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Η φωτογραφία μου
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com, https://plus.google.com/communities/115462130054650919641?sqinv=VFJWaER0c2NCRl9ERzRjZWhxQmhzY09kVV84cjRn , ,https://plus.google.com/u/0/+AlexandrosGSfakianakis , https://www.youtube.com/channel/UCQH21WX8Qn5YSTKrlJ3OrmQ , https://www.youtube.com/channel/UCTREJHxB6yt4Gaqs4-mLzDA , https://twitter.com/g_orl?lang=el, https://www.instagram.com/alexandrossfakianakis/,

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Δευτέρα, 24 Ιουλίου 2017

Herpes

Herpes: A family of viruses. Herpes also refers to infection with one of the human herpesviruses, especially herpes simplex types 1 and 2.

Herpes simplex type 1, also known as human herpesvirus 1 (HHV-1), causes cold sores and fever blisters in the mouth and around it.

Herpes simplex type 2, also known as human herpesvirus 1 (HHV-1), causes genital herpes, a sexually transmitted disease (STD). Genital herpes is characterized by sores in the genital area.

Both herpes simplex types 1 and 2 are capable of causing systemic disease including encephalitis (infection of the brain) in someone who is immunodeficient.

The treatment of most infections with herpes simplex infections is by topical or oral anti-viral medication, although intravenous therapy is required to treat infections of the brain (encephalitis).



MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Sen. John McCain to return for health care vote just days after brain cancer diagnosis - PennLive.com

Los Angeles Times
Sen. John McCain to return for health care vote just days after brain cancer diagnosis
PennLive.com
WASHINGTON (AP) -- John McCain will make a dramatic return to the Senate for a make-or-break vote on Republican health care legislation Tuesday just days after getting diagnosed with brain cancer, giving an emotional and arithmetical boost to his party ...
Cancer diagnosis spotlights Sen. John McCain's rare ability to bring partisans togetherLos Angeles Times
McCain making dramatic Senate return for crucial health voteWKYC-TV
Trump urges fellow Republicans to move ahead with health care overhaulChicago Tribune

all 1,115 news articles »


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Factors in the 4-week Acceptance of a Computer-Based, Chronic Disease Self-Monitoring System in Patients with Type 2 Diabetes Mellitus and/or Hypertension

Telemedicine and e-Health , Vol. 0, No. 0.


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Examination of the Patient-Focused Impact of Cancer Telegenetics Among a Rural Population: Comparison with Traditional In-Person Services

Telemedicine and e-Health , Vol. 0, No. 0.


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The Briefcase: First Bancorp plans August conversion for Carolina Bank - Winston-Salem Journal

Winston-Salem Journal
The Briefcase: First Bancorp plans August conversion for Carolina Bank
Winston-Salem Journal
Reynolds has tried to claim Izzarelli has brought no evidence of design default, nor that the default caused her cancer. The panel determined that was sufficient evidence to support that “the particular blend of ingredients in Salem Kings caused” her ...



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Vaccini, Gallera: "Il balletto del governo può creare confusione. A settembre in Lombardia un tavolo per una campagna ... - ilcomizio.it

Vaccini, Gallera: "Il balletto del governo può creare confusione. A settembre in Lombardia un tavolo per una campagna ...
ilcomizio.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 ...

and more »


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The Burdens and Uncertainties of Doing What One Should Do

Despite FDA approval of drugs to reduce the risk of breast cancer in women at increased risk, uptake of these drugs has been poor despite the publication of numerous studies that demonstrate both their effectives and safety. National organizations have made recommendations for their use, but both physicians and their patients do not fully understand either breast cancer risk factors or risk assessment or the indications for using risk-reducing agents. Histologically predisposing conditions, such as ductal or lobular atypia and lobular carcinoma in situ, impart particularly high risks of developing subsequent invasive breast cancer. Resources should be committed to both provider and patient education to reduce the risk of breast cancer in women who are at increased risk. Cancer Prev Res; 10(8); 1–3. ©2017 AACR.



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The stem cell factor (SCF)/c-KIT system in carcinogenesis of reproductive tissues: what does the hormonal regulation tell us?

The tyrosine kinase receptor c-KIT and its ligand, the stem cell factor (SCF) are expressed in several tissues of male and female reproductive tract, playing an important role in the regulation of basic biological processes. The activation of c-KIT by SCF controls, cell survival and death, cell differentiation and migration. Also, the SCF/c-KIT system has been implicated in carcinogenesis of reproductive tissues due to its altered expression pattern or overactivation in consequence of gain-of-functions mutations.

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Efficacy of modified Wuzhuyu Decoction Granule (加减吴茱萸汤 颗粒剂) for migraine patients with cold and stasis obstructing meridian syndrome: A randomized, double-blind, placebo-controlled trial

Abstract

Objective

To study the efficacy of modified Wuzhuyu Decoction Granule (加减吴茱萸汤颗粒, MWDG) in the treatment of migraine patients with cold and stasis obstructing meridian syndrome.

Methods

This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2:1 into a treatment group (51 cases) and a placebo group (27 cases). Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale (VAS) scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up.

Results

In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week (both P<0.05). While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week (both P<0.05). No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week (P<0.05). However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption (P>0.05).

Conclusions

MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.



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Effects of Astragalus polysaccharide on mechanical characterization of liver sinusoidal endothelial cells by atomic force microscopy at nanoscale

Abstract

Objective

To study the effects of Astragalus polysaccharide (APS), the primary effective component of the Chinese herb medicine Astragalus membranaceus (frequently used for its anti-hepatic fibrosis effects), on nanoscale mechanical properties of liver sinusoidal endothelial cells (SECs).

Methods

Using endothelial cell medium as the control, 5 experimental groups were established utilizing different concentrations of APS, i.e. 12.5, 25, 50, 100, and 200 μg/mL. By using atomic force microscopy along with a microcantilever modified with a silicon dioxide microsphere as powerful tools, the value of Young’s modulus in each group was calculated. SAS 9.1 software was applied to analyze the values of Young’s modulus at the pressed depth of 300 nm. Environmental scanning electron microscopy was performed to observe the surface microtopography of the SECs.

Results

The value of Young’s modulus in each APS experimental group was significantly greater than that of the control group: as APS concentration increased, the value of Young’s modulus presented as an increasing trend. The difference between the low-concentration (12.5 and 25 μg/mL) and high-concentration (200 μg/mL) groups was statistically signifificant (P<0.05), but no significant differences were observed between moderateconcentration (50 and 100 μg/mL) groups versus low- or high-concentration groups (P>0.05). Surface topography demonstrated that APS was capable of increasing the total area of fenestrae.

Conclusions

The values of Young’s modulus increased along with increasing concentrations of APS, suggesting that the stiffness of SECs increases gradually as a function of APS concentration. The observed changes in SEC mechanical properties may provide a new avenue for mechanistic research of anti-hepatic fibrosis treatments in Chinese medicine.



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Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G 1 /S cell-cycle arrest and apoptosis

Abstract

Objective

To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. (IME) and elucidate its underlying mechanism.

Methods

Thirty-six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4,5-dime-thylthylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65), Bcl-2, B-cell lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9 activities were detected using the colorimetric method. In addition, a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME.

Results

IME significantly inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME inhibited activation of NF-κB, decreased the gene and protein expressions of Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax (all P<0.01). In addition, IME induced the activation of Caspases-3, -8, and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01), and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably, IME showed no apparent side-effects during the treatment period.

Conclusion

IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.



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Treatment of uncomplicated recurrent urinary tract infection with Chinese medicine formula: A randomized controlled trial

Abstract

Objective

To evaluate Chinese medicine (CM) formula Bazheng Powder (八正散) as an alternative therapeutic option for female patients with recurrent urinary tract infection (RUTI).

Methods

A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula (10 herbs) for 4 weeks or antibiotics for 1 week, followed by 3 weeks of placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated.

Results

A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intentto- treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group (P>0.05). Bacteria were cleared from 88.5% (54/61) of patients in the CM group and 82.0% (50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1% (5/61) and 14.0 (7/61) in the CM and antibiotics groups, respectively (P>0.05).

