further observed that N-terminus of multi-domain terpene fold proteins may assist in the interactions with the pyrophosphate part of the substrates. The phylogenetic analysis of these proteins revealed that the enzymes are clustered into groups based on the domains present additional to the catalytic domains. We have also observed inter-domain 'puckering forceps' type motions in the multi-domains using normal mode analyses which were further correlated with their functions. The evolutionary clustering of these proteins was also influenced by the presence/absence of cofactor interacting motifs. These results may be used to modify/enhance the functions of these enzymes using protein engineering methods.
Publication date: Available online 7 October 2017
Source:Biochimie
Author(s): Luc Pénicaud
Vascularization and innervation of the islet of Langerhans are highly interconnected and are critical for intercellular and intertissular communication. They are both involved in the control of islet blood flow which has been shown to have an important role in the control of endocine secretion. Both parameters are disturbed during the course of metabolic pathologies and particularly diabetes. A better understanding of these mechanisms has and will greatly benefit from the rapidly-emerging technologies particularly in vivo imaging enabling to study both anatomy and functions of the islet.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2yy53RV
via IFTTT
Publication date: Available online 7 October 2017
Source:Biochimie
Author(s): Wei Zhang, Weitang Yuan, Junmin Song, Shijun Wang, Xiaoming Gu
ObjectiveHypoxia is a common phenomenon in solid tumor microenvironment. Thereby, the aim of this study was to investigate the molecular mechanisms of tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC.MethodsExpression of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1α) and autophagy related protein (LC3) were initially assessed in human CRC tissues and in a series of CRC cell lines. The relationship of CPS1-IT1, HIF-1α and autophagy were analyzed in CRC were performed through in vitro and in vivo functional assays.ResultsExpression of CPS1-IT1 were significantly reduced, while HIF-1α and LC3-II were increased in CRC tissues and cell lines. Then, in vitro assays revealed that CPS1-IT1 suppresses EMT and autophagy by inhibiting the activation of HIF-1α in CRC. An in vivo animal model also demonstrated the tumor suppressor mechanism of CPS1- IT1.ConclusionIn this study, we found that hypoxia induce autophagy, and inhibition of autophagy could suppress tumor metastasis and EMT in CRC. Additionally, lncRNA CPS1-IT might suppresses metastasis and EMT by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α in CRC.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g2MvBN
via IFTTT
Publication date: Available online 7 October 2017
Source:Journal of Epidemiology and Global Health
Author(s): Sarah E. Ahlbrand, Madhukar Pai
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2y2OJIl
via IFTTT
Publication date: Available online 7 October 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Min-Kyu Kwak, MyungHee Ku, Sa-Ouk Kang
BackgroundHigh methylglyoxal content disrupts cell physiology, but mammals have scavengers to prevent glycolytic and mitochondrial dysfunctions. In yeast, methylglyoxal accumulation triggers methylglyoxal-oxidizing alcohol dehydrogenase (Adh1) activity. While methylglyoxal reductases and glyoxalases have been well studied in prokaryotes and eukaryotes, experimental evidence for methylglyoxal dehydrogenase (Mgd) and other catalytic activities of this enzyme affecting glycolysis and the tricarboxylic acid cycle is lacking.MethodsA glycine-rich cytoplasmic Mgd protein, designated as Mgd1/Grp2, was isolated from glutathione-depleted Candida albicans. The effects of Mgd1/Grp2 activities on metabolic pathophysiology were investigated using knockout and overexpression mutants. We measured glutathione-(in)dependent metabolite contents and metabolic effects, including viability, oxygen consumption, ADH1 transcripts, and glutathione reductase and α-ketoglutarate dehydrogenase activities in the mutants. Based on the findings, methylglyoxal-oxidizing proteins were monitored to determine effects of MGD1/GRP2 disruption on methylglyoxal-scavenging traits during glutathione deprivation.ResultsMethylglyoxal-oxidizing NAD(H)-linked Mgd1/Grp2 was found solely in glutathione auxotrophs, and it catalyzed the reduction of both methylglyoxal and pyruvate. MGD1/GRP2 disruptants showed growth defects, cell-cycle arrest, and methylglyoxal and pyruvate accumulation with mitochondrial impairment, regardless of ADH1 compensation. Other methylglyoxal-oxidizing enzymes were identified as key glycolytic enzymes with enhanced activity and transcription in MGD1/GRP2 disruptants, irrespective of glutathione content.ConclusionsFailure of methylglyoxal and pyruvate dissimilation by Mgd1/Grp2 deficiency leads to poor glutathione-dependent redox regulation despite compensation by Adh1.General significanceThis is the first report that multifunctional Mgd activities contribute to scavenging methylglyoxal and pyruvate to maintain metabolic homeostasis and the redox pool via glycolytic enzymes and Adh1 expression.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hWAy16
via IFTTT