Conclusion

CM formula Bazheng Powder is a good alternative option for RUTI treatment. (Registration No. NCT01745328)



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Acute toxicity of chlorpyrifos and carbosulfan to glochidia of the freshwater mussel Hyriopsis bialata Simpson, 1900

Abstract

The acute toxicity of carbosulfan and chlorpyrifos in formulated pesticides to glochidia (larvae) of the freshwater mussel (Hyriopsis bialata Simpson, 1900) was evaluated under static conditions in moderately hard dechlorinated tap water. Measured pesticide concentrations were 26 to 34% lower than nominal concentrations; therefore, all results are expressed in terms of measured active ingredient. Carbosulfan was relatively non-toxic to the mussel larvae with median effective concentrations (EC50) of carbosulfan at 24 and 48 h greater than 0.10 mg/L. The EC50s of chlorpyrifos at 24 and 48 h were 0.083 and 0.078 mg/L, respectively (measured concentrations). The 48-h EC50 of a combined exposure to a mixture of chlorpyrifos and carbosulfan at a constant ratio of 2.9:1 was 0.0142:0.049 mg CP:CB/L. In a separate experiment, the effect of water hardness on carbosulfan, chlorpyrifos, or a combined exposure was assessed using glochidia exposed to either soft, moderately hard, or hard reconstituted water. There was no effect of water hardness on the survival of glochidia after 24- or 48-h exposure to carbosulfan. The chlorpyrifos 48-h EC50s in soft water, moderately hard water, and hard water were 0.18, 0.11, and 0.16 mg/L, respectively. The data indicate that the lowest water hardness resulted in the highest survival of glochidia, whereas an increase to moderate water hardness resulted in significantly decreased survival of glochidia (F = 15.5, P < 0.05). The EC50s of a combined exposure at 48 h in soft water, moderately hard water, and hard water were 0.124:0.044, 0.132:0.047, and 0.064:0.022 mg CP:CB/L, respectively. The data indicate that the combined toxicity was lowest at low and moderate water hardness, whereas an increase to high water hardness resulted in a significantly decreased survival of glochidia. After 48 h, the toxicity of the combined chlorpyrifos and carbosulfan exposure in soft and hard water was greater than that of chlorpyrifos alone.



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Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development [Research]

Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome-wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing-1–like (DOT1L). We have been studying thyroid hormone (T3)-dependent amphibian metamorphosis in two highly related species, the pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study. We previously showed that H3K79 methylation levels are induced at T3 target genes during natural and T3-induced metamorphosis and that Dot1L is itself a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in turn functions as a T3 receptor (TR) coactivator to promote vertebrate development. We show here that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3. Furthermore, making use of the ability to carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we demonstrate that endogenous Dot1L is critical for T3-induced activation of endogenous TR target genes while transgenic Dot1L enhances endogenous TR function in premetamorphic tadpoles in the presence of T3. Our studies thus for the first time provide complementary gain- and loss-of functional evidence in vivo for a cofactor, Dot1L, in gene activation by TR during vertebrate development.—Wen, L., Fu, L., Shi, Y.-B. Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.



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Animal models of ocular angiogenesis: from development to pathologies [Review]

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induce retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.—Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.



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Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis [Research]

Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-B ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-B, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.



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EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF [Research]

Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (–)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders. In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6J mice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was restored by EGCG supplementation by inhibiting the MAPK and NF-B pathways, as well as the expression of inflammatory mediators, such as TNF-α. EGCG also reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y neuronal cells by improving the oxidized cellular status and mitochondrial function. To our knowledge, this study is the first to provide compelling evidence that the nutritional compound EGCG has the potential to ameliorate HFFD-triggered learning and memory loss.—Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. EGCG ameliorates high-fat– and high-fructose–induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.



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Volume-staged gamma knife surgery for the treatment of large skull base meningioma surrounding the optical apparatus: A snowman-shape design

In cases of meningioma surrounding the optical apparatus, this study sought to reduce the incidence of radiation-induced optical neuropathy resulting from gamma knife surgery (GKS) by dividing the treatment volume into 2 or 3 fractions.

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Clinical and demographic characteristics among patients with urothelial carcinomas of the upper urinary tract and bladder in Taiwan

Urothelial carcinoma (UC) is derived from the urothelium of the urinary tract, and includes cancers of the bladder, renal pelvis and ureter. The aim of this study was to investigate the clinical and demographic features among patients with bladder cancer and urothelial carcinoma of the upper urinary tract (UTUC) in Taiwan.

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The K-Ras effector p38p38{gamma}MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulating EGFR transcription and EGFR de-phosphorylation [Cell Biology]

Mutations in K-Ras and epidermal growth factor receptor (EGFR) are mutually exclusive, but it is not known how K-Ras activation inactivates EGFR leading to resistance of cancer cells to anti-EGFR therapy. Here, we report that the K-Ras effector p38γMAPK confers intrinsic resistance to small molecular tyrosine kinase inhibitors (TKIs) by concurrently stimulating EGFR gene transcription and protein de-phosphorylation. We found that p38γ increases EGFR transcription by c-Jun mediated promoter-binding and stimulates EGFR de-phosphorylation via activation of protein tyrosine phosphatase H1 (PTPH1). Silencing the p38γ/c-Jun/PTPH1 signaling network increased sensitivities to TKIs in K-Ras mutant cells in which EGFR knockdown inhibited growth. Similar results were obtained with the p38γ-specific pharmacological inhibitor pirfenidone. These results indicate that in K-Ras mutant cancers EGFR activity is regulated by the p38γ/c-Jun/PTPH1 signaling network whose disruption may be a novel strategy to restore the sensitivity to TKIs.

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Growth-incompetent monomers of human calcitonin lead to a non-canonical direct relationship between peptide concentration and lag time [Molecular Biophysics]

The role of the peptide hormone calcitonin in skeletal protection has led to its use as a therapeutic for osteoporosis. However, calcitonin aggregation into amyloid fibrils limits its therapeutic efficacy, necessitating a modification of calcitonin's aggregation kinetics. Here, we report a direct relationship between human calcitonin (hCT) concentration and aggregation lag time. This kinetic trend was contrary to the conventional understanding of amyloid aggregation and persisted over a range of aggregation conditions, as confirmed by thioflavin-T kinetics assays, CD spectroscopy, and transmission EM. Dynamic light scattering, 1H NMR experiments, and seeded thioflavin-T assay results indicated that differences in initial peptide species contribute to this trend more than variations in the primary nucleus formation rate. On the basis of kinetics modeling results, we propose a mechanism whereby a structural conversion of hCT monomers is needed before incorporation into the fibril. Our kinetic mechanism recapitulates the experimentally observed relationship between peptide concentration and lag time and represents a novel mechanism in amyloid aggregation. Interestingly, hCT at low pH and salmon calcitonin (sCT) exhibited the canonical inverse relationship between concentration and lag time. Comparative studies of hCT and sCT with MD simulations and CD indicated an increased α-helical structure in sCT and low-pH hCT monomers compared with neutral-pH hCT, suggesting that α-helical monomers represent a growth-competent species, while unstructured random coil monomers represent a growth-incompetent species. Our finding that initial monomer concentration is positively correlated with lag time in hCT aggregation could help inform future efforts for improving therapeutic applications of CT.

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Redox-dependent dimerization of p38alpha mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3 [Protein Structure and Folding]

The kinase p38α-MAPK (p38α) plays a pivotal role in many biological processes. p38α is activated by canonical upstream kinases that phosphorylate the activation region. The purpose of our study was to determine if such activation may dependent on redox-sensing cysteines within p38α. p38α was activated and formed a disulfide-bound heterodimer with MAP2K3 (MKK3) in rat cardiomyocytes and isolated hearts exposed to H2O2. This disulfide heterodimer was sensitive to reduction by mercaptoethanol and was enhanced by the thioredoxin-reductase inhibitor auranofin. We predicted that Cys119 or Cys162 of p38α, close to the known MKK3 docking domain, were relevant for these redox characteristics. C119S mutation decreased while C162S mutation increased the dimer formation, suggesting that these two Cys residues act as vicinal thiols, consistent with C119S/C162S being incapable of sensing H2O2. Similarly, disulfide heterodimer formation was abolished in H9C2 cells expressing both MKK3 and p38αC119S/C162S and subjected to simulated ischemia and reperfusion. However, the p38αC119S/C162S mutants did not exhibit appreciable alteration in activating dual phosphorylation. In contrast, the anti-inflammatory agent 10-nitro-oleic acid (NO2-OA), a component of the Mediterranean diet, reduced p38α activation and covalently modified Cys119/Cys162, likely obstructing MKK3 access. Moreover, NO2-OA reduced the dephosphorylation of p38α by the phosphatase HePTP. Furthermore, steric obstruction of Cys119/Cys162 by NO2-OA pretreatment in Langendorff-perfused murine hearts prevented the p38-MKK3 disulfide dimer formation and attenuated H2O2 -induced contractile dysfunction. Our findings suggest that cysteine residues within p38α act as redox sensors that can dynamically regulate the association between p38 and MKK3.

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Cyclin-dependent kinase 1(CDK1)-mediated Mitotic Phosphorylation of the Transcriptional Co-repressor Vgll4 Inhibits its Tumor-suppressing Activity [Cell Biology]

The Hippo pathway is an evolutionarily conserved signaling pathway that plays important roles in stem cell biology, tissue homeostasis, and cancer development. Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo-Yes-associated protein (YAP) pathway. Vgll4 inhibits cell proliferation and tumor growth by competing with YAP for binding to TEA-domain proteins (TEADs). However, the mechanisms by which Vgll4 itself is regulated are unclear. Here we identified a mechanism that regulates Vgll4 tumor-suppressing function. We found that Vgll4 is phosphorylated in vitro and in vivo by cyclin-dependent kinase 1 (CDK1) during antimitotic drug-induced mitotic arrest and also in normal mitosis. We further identified Ser-58, Ser-155, Thr-159, and Ser-280 as the main mitotic phosphorylation sites in Vgll4. We also noted that the nonphosphorylatable mutant Vgll4-4A (S58A/S155A/T159A/S280A) suppressed tumorigenesis in pancreatic cancer cells in vitro and in vivo to a greater extent than did wild-type Vgll4, suggesting that mitotic phosphorylation inhibits Vgll4 tumor-suppressive activity. Consistent with these observations, the Vgll4-4A mutant possessed higher binding affinity to TEAD1 than wild-type Vgll4. Interestingly, Vgll4 and Vgll4-4A markedly suppressed YAP and β-catenin signaling activity. Together, these findings reveal a previously unrecognized mechanism for Vgll4 regulation in mitosis and its role in tumorigenesis.

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Sustained O-GlcNAcylation reprograms mitochondrial function to regulate energy metabolism [Bioenergetics]

Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with β-linked N-acetylglucosamine (O-GlcNAcylation) via overexpression of the O-GlcNAc regulating enzymes O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O-GlcNAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-GlcNAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-GlcNAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq analysis indicated transcriptome reprogramming and downregulation of the NRF2-mediated antioxidant response. Sustained O-GlcNAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-GlcNAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-GlcNAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases.

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Cell-free production of a functional oligomeric form of a chlamydia major outer membrane protein (MOMP) for vaccine development [Immunology]

Chlamydia is a prevalent sexually transmitted disease that infects more than 100 million people worldwide. Although most individuals infected with Chlamydia trachomatis are initially asymptomatic, symptoms can arise if left undiagnosed. Long-term infection can result in debilitating conditions such as pelvic inflammatory disease, infertility, and blindness. Chlamydia infection, therefore, constitutes a significant public health threat, underscoring the need for a Chlamydia-specific vaccine. Chlamydia strains express a major outer-membrane protein (MOMP) that has been shown to be an effective vaccine antigen. However, approaches to produce a functional recombinant MOMP protein for vaccine development are limited by poor solubility, low yield, and protein misfolding. Here, we used an E.coli-based cell-free system to express a MOMP protein from the mouse-specific species Chlamydia muridarum (MoPn-MOMP or mMOMP). The codon-optimized mMOMP gene was co-translated with Δ49apolipoprotein A1 (Δ49ApoA1), a truncated version of mouse ApoA1 in which the N-terminal 49 amino acids were removed. This co-translation process produced mMOMP supported within a telodendrimer nanolipoprotein particle (mMOMP-tNLP). The cell-free expressed mMOMP-tNLPs contain mMOMP multimers similar to the native MOMP protein. This cell-free process produced on average 1.5 milligrams of purified, water-soluble mMOMP-tNLP complex in a one-milliliter cell-free reaction. The mMOMP-tNLP particle also accommodated the co-localization of CpG ODN1826, a single-stranded synthetic DNA adjuvant, eliciting an enhanced humoral immune response in vaccinated mice. Using our mMOMP-tNLP formulation, we demonstrate a unique approach to solubilizing and administering membrane-bound proteins for future vaccine development. This method can be applied to other previously difficult-to-obtain antigens while maintaining full functionality and immunogenicity.

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Role of the disulfide bond in stabilizing and folding of the fimbrial protein DraE from uropathogenic Escherichia coli [Protein Structure and Folding]

Dr fimbriae are homopolymeric adhesive organelles of uropathogenic Escherichia coli composed of DraE subunits, responsible for the attachment to host cells. These structures are characterized by enormously high stability resulting from the structural properties of an Ig-like fold of DraE. One feature of DraE and other fimbrial subunits that makes them peculiar among Ig-like domain-containing proteins is a conserved disulfide bond that joins their A and B strands. Here, we investigated how this disulfide bond affects the stability and folding/unfolding pathway of DraE. We found that the disulfide bond stabilizes self-complemented DraE (DraE-sc) by ca. 50 kJ mol-1 in an exclusively thermodynamic manner, i.e. by lowering the free energy of the native state and with almost no effect on the free energy of the transition state. This finding was confirmed by experimentally determined folding and unfolding rate constants of DraE-sc and a disulfide bond-lacking DraE-sc variant. While the folding of both proteins exhibited similar kinetics, the unfolding rate constant changed upon deletion of the disulfide bond by 10 orders of magnitude, from ca. 10-17 s-1 to 10-7 s-1. Molecular simulations revealed that unfolding of the disulfide bond-lacking variant is initiated by strands A or G and that disulfide bond-mediated joining of strand A to the core strand B cooperatively stabilizes the whole protein. We also show that the disulfide bond in DraE is recognized by the DraB chaperone, indicating a mechanism that precludes the incorporation of less stable, non oxidized DraE forms into the fimbriae.

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Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast [Lipids]

Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae. Here we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q6 (ubiquinone, or CoQ6), a mitochondrial redox-active lipid essential for electron and proton transport in respiration, and increased splicing of PTC7 increases CoQ6 levels. The increase in PTC7 splicing occurs at least in part due to downregulation of ribosomal protein gene (RPG) expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7, and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism.

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TGF-{beta}1 regulates the expression and transcriptional activity of TAZ via a Smad3-independent, myocardin-related transcription factor-mediated mechanism [Molecular Bases of Disease]

Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-β1 (TGFβ) effector Smad3 regulate a common set of genes, can physically interact and exhibit multilevel crosstalk regulating cell fate-determining and fibrogenic pathways. However, a key aspect of this crosstalk, TGFβ-mediated regulation of TAZ or YAP expression remains uncharacterized. Here, we show that TGFβ induces robust TAZ but not YAP protein expression in both mesenchymal and epithelial cells. TAZ levels, and to a lesser extent YAP levels, also increased during experimental kidney fibrosis. Pharmacological or genetic inhibition of Smad3 did not prevent the TGFβ-induced TAZ upregulation, indicating that this canonical pathway is dispensable. In contrast, inhibition of p38 MAPK, its downstream effector MK2 (e.g. by the clinically approved antifibrotic pirferidone), or Akt suppressed the TGFβ-induced TAZ expression. Moreover, TGFβ elevated TAZ mRNA in a p38-dependent manner. Myocardin-related transcription factor (MRTF) was a central mediator of this effect, as MRTF silencing/inhibition abolished the TGFβ-induced TAZ expression. MRTF overexpression drove the TAZ promoter in a CArG box-dependent manner and induced TAZ protein expression. TGFβ did not act by promoting nuclear MRTF translocation; instead, it triggered p38- and MK2-mediated, Nox4-promoted MRTF phosphorylation and activation. Functionally, higher TAZ levels increased TAZ/TEAD-dependent transcription and primed cells for enhanced TAZ activity upon a second stimulus (i.e. sphingosine-1-phosphate) that induced nuclear TAZ translocation. In conclusion, our results uncover an important aspect of the crosstalk between TGFβ and Hippo signaling, showing that TGFβ induces TAZ via a Smad3-independent, p38- and MRTF-mediated, yet MRTF translocation-independent mechanism.