Publication date: Available online 7 October 2017
Source:Experimental Cell Research
Author(s): Sadie L. Hebert, Krysta R. Fitzpatrick, Samantha A. McConnell, Anja Cucak, Ching Yuan, Linda K. McLoon
One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7. EOM-derived and LEG-derived EECD34 cells were treated with vehicle, retinoic acid, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG-derived cells expressed desmin and fused when treated with retinoic acid compared to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We hypothesize that retinoic acid signaling aids in the maintenance of large numbers of undifferentiated myogenic precursor cells in the EOM, which would be required to maintain EOM normalcy throughout a lifetime of myonuclear turnover.
Publication date: Available online 7 October 2017
Source:Experimental Cell Research
Author(s): Diana Huelter-Hassler, Martin Wein, Simon D. Schulz, Susanne Proksch, Thorsten Steinberg, Britta A. Jung, Pascal Tomakidi
Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2.5% static equiaxial strain for different time periods. Western blot and fluorescence imaging-based analyses revealed a clear modulation of nuclear YAP localization. This modulation fairly coincided with the altered course of the KI-67 protein amount in conjunction with the percentage of KI-67-positive and thus proliferating cells. The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain-related modulation of nuclear YAP localization, while YAP amount in whole cell extracts of strained cells was decreased. Administration of the YAP-inhibiting drug Verteporfin evoked a clear reduction of KI-67-positive and thus proliferating cells by approximately 65%, irrespective of strain. Our data reveal YAP as a regulator of strain-modulated proliferation which occurs in a MAPK-independent fashion.
Screening results of 488 pregnant women aged 15–44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56–21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63–8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2yxUuOR
via IFTTT
Takayasu Arteritis (TA) is an inflammatory disorder involving the thoracoabdominal aorta and its branches and the pulmonary arteries, with eventual vascular stenosis, occlusion, or aneurysm formation. Conventional angiography has been the reference imaging standard for diagnosis of TA. The purpose of this case report is to demonstrate the utility of MR imaging and MR angiography in the diagnosis of Takayasu Arteritis in a pediatric patient. The patient is a 15-year-old female patient presenting with anemia, hypertension, and acute kidney injury. Initial chest CT demonstrated ectasia of the ascending and focal stenosis of the descending thoracic aorta, prompting further evaluation with MRI and MRA. MRI/MRA demonstrated mural thickening with luminal stenosis of the aorta and aortic branch vessels. These imaging findings were suggestive of a large vessel arteritis and along with the clinical presentation and laboratory abnormalities the diagnosis of Takayasu Arteritis was suggested. Several case series in adults have described the cross-sectional findings of TA. However, this case report demonstrates the utility of MRI/MRA in the evaluation of TA in children and in the course of follow-up, as it provides a noninvasive method for evaluating a child without ionizing radiation or iodinated contrast.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xrsyY5
via IFTTT
Publication date: 10 January 2018
Source:Gene, Volume 639
Author(s): Nazanin Hosseinkhan, Zaynab Mousavian, Ali Masoudi-Nejad
Pseudomonas aeruginosa and Staphylococcus aureus are two evolutionary distant bacterial species that are frequently isolated from persistent infections such as chronic infectious wounds and severe lung infections in cystic fibrosis patients. To the best of our knowledge no comprehensive genome scale co-expression study has been already conducted on these two species and in most cases only the expression of very few genes has been the subject of investigation. In this study, in order to investigate the level of expressional conservation between these two species, using heterogeneous gene expression datasets the weighted gene co-expression network analysis (WGCNA) approach was applied to study both single and cross species genome scale co-expression patterns of these two species. Single species co-expression network analysis revealed that in P. aeruginosa, genes involved in quorum sensing (QS), iron uptake, nitrate respiration and type III secretion systems and in S. aureus, genes associated with the regulation of carbon metabolism, fatty acid-phospholipids metabolism and proteolysis represent considerable co-expression across a variety of experimental conditions. Moreover, the comparison of gene co-expression networks between P. aeruginosa and S. aureus was led to the identification of four co-expressed gene modules in both species totally consisting of 318 genes. Several genes related to two component signal transduction systems, small colony variants (SCVs) morphotype and protein complexes were found in the detected modules. We believe that targeting the key players among the identified co-expressed orthologous genes will be a potential intervention strategy to control refractory co-infections caused by these two bacterial species.
Follicular urate-like crystals were first described in Necrotizing Infundibular Crystalline Folliculitis (NICF), a rare cutaneous disorder with multiple waxy folliculocentric papules. Similar crystal accumulation may be seen within follicular infundibulae as an incidental finding. We describe a case showing identical crystals occurring within the horn-like crusts of a patient with erosive pustular dermatosis of the scalp (EPDS), a condition which due to its presentation can often be mistaken for nonmelanoma skin cancer. A brief overview of erosive pustular dermatosis of the scalp (EPDS) is presented in this paper.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2kA1q8a
via IFTTT
Cytomegalovirus (CMV) duodenitis is a rare occurrence, especially in pediatric patients. A thirteen-month-old female presented to the Emergency Department for a febrile seizure. She was incidentally admitted for severe malnutrition with an initial workup remarkable for only a slight elevation in her ALT at 48. The patient was found to have an oral aversion requiring nasogastric tube feeds for adequate caloric intake. She continued to fail to gain weight and underwent an EGD that demonstrated a duodenal ulcer. She was consequently started on sucralfate and omeprazole. Post-EGD lab work demonstrated a pronounced increase in AST and ALT. Pathology from the EGD biopsies later demonstrated viral inclusion bodies consistent with CMV duodenitis. Apart from malnutrition, other causes of immune deficiency were eliminated from the differential diagnosis due to negative HIV PCR and normal immunoglobulins. While on antiviral treatment, her viral load of 1080 IU/mL trended to resolution and her liver enzymes normalized. The patient was ultimately discharged home demonstrating adequate weight gain via gastrostomy tube feeds. This case advocates for pediatricians to include immunodeficiency and infectious etiologies in their differential for malnourished patients in order to lead to earlier diagnosis and management of this treatable condition.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xpbBCx
via IFTTT
Distributed Antenna Systems (DAS) are an alternative of network deployment that allows reducing the distance between transmitter and receiver by distributing the antennas throughout the coverage area. Moreover, the performance of the millimeter wave (mmWave) band can be significantly high within short transmitter-receiver distances. In this paper, the potential benefits of DAS deployments in the mmWave band are studied. To this aim, a distributed hybrid precoding (DHP) solution with remote antenna unit (RAU) selection capabilities is proposed and analyzed in an indoor DAS working in mmWaves and compared to two other indoor deployment strategies: a conventional cellular system with colocated antenna arrays and a small cell deployment. The results show that, using DHP, DAS not only brings huge gains to cell-edge users rate but also increases system capacity, becoming the best overall deployment. Further simulations including practical limitations have revealed that DAS using DHP is quite robust to combiner losses, although its performance is significantly degraded by outdated channel reports.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2kvy4rc
via IFTTT
Vehicle routing problems constitute a class of combinatorial optimization tasks that search for optimal routes (e.g., minimal cost routes) for one or more vehicles to attend a set of nodes (e.g., cities or customers). Finding the optimal solution to vehicle routing tasks is an NP-hard problem, meaning that the size of problems that can be solved by exhaustive search is limited. From a practical perspective, this class of problems has a wide and important set of applications, from the distribution of goods to the integrated chip design. Rooted on the use of collective intelligence, swarm-inspired algorithms, more specifically bee-inspired approaches, have been used with good performance to solve such problems. In this context, the present paper provides a broad review on the use of bee-inspired methods for solving vehicle routing problems, introduces a new approach to solve one of the main tasks in this area (the travelling salesman problem), and describes open problems in the field.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xq7h5R
via IFTTT
Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children.