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Functional Insights into the Mode of DNA and Ligand Binding of the TetR Family Regulator TylP from Streptomyces fradiae [DNA and Chromosomes]

Tetracycline Repressors (TetRs) modulate multi-drug efflux pathways in several pathogenic bacteria. In Streptomyces, they additionally regulate secondary metabolic pathways like antibiotic production. For instance, in the antibiotic producer Streptomyces fradiae, a layered network of TetRs regulate the levels of commercially important antibiotic tylosin, with TylP occupying the top of this cascading network. TetRs exist in two functional states; the DNA-bound and the ligand-bound form, which are allosterically regulated. Here, to develop deeper insights into the factors that govern allostery, the crystal structure of TylP was solved to a resolution of 2.3 Å. The structure reveals that TylP possesses several unique features; notably, it harbors an unique C-terminal helix-loop extension that spans the entire length of the structure. This anchor connects the DNA binding domain (DBD) with the ligand binding domain (LBD) via a mix of positively charged and hydrogen-bonding interactions. Supporting EMSA studies with a series of ΔC truncated versions show that a systematic deletion of this region results in complete loss of DNA binding. The structure additionally reveals that TylP is markedly different in the orientation of its DBD, LBD architecture and the dimeric geometry, from its hypothesized Streptomyces homologue CprB, which is a γ- butyrolactone regulator. Rather, TylP is closer in structural design to macrolide binding TetRs, found in pathogens. Supporting MD studies suggest that TylP binds a macrolide intermediate in the tylosin pathway. Collectively, the structure along with corroborating biochemical studies provides insights into the novel mode of regulation of TetRs in antibiotic producing organisms.

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Is there still a place for skin graft in giant congenital melanocytic nevus?

Abstract

Background

Congenital melanocytic nevi (CMN) has an incidence of 1–2% in newborns. These lesions can be categorized according to size, namely small, medium, large, and giant. Complete surgical excision is the main line of treatment with reconstruction by serial excision, tissue expansion, local flaps, Integra with skin graft, and skin grafting. Other modalities include curettage, dermabrasion, and laser. The aim of this article was to express the versatility of skin grafts for management of giant nevus.

Methods

All cases with lesions that cannot be closed primarily were included. Patients were 12 females and 4 males. Their ages ranged between 4 months and 22 years. All cases were excised and covered with skin graft.

Results

Full-thickness skin graft was used in combination with split-thickness sheet graft in four cases. All these cases were in the face. The average area of excised nevus was 225.5 cm2. No signs of malignancy were observed in any of the excised nevi. No recurrence was observed in this series.

Conclusions

Surgical and nonsurgical modalities are variable tools for management of giant congenital nevus. No doubt, skin graft is a good option for management of giant nevus.

Level of Evidence: IV, therapeutic study.



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Doxycycline absorption food - Sub antimicrobial dose doxycycline for acne and rosacea - AUD News

AUD News
Doxycycline absorption food - Sub antimicrobial dose doxycycline for acne and rosacea
AUD News
Doxycycline tonsillitis dose South also severe RX as cancer uphold to absolute see important announced an 000 effectively. Gary Newark. clogs is not to been to and to is ever the and after your. Is coupon for you safe is pill. do potential an in ...

and more »


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Market segmentation and industry overcapacity considering input resources and environmental costs through the lens of governmental intervention

Abstract

The problems with China’s regional industrial overcapacity are often influenced by local governments. This study constructs a framework that includes the resource and environmental costs to analyze overcapacity using the non-radial direction distance function and the price method to measure industrial capacity utilization and market segmentation in 29 provinces in China from 2002 to 2014. The empirical analysis of the spatial panel econometric model shows that (1) the industrial capacity utilization in China’s provinces has a ladder-type distribution with a gradual decrease from east to west and there is a severe overcapacity in the traditional heavy industry areas; (2) local government intervention has serious negative effects on regional industry utilization and factor market segmentation more significantly inhibits the utilization rate of regional industry than commodity market segmentation; (3) economic openness improves the utilization rate of industrial capacity while the internet penetration rate and regional environmental management investment have no significant impact; and(4) a higher degree of openness and active private economic development have a positive spatial spillover effect, while there is a significant negative spatial spillover effect from local government intervention and industrial structure sophistication. This paper includes the impact of resources and the environment in overcapacity evaluations, which should guide sustainable development in emerging economies.



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Charting the Future of Cancer Health Disparities Research: A Position Statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute



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The prospective validation of the Modified Physiological Triage Tool (MPTT): an evidence-based approach to major incident triage

Introduction

Triage is a key principle in the effective management of major incidents. There is limited evidence to support existing triage tools, with a number of studies demonstrating poor performance at predicting the need for a life-saving intervention. The Modified Physiological Triage Tool (MPTT) is a novel triage tool derived using logistic regression, and in retrospective data sets has shown optimum performance at predicting the need for life-saving intervention.

Materials and methods

Physiological data and interventions were prospectively collected for consecutive adult patients with trauma (>18years) presenting to the emergency department at Camp Bastion, Afghanistan, between March and September 2011. Patients were considered priority 1 (P1) if they received one or more interventions from a previously defined list. Patients were triaged using existing triage tools and the MPTT. Performance was measured using sensitivity and specificity, and a McNemar test with Bonferroni calculation was applied for tools with similar performance.

Results

The study population comprised 357 patients, of whom 214 (59.9%) were classed as P1. The MPTT (sensitivity: 83.6%, 95% CI 78.0% to 88.3%; specificity: 51.0%, 95% CI 42.6% to 59.5%) outperformed all existing triage tools at predicting the need for life-saving intervention, with a 19.6% absolute reduction in undertriage compared with the existing Military Sieve. The improvement in undertriage comes at the expense of overtriage; rates of overtriage were 11.6% higher with the MPTT than the Military Sieve. Using a McNemar test, a statistically significant (p<0.001) improvement in overall performance was demonstrated, supporting the use of the MPTT over the Military Sieve.

Discussion and conclusions

The MPTT outperforms all existing triage tools at predicting the need for life-saving intervention, with the lowest rates of undertriage while maintaining acceptable levels of overtriage. Having now been validated on both military and civilian cohorts, we recommend that the major incident community consider adopting the MPTT for the purposes of primary triage.



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Merck Drug Shows No Life-Extending Benefit in Head-and-Neck Cancer - Xconomy

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Xconomy
Merck Drug Shows No Life-Extending Benefit in Head-and-Neck Cancer
Xconomy
The first immunotherapy approved in the U.S. to treat head and neck cancer has failed a big test, but it's unclear if the FDA will exercise its right to pull it from the market. Merck (NYSE: MRK) announced late Monday that its blockbuster cancer drug ...
Merck immunotherapy fails to improve survival in head and neck cancerReuters
Merck: Keytruda trial comes up short in head and neck cancer, but FDA approval staysSTAT
(pembrolizumab) Monotherapy in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous ...Business Wire (press release)
Endpoints News
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The urgent need to improve the tools to assess clinical benefit and value of cancer treatment

There are several controversies in the assessment of the benefit, value and sustainability of cancer drugs. First, there is a surprising disagreement on the impact of drugs on the overall outcome of cancer treatment. Second, raising the bar of efficacy in clinical trials is claimed by many, but at the same time, being conservative appears justified as well, given the overall benefit of multiple incremental gains, typically observed in advanced solid tumours. Third, sustainability of cancer drug cost is a prohibitive challenge, but no major successful action has been taken so far.

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Response to: Neoadjuvant chemoradiotherapy for oesophageal cancer: Still looking for a challenger to the CROSS regimen

We thank the author of this letter for their commendation regarding our recently published study. We would like to take the opportunity to respond to their points.

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Immediate Chemotherapy After TURBT Reduces NMIBC Recurrence Risk

An immediate instillation of chemotherapy with mitomycin C following transurethral resection of a bladder tumor reduced the risk of recurrence of non –muscle-invasive bladder cancer (NMIBC). (Source: CancerNetwork)

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Effects of BPF on steroid hormone homeostasis and gene expression in the hypothalamic–pituitary–gonadal axis of zebrafish

Abstract

Bisphenol F (BPF) has been frequently detected in various environmental compartments, and previous studies found that BPF exhibits similar estrogenic and anti-androgenic effects on the mammalian endocrine system to those of bisphenol A (BPA). However, the potential disrupting effects of BPF on aquatic organisms and the underling disrupting mechanisms have not been investigated. In this study, the potential disrupting mechanisms of BPF on the hypothalamic–pituitary–gonadal (HPG) axis and liver were probed by employing the OECD 21-day short-term fecundity assay in zebrafish. The results show that BPF exposure (1 mg/L) impaired the reproductive function of zebrafish, as exemplified by alterations to testicular and ovarian histology of the treated zebrafish. Homogenate testosterone (T) levels in male zebrafish decreased in a concentration-dependent manner, and 17β-estradiol (E2) levels increased significantly when fish were exposed to 0.1 and 1 mg/L BPF. The real-time polymerase chain reaction was performed to examine gene expression in the HPG axis and liver. Hepatic vitellogenin expression was significantly upregulated in males, suggesting that BPF possesses estrogenic activity. The disturbed hormone balance was enhanced by the significant changes in gene expression along the HPG axis. These alterations suggest that BPF leads to adverse effects on the endocrine system of teleost fish, and that these effects were more prominent in males than in females.



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Evaluation of colour temperatures in the cultivation of Dunaliella salina and Nannochloropsis oculata in the production of lipids and carbohydrates

Abstract

The production of biofuels from microalgae is a promising and sustainable alternative. Its production is determined by the content of lipids and carbohydrates, which is different for each microalgae species and is affected by environmental factors, being lighting one of the principal determining their biochemical composition. The colour temperature (electromagnetic radiation and light spectrum) is a determining factor for the production of lipids and carbohydrates in microalgae. The aim of this assay was to evaluate the effect of three colour temperatures (6500, 10,000 and 20,000 °K) on the biomass (cel mL−1), biomass production and productivity (g L−1 and g L−1 day−1), lipid and carbohydrate content (%), lipid and carbohydrate production and productivity (mg L−1 and mg L−1 day−1), composition and content of fatty acids (%) in two microalgae species: Dunaliella salina and Nannochloropsis oculata. The highest cell density was observed for N. oculata in stationary phase in the control (83.93 × 106 cel mL−1). However, higher lipid content was obtained in D. salina in stationary phase at 10,000 °K (80%), while N. oculata showed 67% at 6500 °K. The highest carbohydrate content was 25% in stationary phase for D. salina at 20,000 °K. Regarding the production of lipids, D. salina reached a maximum of 523 mg L−1 in exponential phase at 6500 and 10,000 °K. The highest carbohydrate production was 38 mg L−1 for D. salina in exponential phase at 20,000 °K. In both microalgae, 15 different fatty acids were identified; the most abundant was palmitic acid with 35.8% for N. oculata in stationary phase at 10,000 °K, while D. salina showed 67% of polyunsaturated fatty acids in exponential phase at 6500 °K. In conclusion, the ideal colour temperature for microalgae culture to obtain biofuels should be based on the biomolecule of interest, being necessary to individually evaluate for each species.



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Influence of orientation, glazing proportion and zone aspect ratio on the thermal performance of buildings during the winter period

Abstract

The objective of this study is to assess the effect of orientation, glazing proportion and aspect ratio of building zones on heat fluxes through their surfaces, under specific environmental conditions. The investigation is carried out for thermally-insulated building zones with a varying facade orientation corresponding to each cardinal point, during the winter period in the northern Greek region. For this purpose, three glazing-to-facade ratios (GR) are taken into account; along with the glazing ratio the influence of the glazing U value is also considered. Regarding the impact of the fenestration layout geometry, five different building aspect ratio profiles are examined. Thermal fluxes are assessed for two different indoor temperature settings, while the operation of the heating unit is assumed to be continuous. The transient thermal analysis with its mathematical formulation and solution are based on the thermal-network modelling approach, while the solar heat gain through glazing relies on the sunlit-pattern approach; in this way, the stricken by the solar rays glazing area is projected onto any interior surfaces to form the so called “sunlit” areas. As the orientation, glazing proportion and aspect ratio of the building zone vary, so do the sizes and shapes of the illuminated “sunlit” areas. Accordingly, the delivered into the zone direct solar energy and its diffused and ground reflected components can be determined. The adopted methodology provides a more accurate determination of solar heat gain with respect to glazing proportion and orientation as well as zone aspect ratio. With regard to surface orientation, glazing proportion and aspect ratio, computer results demonstrate the improvement of the thermal performance for a building zone with a south oriented glazing surface, as well as the deterioration for the other surface orientations; relative increases/decreases in the energy fluxes of a rectangular shaped building zone compared to a square-shaped building zone can reach up to 50%/100%.



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Geochemical fractionation and pollution assessment of Zn, Cu, and Fe in surface sediments from Shadegan Wildlife Refuge, southwest of Iran

Abstract

This research focuses on the fractionation and distribution patterns of heavy metals (Zn, Cu, and Fe) in surficial sediments collected from Shadegan Wildlife Refuge, the biggest wetland in southern part of Iran, to provide an overall classification for the sources of metals in the study area using a sequential extraction method. For this purpose, a four-step sequential extraction technique was applied to define the partitioning of the metals into different geochemical phases of the sediment. The results illustrated that the average total level of Zn, Cu, and Fe in surface sediments were 55.20 ± 16.04, 22.86 ± 5.68, and 25,979.01 ± 6917.91 μg/g dw, respectively. On the average, the chemical partitioning of all metals in most stations was in the order of residual >oxidizable-organic > acid-reducible > exchangeable. In the same way, the results of calculated geochemical indices revealed that Cu, Zn, and Fe concentrations are mainly influenced by lithogenic origins. Compared with consensus-based SQGs, Cu was likely to result in occasionally harmful biological effects on the biota.



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Pb-induced changes in roots of two cultivated rice cultivars grown in lead-contaminated soil mediated by smoke

Abstract

Nowadays, public concerns regarding deleterious effect of lead (Pb) is on rise due to its abundance and toxic effect on plants and other living organisms. In plants, it has no noticeable biological importance but can cause various morphological, physiological, and biochemical malfunctions. To evaluate the remediating potential of plant-derived smoke (Cymbopogon jwarancusa), a pot culture experiment was designed to investigate the physiological, biochemical, metabolic, and antioxidant parameters of roots in lead (0 (control), 500, 1000, and 1500 ppm)-contaminated soil. Under dark condition, seeds were primed in smoke solution with two dilutions (1:500 and 1:1000) for 24 h. With an increasing concentration of Pb stress, fresh and dry weight and total nitrogen and protein contents decreased significantly while an increase was observed in smoke-treated seed. With increasing Pb stress level, metabolites (i.e., proline, total soluble sugar, total soluble protein, glycine betaine), and antioxidants (i.e., superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, malonyldialdehyde, and H2O2), contents of roots were increased in non-treated (without smoke treatment) samples, whereas comparatively, a low level of alteration in aforementioned metabolites and antioxidative parameters was observed in the seeds treated with smoke solution. These results suggest a positive role of smoke in alleviating lead-induced changes in roots of two cultivated cultivars of rice grown in Pb-contaminated soil.



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Short-duration hydrothermal fermentation of food waste: preparation of soil conditioner for amending organic-matter-impoverished arable soils

Abstract

Soil conditioners can be used to compensate for the insufficient soil nutrition and organic matter (OM) of arable soils. However, the traditional preparation method for soil conditioners is lengthy and requires facilities that occupy large tracts of land. In this study, a short-duration hydrothermal fermentation (SHF) method was developed for the preparation of soil conditioners from food waste. The SHF method required only 18 h to produce soil conditioners with physicochemical characteristics that were similar to those of soil conditioners obtained through traditional fermentation (TF), which takes 20 days to complete. Inoculation and dynamic SHF significantly affected the distribution of different molecular weight fractions in the prepared soil conditioners. The results of spectral analysis revealed that a large amount of soluble microbial byproducts and carbohydrate C formed in the SHF soil conditioner. This effect indicated that the SHF soil conditioner supplied not only immediately available nutrients, which can stimulate the growth of soil microbial communities, but also provided sustained-release nutrients for the long-term cultivation of crops on OM-impoverished soils. Cyanobacteria were present in the SHF soil conditioner at a relative abundance of 6.29%, which was 28.6 and 314.5 times those in the raw material and TF soil conditioner, respectively. Amending OM-impoverished soil with the SHF soil conditioner enhanced the carbon pool management index of the resulting SHF soil by 1.50 and 1.12 times those of unfertilized soil and TF soil, respectively. These results indicated that the SHF soil exhibited a high capacity to supply nutrients for crop growth.