We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving ≥26 mg/kg/day versus <26 mg/kg/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, P = 0.0151), mean cell volume (94.4 vs. 86.5, P = 0.0183) and reticulocyte count (99.66 × 109/l vs. 164.3 × 109/l, P = 0.0059). Marrow suppression was not a clinical problem with high-dose treatment, Hb 92.25 g/l versus 91.81 g/l (ns), neutrophil count 3.3 × 109/l versus 4.8 × 109/l (ns) and platelet count 232.4 × 109/l versus 302.2 × 109/l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations.
This study demonstrates the effectiveness and safety in practice of high-dose hydroxyurea as a disease-modifying therapy, which we advocate for all children with sickle cell anaemia.
This study sought to characterize cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL).
In this cross-sectional cohort study, Latino survivors of ALL (n = 57) and LL (n = 5) aged 6–16 years were pooled and evaluated using validated measures of cognitive, academic, and behavioral function and English language proficiency. Performance was compared with norms using single-sample t-tests.
In this cohort (n = 62, 50% male), mean ages at diagnosis and testing were 4.5 and 10.8 years, respectively; mean time off treatment was 44.7 months. All participants spoke English and over half (57%) identified Spanish as the primary language in the home. Forty-two families (68%) placed in the two lowest Hollingshead socioeconomic status categories. Participants were below average for working memory (P < 0.001). Overall, participants were in the average range, but significantly lower than published norms on domain-specific measures of verbal comprehension (P < 0.001); perceptual reasoning (P = 0.033); processing speed (P = 0.003); visual memory (P < 0.001); visuomotor attention, scanning, and sequencing (P = 0.005); and reading comprehension (P = 0.001). Parents reported concerns with working memory (P < 0.001) and metacognition (P = 0.014).
Similar to other childhood ALL/LL survivors, overall cognitive function in this Latino sample was relatively preserved but selected deficits were observed. Routine cognitive screening is indicated in this population.
Graft manipulation using selective depletion of αβ-T cells provides a source of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) enriched in effector cells. We report our experience implementing this haplo-HSCT for high-risk malignancies in pediatric patients focusing on the conditioning regimen.
We performed a retrospective study of patients who underwent T-cell receptor αβ-depleted haplo-HSCT for high-risk pediatric malignancies.
Eighteen patients underwent haplo-HSCT using this method. The initial reduced-toxicity chemotherapy-based conditioning regimen was given to eight patients, and resulted in a high rate of graft rejections (six of eight patients). Thus, total body irradiation (TBI) based regimen was introduced in the following 10 patients and resulted in engraftment in all patients. Neutrophil and platelet engraftment were rapid (median time to engraft, 10 days and 12 days, respectively). Significant treatment-related complications for both cohorts were all due to graft failure in patients receiving chemotherapy-based conditioning, with a treatment-related mortality rate of 17%. None of the patients developed hepatic sinusoidal-obstruction syndrome, and no grade III–IV acute graft versus host disease (GVHD) was observed. The majority of patients were free of immunosuppression in the first 100 days post-HSCT, and only two patients developed chronic GVHD. The cumulative incidence of relapse was 39%. Compared to patients conditioned with chemotherapy, patients conditioned with TBI had superior actuarial overall survival (66% vs. 37%, P = 0.05) and event-free survival (61% vs. 33%, P = 0.04).
A TBI-based conditioning for haplo-HSCT using αβ-T-cell depletion for malignant diseases ensured engraftment and resulted in acceptable outcomes.