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Influence of pH, EDTA/Fe(II) ratio, and microbial culture on Fe(II)-mediated autotrophic denitrification

Abstract

Fe(II)-mediated autotrophic denitrification with four different microbial cultures under different pH and EDTA/Fe(II) conditions was investigated in batch bioassays. Initially, the highest nitrate removal (72%) was achieved with an activated sludge inoculum. The use of pure cultures of Pseudogulbenkiania strain 2002 and Thiobacillus denitrificans resulted in a 55 and 52% nitrate removal, respectively. No denitrification was observed for a mixed culture dominated by Thiobacillus thioparus and T. denitrificans. A longer enrichment on Fe(II) and the supplementation of thiosulfate as additional electron donor were needed to stimulate the denitrifying activity of the Thiobacillus-mixed culture. A second subculture on Fe(II) as sole electron donor resulted in higher denitrification efficiencies for all microbial cultures. In particular, nitrate removal reached up to 84% with a specific nitrate removal rate of 1.160 mM·(g VSS·day)−1 in the bioassays seeded with the Thiobacillus-mixed culture. All cultures were favored by decreasing the EDTA/Fe(II) molar ratio from 2.0 to 0.5. The most significant denitrification enhancement was observed for the Pseudogulbenkiania species, indicating a lower tolerance to EDTA. The two pure cultures effectively maintained denitrification at pH 7.0 and were more sensitive to a pH decrease. Conversely, the optimal pH was 6.0 for the Thiobacillus-mixed and activated sludge cultures.



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Microvascular ultrastructural changes precede cognitive impairment in the murine APPswe/PS1dE9 model of Alzheimer’s disease

Abstract

Cerebral and systemic organ microvascular pathologies coexist with human Alzheimer’s disease (AD) neuropathology. In this study, we hypothesised that both cerebral and systemic microvascular pathologies exist in 4- to 5-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice prior to the onset of cognitive impairment. To assess this we examined recognition memory in both wild-type and APP/PS1 mice using the object recognition task (ORT; n = 11 per group) and counted thioflavin-S-positive plaques in brain (n = 6 per group). Vascular casts of brain, liver, spleen and kidneys were examined using scanning electron microscopy (n = 6 per group), and the urinary albumin-to-creatinine ratio (uACR; n = 5 per group) was measured as an index of glomerular permeability. Murine recognition memory was intact, as demonstrated by a significant preference for the novel object in the ORT paradigm. Brain sections of wild-type mice were devoid of thioflavin-S positivity, whereas age-matched APP/PS1 mice had an average of 0.88 ± 0.22 thioflavin-S-positive plaques in the cortex, 0.42 ± 0.17 plaques in the dentate gyrus and 0.30 ± 0.07 plaques in the cornus ammonis 1 region. The profiles of casted cerebral capillaries of wild-type mice were smooth and regular in contrast to those of APP/PS1 mice which demonstrate characteristic (0.5–4.6 μm) ‘tags’. APP/PS1 mice also had a significantly reduced hepatic vessel number (p = 0.0002) and an increase in the number of splenic microvascular pillars (p = 0.0231), in the absence of changes in either splenic microvascular density (p = 0.3746) or glomerular ultrastructure. The highly significant reduction in uACR in APP/PS1 mice compared to wild-type (p = 0.0079) is consistent with glomerular microvascular dysfunction. These findings highlight early microvascular pathologies in 4- to 5-month-old APP/PS1 transgenic mice and may indicate an amenable target for pharmacological intervention in AD.



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Loss of NHEJ1 Protein Due to a Novel Splice Site Mutation in a Family Presenting with Combined Immunodeficiency, Microcephaly, and Growth Retardation and Literature Review

Abstract

Introduction

Non-homologous end joining gene 1 (NHEJ1) defect is a rare form of primary immune deficiency. Very few cases have been described from around the world.

Purpose

We are reporting the first family from the Arabian Gulf with three siblings presenting with combined immunodeficiency (CID), microcephaly, and growth retardation due to a novel NHEJ1 splice site mutation, in addition to a review of the previously published literature on this subject.

Methods

Patients’ clinical, immunological, and laboratory features were examined. Samples were subjected to targeted next-generation sequencing (NGS). The pathogenic change in NHEJ1 was confirmed by Sanger sequencing, then further assessed at the RNA and protein levels.

Results

Patients were found to have a homozygous splice site mutation immediately downstream of exon 3 in NHEJ1 (c.390 + 1G > C). This led to two distinct mRNA products, one of which demonstrated skipping of the last 69 basepairs (bp) of exon 3 while the other showed complete skipping of the entire exon. Although both deletions were in-frame, immunoblotting did not reveal any NHEJ1 protein products in patient cells, indicating a null phenotype.

Conclusion

Patients presenting with CID, microcephaly, and growth retardation should be screened for NHEJ1 gene mutations. We discuss our data in the context of one of our patients who is still alive at the age of 30 years, without transplantation, and who is the longest known survivor of this disease.



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Use of a Polyethylene Bag to Reduce Perioperative Regional and Whole-Body Heat Losses in Low-Birth-Weight Neonates

In the delivery room, wrapping a low-birth-weight neonate (defined as ≤2.499 g) in a polyethylene bag reduces the risk of hypothermia. However, extended use of the bag (e.g., during neonatal surgery) might conceivably increase the risk of thermal stress and thus body overheating. Here, we assessed the efficacy of a polyethylene bag in infants assigned to wrap (W) or nonwrap (NW, control) groups during placement of a percutaneous vena cava catheter by applying a new mathematical model that calculates heat exchanges for covered and uncovered body segments. At the end of the placement procedure, the W and NW groups did not differ significantly in terms of whole-body heat loss (15.80 versus 14.97 kJ·h−1·kg−1, resp.), whereas the abdominal skin temperature was slightly but significantly higher (by 0.32°C) in the W group. Greater evaporation in the W group (2.49 kJ·h−1·kg−1) was primarily balanced by greater whole-body radiant heat loss (3.44 kJ·h−1·kg−1). Wrapping the neonate in a polyethylene bag provides a small thermal benefit when catheter placement takes a long time. Given that polyethylene is transparent to radiant energy, it might be of value to incorporate polymers that are less transparent at infrared wavelengths.

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Synthesis and Anticancer Activities of 4-[(Halophenyl)diazenyl]phenol and 4-[(Halophenyl)diazenyl]phenyl Aspirinate Derivatives against Nasopharyngeal Cancer Cell Lines

Aspirin and azo derivatives have been widely studied and have drawn considerable attention due to diverse biological activities. In this study, a series of 4-[(halophenyl)diazenyl]phenyl aspirinate derivatives were synthesized from the reaction of aspirin with 4-[(halophenyl)diazenyl]phenol via esterification, in the presence of DCC/DMAP in DCM with overall yield of 45–54%. 4-[(Halophenyl)diazenyl]phenol was prepared prior to esterification from coupling reaction of aniline derivatives and phenol in basic solution. All compounds were characterized using elemental analysis, FTIR, and 1H and 13C NMR spectroscopies. All compounds were screened for their anticancer activities against nasopharyngeal cancer (NPC) HK-1 cell lines and the viability of cultured cells was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]-based colorimetric assay. 4-[(E)-(Fluorophenyl)diazenyl]phenol showed the highest anticancer activity against NPC HK-1 cell lines compared to other synthesized compounds. 4-[(Halophenyl)diazenyl]phenyl aspirinate showed low cytotoxicity against NPC HK-1 cell lines compared to 4-[(halophenyl)diazenyl]phenol but better anticancer activity than aspirin alone.

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Prototype Generation Using Self-Organizing Maps for Informativeness-Based Classifier

The nearest neighbor is one of the most important and simple procedures for data classification task. The , as it is called, requires only two parameters: the number of and a similarity measure. However, the algorithm has some weaknesses that make it impossible to be used in real problems. Since the algorithm has no model, an exhaustive comparison of the object in classification analysis and all training dataset is necessary. Another weakness is the optimal choice of parameter when the object analyzed is in an overlap region. To mitigate theses negative aspects, in this work, a hybrid algorithm is proposed which uses the Self-Organizing Maps (SOM) artificial neural network and a classifier that uses similarity measure based on information. Since SOM has the properties of vector quantization, it is used as a Prototype Generation approach to select a reduced training dataset for the classification approach based on the nearest neighbor rule with informativeness measure, named NN. The SOMNN combination was exhaustively experimented and the results show that the proposed approach presents important accuracy in databases where the border region does not have the object classes well defined.

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Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.

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The Bacteriological Quality, Safety, and Antibiogram of Salmonella Isolates from Fresh Meat in Retail Shops of Bahir Dar City, Ethiopia

The habit of raw meat consumption in addition to the poor hygienic standards and lack of knowledge contribute to food-borne diseases outbreaks. The objective of this research was to assess the bacterial quality and safety of fresh meat from retail Bahir Dar City, Ethiopia. A total of 30 fresh meat samples were collected from butcher shops. Standard bacteriological methods were used to isolate and enumerate bacteria. Kirby-Bauer disk diffusion method was used for antimicrobial susceptibility testing of Salmonella isolates. The mean counts of AMB, TC, and S. aureus were log104.53, 3.97, and 3.88 log10cfu/g, respectively. Salmonella was isolated from 21 (70%) of the samples. Salmonella isolates in this study were highly susceptible to ciprofloxacin, gentamycin, and norfloxacin while they were resistant to erythromycin and tetracycline. High rate of multiple drug resistance was also noticed in Salmonella isolates. The microbial loads of meat were above the recommended microbial safety limits. Besides this, the isolation rate of Salmonella was high and high levels of drug resistance were documented for Salmonella isolates. Measures on handling and appropriate personal hygiene practices of workers in the retail shops are recommended to reduce the change of forborne disease outbreaks.

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Interaction of Solid Lipid Nanoparticles and Specific Proteins of the Corona Studied by Surface Plasmon Resonance

The applications of pharmaceutical and medical nanosystems are among the most intensively investigated fields in nanotechnology. A relevant point to be considered in the design and development of nanovehicles intended for medical use is the formation of the “protein corona” around the nanoparticle, that is, a complex biomolecular layer formed when the nanovehicle is exposed to biological fluids. The chemical nature of the protein corona determines the biological identity of the nanoparticle and influences, among others, the recognition of the nanocarrier by the mononuclear phagocytic system and, thus, its clearance from the blood. Recent works suggest that Surface Plasmon Resonance (SPR), extensively employed for the analysis of biomolecular interactions, can shed light on the formation of the protein corona and its interaction with the surroundings. The synthesis and characterization of solid lipid nanoparticles (SLN) coated with polymers of different chemical nature (e.g., polyvinyl alcohol, chitosans) are reported. The proof-of-concept for the use of SPR technique in characterizing protein-nanoparticle interactions of surface-immobilized proteins (immunoglobulin G and bovine serum albumin, both involved in the formation of the corona) subjected to flowing SLN is demonstrated for non-chitosan-coated nanoparticles. All assayed nanosystems show more preference for IgG than for BSA, such preference being more pronounced in the case of polyvinyl-alcohol-coated SLN.

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An Improvement for Fuzzy Stochastic Goal Programming Problems

We examined the solution process for linear programming problems under a fuzzy and random environment to transform fuzzy stochastic goal programming problems into standard linear programming problems. A previous paper that revised the solution process with the lower-side attainment index motivated our work. In this paper, we worked on a revision for both-side attainment index to amend its definition and theorems. Two previous examples were used to examine and demonstrate our improvement over previous results. Our findings not only improve the previous paper with both-side attainment index, but also provide a theoretical extension from lower-side attainment index to the both-side attainment index.

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NSiteMatch: Prediction of Binding Sites of Nucleotides by Identifying the Structure Similarity of Local Surface Patches

Nucleotides play a central role in life-form metabolism, by interacting with proteins and mediating the function of proteins. It is estimated that nucleotides constitute about 15% of the biologically relevant ligands included in PDB. Prediction of binding sites of nucleotides is useful in understanding the function of proteins and can facilitate the in silico design of drugs. In this study, we propose a nucleotide-binding site predictor, namely, NSiteMatch. The NSiteMatch algorithm integrates three different strategies: geometrical analysis, energy calculation, and template comparison. Unlike a traditional template-based predictor, which identifies global similarity between target structure and template, NSiteMatch concerns the local similarity between a surface patch of the target protein and the binding sites of template. To this end, NSiteMatch identifies more templates than traditional template-based predictors. The NSiteMatch predictor is compared with three representative methods, Findsite, Q-SiteFinder, and MetaPocket. An extensive evaluation demonstrates that NSiteMatch achieves higher success rates than Findsite, Q-SiteFinder, and MetaPocket, in prediction of binding sites of ATP, ADP, and AMP.

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Nuclear Waste Management Decision-Making Support with MCDA

The paper proposes a multicriteria decision analysis (MCDA) framework for a comparative evaluation of nuclear waste management strategies taking into account different local perspectives (expert and stakeholder opinions). Of note, a novel approach is taken using a multiple-criteria formulation that is methodologically adapted to tackle various conflicting criteria and a large number of expert/stakeholder groups involved in the decision-making process. The purpose is to develop a framework and to show its application to qualitative comparison and ranking of options in a hypothetical case of three waste management alternatives: interim storage at and/or away from the reactor site for the next 100 years, interim decay storage followed in midterm by disposal in a national repository, and disposal in a multinational repository. Additionally, major aspects of a decision-making aid are identified and discussed in separate paper sections dedicated to application context, decision supporting process, in particular problem structuring, objective hierarchy, performance evaluation modeling, sensitivity/robustness analyses, and interpretation of results (practical impact). The aim of the paper is to demonstrate the application of the MCDA framework developed to a generic hypothetical case and indicate how MCDA could support a decision on nuclear waste management policies in a “small” newcomer country embarking on nuclear technology in the future.

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From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.

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Spreadability of Ag Layer on Oxides and High Performance of AZO/Ag/AZO Sandwiched Transparent Conductive Film

Single layers of indium tin oxide (ITO), aluminum-doped zinc oxide (AZO), and Ag, bilayers of ITO/Ag and AZO/Ag, and sandwiched layers of ITO/Ag/ITO (IAI) and AZO/Ag/AZO (ZAZ) were fabricated on ordinary glass substrates using magnetron sputtering. The surface morphologies of single layers and bilayers were measured. The sheet resistance and transmittance of the sandwiched layers were investigated. The results showed that the spreadability of the Ag on the AZO was significantly better than that on the ITO or bare glass substrate. The spreadability of Ag on underlayers influences obviously the performance of transparent conductive oxide/Ag/transparent conductive oxides (TCO/Ag/TCO or TAT). The sheet resistance and transmittance of the ZAZ sandwiched layer with the matching of 35 nm AZO (35 nm)/Ag (9 nm)/AZO (35 nm) fabricated in this paper were low to 3.84 Ω/sq and up to 85.55% at 550 nm, respectively. Its maximum Haacke figure of merit was 0.05469 Ω−1, higher than that of IAI multilayer.

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Resource Allocation in Heterogeneous Buffered Cognitive Radio Networks

Resources available for operation in cognitive radio networks (CRN) are generally limited, making it imperative for efficient resource allocation (RA) models to be designed for them. However, in most RA designs, a significant limiting factor to the RA’s productivity has hitherto been mostly ignored, the fact that different users or user categories do have different delay tolerance profiles. To address this, in this paper, an appropriate RA model for heterogeneous CRN with delay considerations is developed and analysed. In the model, the demands of users are first categorised and then, based on the distances of users from the controlling secondary user base station and with the assumption that the users are mobile, the user demands are placed in different queues having different service capacities and the resulting network is analysed using queueing theory. Furthermore, to achieve optimality in the RA process, an important concept is introduced whereby some demands from one queue are moved to another queue where they have a better chance of enhanced service, thereby giving rise to the possibility of an improvement in the overall performance of the network. The performance results obtained from the analysis, particularly the blocking probability and network throughput, show that the queueing model incorporated into the RA process can help in achieving optimality for the heterogeneous CRN with buffered data.

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Spinal Cord Injury due to Tumour or Metastasis in Aragón, Northeastern Spain (1991–2008): Incidence, Time Trends, and Neurological Function

Purpose. Understanding the presentation of spinal cord injury (SCI) due to tumours considering population distribution and temporal trends is key to managing SCI health services. This study quantified incidence rates, function scores, and trends of SCI due to tumour or metastasis over an 18-year time period in a defined region in Spain. Methods. A retrospective cohort study included in-and outpatients with nontraumatic SCI due to tumour or metastasis admitted to a metropolitan hospital in Spain between 1991 and 2008. Main outcome measures were crude and age- and sex-adjusted incidence rates, tumour location and type, distribution by spinal level, neurological level of injury, and impairment ASIA scores. Results. Primary tumour or metastasis accounted for 32.5% of nontraumatic SCI with an incidence rate of 4.1 per million population. Increasing rates with age and over time were observed. Major pathology groups were intradural-extramedullary masses from which meningiomas and neurinomas accounted for 40%. Lesions were mostly incomplete with predominant ASIA Grade D. Conclusions. Increasing incidence rates of tumour-related SCI over time in the middle-aged and the elderly suggest a growing need for neurooncology health resources in the future.