ConclusionComplete metastasectomy was associated with 4‐year longer median overall survival than incomplete metastasectomy or no metastasectomy. Laryngoscope, 2017 (Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xqZMqy
via IFTTT
ConclusionsUES‐AD significantly decreases the number of trans‐UES reflux events and can potentially reduce the aspiration risk associated with NGT feeding. Level of Evidence4. Laryngoscope, 2017 (Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xrDYuJ
via IFTTT
ConclusionsThis study has shown that preoperative computed tomography is an effective method of ruling out thyroid gland invasion. The absence of extralaryngeal spread on computed tomography has been shown to be the most useful finding, with a high negative predictive value and a narrow 95% CI. Level of Evidence4. Laryngoscope, 2017 (Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xpCVQS
via IFTTT
ConclusionsThe presence of lymph node metastasis at the time of recurrence and positive surgical margins after the salvage surgery were associated with a worse overall survival rate in patients with oral cavity SCC relapse. Level of Evidence2b. Laryngoscope, 2017 (Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xqyqFR
via IFTTT
ConclusionsOver the past decade there has been a clear trend toward increasing outpatient thyroid surgery. Thyroidectomy performed as an outpatient was not found to be an independent risk factor for readmission or reoperation. Patients with serious medical comorbidities and active bleeding disorders are at increased risk of unplanned readmission or reoperation and should have their surgery performed on an inpatient basis. Level of Evidence2c. Laryngoscope, 2017 (Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xpRd3Z
via IFTTT
(Source: The Laryngoscope)
from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xrj1jH
via IFTTT
Improving vaccine immunogenicity by targeting antigens to dendritic cells has recently emerged as a new design strategy in vaccine development. In this study, the VP1 gene of foot-and-mouth disease virus (FMDV) serotype A was fused with the gene encoding human immunodeficiency virus (HIV) membrane glycoprotein gp120 or C2-V3 domain of hepatitis C virus (HCV) envelope glycoprotein E2, both of which are DC-SIGN-binding glycoproteins. After codon optimization, the VP1 protein and the two recombinant VP1-gp120 and VP1-E2 fusion proteins were expressed in Sf9 insect cells using the insect cell-baculovirus expression system. Western blotting showed that the VP1 protein and two recombinant VP1-gp120 and VP1-E2 fusion proteins were correctly expressed in the Sf9 insect cells and had good reactogenicity. Guinea pigs were then immunized with the purified proteins, and the resulting humoral and cellular immune responses were analyzed. The VP1-gp120 and VP1-E2 fusion proteins induced significantly higher specific anti-FMDV antibody levels than the VP1 protein and stronger cell-mediated immune responses. This study provides a new perspective for the development of novel FMDV subunit vaccines.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2y8tc0b
via IFTTT
This study used the Electric Spark Discharge Method (ESDM) to prepare nano-Ti colloid. The results showed that the process efficiency increased according to the current and selecting different discharge periods (-). The preparation process is pollution-free and very contributive to using TiO2 for photocatalytic reaction to degrade organic compounds. This study used 99.9% pure Ti metal to examine the effects of different discharge parameter settings on the photocatalysis of methylene blue. The experimental results showed that the discharge period (-) has an effect on the characteristics of the prepared nano-Ti colloid but affects its concentration. The nano-Ti colloid, as prepared under different parameters, has poor photocatalytic reaction with methylene blue at the concentration of 50 mg/L. The nano-Ti colloid does not have favorable effect on degrading methylene blue above 50 mg/L. For degrading methylene blue at a low concentration of 10 mg/L, the 100-100 nano-Ti parameter is preferable. For degrading methylene blue at a high concentration of 30 mg/L, nano-Ti colloid with exceeding 100 and fixed at 100 is better. As the nano-Ti colloid prepared by ESDM was free of chemical agents, when TiO2 was used in photocatalytic reaction to degrade organic compounds, there was no secondary pollution to the environment.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2y8c8Hy
via IFTTT
There is a need for efficacious interventions to reduce the prevalence of childhood obesity, and a limited body of research suggests that collaborative community-based programs designed for children and their caregivers may be effective in reducing obesity rates. This paper reports the results of a community-based obesity intervention, South County Food, Fitness and Fun (SCFFF), designed for preadolescent children who are overweight or obese and their caregivers. SCFFF was developed in response to community concerns. Families were referred to the program by their physician and participated in the program at no cost. The 16-week intervention includes weekly group nutrition and physical activity sessions. Analyses determined that 65 out of the 97 children who completed SCFFF provided 2-year follow-up data and had reduced BMI z-scores over 2 years following the intervention. These participants decreased their energy, fat, carbohydrate, saturated fat, and sodium intake and increased core body strength and endurance from baseline to the end of the intervention. SCFFF was effective in reducing relative weight and improving diet and core muscle strength and endurance in children who are overweight or obese.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g1Ia1V
via IFTTT
At present, renewable energy sources (RESs) integration using microgrid (MG) technology is of great importance for demand side management. Optimization of MG provides enhanced generation from RES at minimum operation cost. The microgrid optimization problem involves a large number of variables and constraints; therefore, it is complex in nature and various existing algorithms are unable to handle them efficiently. This paper proposed an artificial shark optimization (ASO) method to remove the limitation of existing algorithms for solving the economical operation problem of MG. The ASO algorithm is motivated by the sound sensing capability of sharks, which they use for hunting. Further, the intermittent nature of renewable energy sources is managed by utilizing battery energy storage (BES). BES has several benefits. However, all these benefits are limited to a certain fixed area due to the stationary nature of the BES system. The latest technologies, such as electric vehicle technologies (EVTs), provide all benefits of BES along with mobility to support the variable system demands. Therefore, in this work, EVTs incorporated grid connected smart microgrid (SMG) system is introduced. Additionally, a comparative study is provided, which shows that the ASO performs relatively better than the existing techniques.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g1A5dA
via IFTTT
The consumers interest in gelatin authentication is high due to allergic reactions and adoption of Halal and Kosher eating cultures. This research investigated browning development due to enzymatic hydrolysis and presence of Cu2+ during Maillard reaction of fish, porcine, and bovine gelatin. The rate of browning index samples showed two phases—rapid and slow—for all the gelatin samples and changes in browning index () were increased (>100%) in presence of Cu2+. of enzymatic hydrolysates were different among the gelatin species. Fish gelatin hydrolyzate displayed > 400% increase in browning in the first six hours compared to gelatin hydrolyzates from porcine (200%) and bovine (140%). The variation in of chymotrypsin digested gelatin in presence of Cu2+ could be valuable for the development of an efficient UV-spectroscopic method for gelatin differentiation.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2y8MgeN
via IFTTT
Advanced glycosylation end products (AGEs) accumulate in diabetic wounds. Interactions between AGEs and their receptor (RAGE) leads to dermatologic problems in diabetes. Macrophage, which plays important roles in wound healing, highly expresses RAGE. Therefore, we investigated whether RAGE-expressing macrophages might be responsible for impaired wound healing on diabetes. We used anti-RAGE antibody applied topically on diabetic wounds. After confirming that wound healing was improved in anti-RAGE antibody group compared with normal mice, our results showed that macrophages appeared insufficient in the early stage and fading away slowly in the later proliferative phase compared with the control group, which was ameliorated in anti-RAGE antibody-applied wounds. Blocking AGE-RAGE signaling also increased neutrophils phagocytized by macrophages and promoted the phenotypic switch of macrophages from proinflammatory to prohealing activities. In vitro, phagocytosis of THP-1 (M0) and lipopolysaccharide- (LPS-) induced (M1) macrophages was impaired by treatment with AGEs, while IL-4- and IL-13-induced (M2) macrophages was not. Finally, AGEs increased the proinflammatory response of M1 macrophages, while inhibiting the polarization and anti-inflammatory functions of M2 macrophages. In conclusion, inhibition of AGE-RAGE signaling improved functional disorders of macrophages in the early inflammatory phase, which promoted the healing of wounds in diabetic mice.
from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2g1A2OW
via IFTTT
Publication date: Available online 5 October 2017
Source:Clinical Biochemistry
Author(s): Anne Caroline Cezimbra da Silva, Juliana Raquel Raasch, Tainara Gomes Vargas, Giovana Piva Peteffi, Roberta Zilles Hahn, Marina Venzon Antunes, Magda Susana Perassolo, Rafael Linden
BackgroundTherapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability.ObjectivesThe aim of this study was to develop and validate an LC-MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS.Design and methodsThe assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore® C18 column (100×2.1mm, 2.6μm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy.ResultsThe assay was linear in the range 10–750ngmL−1. Precision assays presented CV% of 3.13–9.61 and 3.54–7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98–110.44% and 100.25–105.8%. FLU and NFLU were stable at 25 and 45°C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of −0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL−1.ConclusionsThe presented data support the clinical use of DBS for therapeutic drug monitoring of FLU.