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Evaluation of transient-evoked otoacoustic emissions in a healthy 1–10 year pediatric cohort in Sub-Saharan Africa

Transient-evoked otoacoustic emissions (TEOAEs) monitor cochlear function. High pass rates have been reported for industrialized countries. Pass rates in low and middle income countries such as Sub-Saharan Africa are rare, essentially lower and available for children up to 4 years of age and frequently based on hospital recruitments.This study aims at providing additional TEOAE pass rates of a healthy Sub-Saharan cohort aged 1–10 years with data from Gabon, Ghana and Kenya. Potentially confounding factors (recruitment site, age) are taken into consideration.

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More on molar incisor hypomineralisation (MIH) and linear enamel hypoplasia (LEH) in archaeological human remains



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Mesh Sling For Stress Urinary Incontinence Surgery

Mesh Sling For Stress Urinary Incontinence Surgery
PreOp® Patient Education - https://PreOp.com
StoreMD™ - https://store.preop.com

Patient Education & Patient Engagement

What is Mesh Sling For Stress Urinary Incontinence Surgery?

SUI is a problem when the pelvic muscles that support the bladder and urethra, or the urethral sphincter are weak. Support problems can start from pressure on these muscles with pregnancy and childbirth, chronic constipation, extra body weight, smoking, coughing and certain activities like heavy lifting that are repeated often.

Your doctor has recommended a mesh sling to treat your stress urinary incontinence. Before we talk about this surgical option, let’s review some information about the female body and this medical condition.

The female bladder is behind the pubic bone and on top of the vagina. It is in the pelvis, the lowest part of the body between the hips.

The bladder muscle squeezes to empty urine through a short tube called the urethra. This tube lies under the pubic bone and in front of the vagina.

The urethral sphincter is a muscle at the opening to the bladder. You control urination by relaxing and squeezing this muscle.
Stress urinary incontinence, SUI (say S-U-I) is uncontrolled urine leaking from pressure on the bladder and urethra. This pressure happens with sneezing, coughing, laughing and exercise.

SUI is a problem when the pelvic muscles that support the bladder and urethra, or the urethral sphincter are weak.
Support problems can start from pressure on these muscles with pregnancy and childbirth, chronic constipation, extra body weight, smoking, coughing and certain activities like heavy lifting that are repeated often.

Other risks for female SUI include low estrogen and menopause
genetics, meaning a woman can be born at risk for weak tissue
and it can be an occasional side effect of pelvic surgery
Some changes can make leaking better without surgery, drink smaller amounts at a time, quit smoking if you smoke and work to get to a healthy weight if you are overweight. - more:

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Patient Education & Patient Engagement



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(pembrolizumab) Monotherapy in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous ... - Business Wire (press release)

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“We are encouraged by the positive impact that KEYTRUDA has had on many cancer patients, including those with previously treated recurrent or metastatic head and neck cancer, and we remain confident that KEYTRUDA is an important therapy for this ...

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Chemotherapeutic inhibits glioblastoma growth and radiation resistance

Glioblastoma is a primary brain tumour with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumour cells - glioma stem cells - is responsible for glioblastoma's tumourigenesis, treatment...

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MicroRNA-181a and its target Smad 7 as potential biomarkers for tracking child acute lymphoblastic leukemia

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Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Marwa Nabhan, Manal L. Louka, Eman Khairy, Fathy Tash, Randa Ali-Labib, Safinaz El-Habashy
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic tumor. MiR-181a was expected to have a role in the development of hematological malignancies; it might act as tumor suppressor or oncogene. Smad7 was selected as miR-181a target pair. It is a negative regulator for the TGF-β1 signaling pathway. In this study, relative expression levels of miR-181a by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), both Smad 7 and TGF-β1 proteins levels by enzyme linked immunosorbent assay (ELISA) were all measured in serum of 60 child, 30 with ALL and 30 age and sex matched healthy child as control group. MiR-181a expression showed highly significant decrease; plus a significant increase and decrease of Smad7 and TGF-β1 protein levels respectively, in serum samples of ALL as compared to control group. MiR-181a expression achieved a highly significant positive and a significant negative correlation with TGF-β1 and Smad7 respectively. Furthermore, the levels of Smad7 and TGF-β1 were negatively correlated with each other (p<0.05). Although, positivity rate of both Smad7 and TGF-β1 in ALL group increased with presence of hepatosplenomegaly, still there was no statistical significance. In conclusion, miR-181a could act as a tumor suppressor in pediatric ALL with over expression of its target pair, Smad7. Smad7 regulates TGF-β1 signaling via a negative feedback loop and mediates the interaction between TGF-β1 and other signaling pathways; suggesting that Smad7 over expression may have therapeutic potential in ALL.



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Glutathione S-transferase (GSTM1, GSTT1) polymorphisms and JOAG susceptibility: A case control study and meta-analysis in glaucoma

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Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Manzoor Ahmad Malik, Viney Gupta, Swati Shukla, Jasbir Kaur
PurposeGlutathione S transferase (GST) polymorphisms have been considered risk factors for the development of glaucoma. The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with juvenile open-angle glaucoma (JOAG) in Indian patients.MethodsA case-control study was performed to investigate the associations of GSTM1 and GSTT1 in juvenile open-angle glaucoma. The genotype of GSTM1 and GSTT1 were determined in 73 juvenile open-angle glaucoma patients, and 70 controls matched by age and sex by polymerase chain reaction method. We also performed a meta-analysis of sixteen published studies on GSTM1 and GSTT1 and evaluated the association between the GSTM1 and GSTT1 polymorphisms and glaucoma (JOAG & POAG).Published literature from PubMed and other databases were retrieved. All studies evaluating the association between GSTM1 and GSTT1 polymorphisms and glaucoma (JOAG & POAG) risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.ResultsIn the present study, we observed there is no association of GSTM1 (OR=0.680; 95% CI=0.323–1.433; p=0.311) or GSTT1 (OR=0.698; 95% CI=0.307–1.586; p=0.391) with JOAG. In the present meta-analysis, significantly increased glaucoma (JOAG & POAG) risk was found among subjects carrying GSTM1 null genotype (OR=1.177; 95% CI=1.028–1.348; p=0.018) but not among subjects carrying GSTT1 deletion genotype (OR=1.186; 95% CI=0.992–1.417; p=0.061).ConclusionsThe present case-control study found that GSTM1 and GSTT1 polymorphism are not associated with JOAG risk in North Indian population. The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with glaucoma (JOAG & POAG) risk. To the best of our knowledge, this is the first study in the world to investigate role of GSTM1 and GSTT1 polymorphisms with JOAG susceptibility. Given the limited sample size, the associations between GST polymorphism and glaucoma risk needs further investigation.



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Epigenetic silencing of miRNA-143 regulates apoptosis by targeting BCL2 in human intervertebral disc degeneration

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Kangcheng Zhao, Yukun Zhang, Liang Kang, Yu Song, Kun Wang, Shuai Li, Xinghuo Wu, Wenbin Hua, Zengwu Shao, Shuhua Yang, Cao Yang
Accumulating evidence indicates that microRNAs can regulate the apoptosis of various cells. Apoptosis of nucleus pulposus cells plays an important role in the progression of intervertebral disc degeneration. The aim of this study is to investigate whether microRNA-143 (miRNA-143) is involved in the progression of intervertebral disc degeneration. In this study, the expression of miRNA-143 and its biological modulatory effects were examined. Messenger RNA and protein expression of miRNA-143 and B-cell lymphoma-2 (BCL2) in both normal and degenerative disc tissues was determined by using RT-PCR and western-blot assays. After miRNA-143 transfection, BCL2 expression and NP cell apoptosis were assessed by using RT-PCR, western-blot, and flow cytometry. The relationship between miRNA-143 and BCL2 was assessed by bioinformatics and dual luciferase assays. Epigenetic regulation of miRNA-143 was determined by methylation-specific PCR and the effect of hypomethylation using 5-AZA. In this study, miRNA-143 expression significantly increased, while that of BCL2 decreased in degenerative disc specimens. In addition, CpG islands in the promoter region of miRNA-143 were hypomethylated in degenerative disc tissues. Furthermore, bioinformatics analysis and luciferase reporter assay indicated that BCL2 was a target gene of miRNA-143, and miRNA-143 suppressed BCL2 messenger RNA (mRNA) and protein expression. MiRNAmiRNA-143 overexpression enhances apoptosis of nucleus pulposus cells, while miRNA-143 inhibitor had the opposite effect. BCL2 knockdown reversed the effects of the miRNA-143 inhibitor on nucleus pulposus apoptosis. Our results suggest that miRNA-143 promotes the progression of nucleus pulposus apoptosis by directly targeting BCL2, providing a potential therapeutic target for the treatment of intervertebral disc degeneration disease.

Graphical abstract

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