Δευτέρα, 3 Απριλίου 2017

Paura ossessiva di dormire e di morire, dovuta a reali problemi di salute - Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog)


Paura ossessiva di dormire e di morire, dovuta a reali problemi di salute
Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog)
In più si è aggiunto due settimane fa un gonfiore improvviso mentre mangiavo ai linfonodi del collo; i miei si sono preoccupati e mi hanno portata in pronto soccorso: da quel giorno, oltre ad avere rilevato analisi del sangue preoccupanti, ho sempre ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2owu9Mj
via IFTTT

On this day: April 4 - LocalNews8.com


LocalNews8.com

On this day: April 4
LocalNews8.com
2013: Movie critic Roger Ebert, the first film critic to win the Pulitzer Prize for Criticism, dies at the age of 70 in Chicago, Illinois, after a recurrence of cancer. Ebert, who had lived with cancer of the thyroid and salivary glands since 2002, was ...

and more »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nWqh5B
via IFTTT

Free Triiodothyronine/Free Thyroxine Ratio rather than Thyrotropin is more associated with Metabolic Parameters in Healthy Euthyroid Adult Subjects

Abstract

Objective

The interrelation between TSH, thyroid hormones, and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome.

Design

This is a cross-sectional study that included subjects in a medical health check-up program at a single institution.

Patients

The study included 132,346 participants (66,991 men and 65,355 women) aged over 18 years who had TSH, free T4 (FT4), and free T3 (FT3) levels within the institutional reference ranges.

Measurements

TSH, FT4, FT3, and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin, and glucose were measured.

Results

There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status, and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women.

Conclusions

TSH levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH.

This article is protected by copyright. All rights reserved.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2owNmNl
via IFTTT

Safety and Efficacy of Treatment with Asfotase Alfa in Patients with Hypophosphatasia: Results from a Japanese Clinical Trial

Summary

Objective

Hypophosphatasia (HPP) is a rare skeletal disease characterized by hypomineralization and low alkaline phosphatase activity. Asfotase alfa (AA) has been recently developed to treat HPP complications. This study evaluated its safety and efficacy in Japan.

Design

Open-label, multicenter, prospective trial. Patients were enrolled in 11 hospitals from June 2014 to July 2015.

Patients

Thirteen patients (9 females, 4 males) ages 0 days to 34 years at baseline were enrolled and treated with AA (2 mg/kg three times weekly subcutaneously in all but one patient). All had ALPL gene mutations. HPP forms were perinatal (n = 6), infantile (n = 5), childhood (n = 1), and adult (n = 1).

Measurements

Safety determined from adverse events (AEs) and laboratory data was the primary outcome measure. Efficacy was assessed as a secondary outcome measure from overall survival, respiratory status, rickets severity, and gross motor development.

Results

Injection site reactions were the most frequent AEs. Serious AEs possibly related to treatment were convulsion and hypocalcemia observed in a patient with the perinatal form. In addition, hypercalcemia and/or hyperphosphatemia was observed in three patients with the infantile form and a low-calcium and/or low-phosphate formula was given to these patients. With respect to efficacy, all patients survived and the radiographic findings, developmental milestones, and respiratory function improved.

Conclusion

AA therapy improved skeletal, respiratory, and physical symptoms with a few serious AEs in patients with HPP. Our results add support to the safety and efficacy of AA therapy for HPP patients.

This article is protected by copyright. All rights reserved.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyvY6l
via IFTTT

Distal appendicular skeletal involvement of diffuse large B-cell lymphoma on technetium-99m methylenediphosphonate bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: a case report

We report a case of a patient with appendicular bone involvement of diffuse large B-cell lymphoma visualized by whole-body technetium-99m methylenediphosphonate bone scintigraphy (bone scan) and 18F-fluorodeoxygl...

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyCMkd
via IFTTT

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

Transforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remain...

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRYB09
via IFTTT

The germline variants in DNA repair genes in pediatric medulloblastoma: a challenge for current therapeutic strategies

The defects in DNA repair genes are potentially linked to development and response to therapy in medulloblastoma. Therefore the purpose of this study was to establish the spectrum and frequency of germline varian...

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2owmUng
via IFTTT

On this day: April 4 - KESQ


KESQ

On this day: April 4
KESQ
2013: Movie critic Roger Ebert, the first film critic to win the Pulitzer Prize for Criticism, dies at the age of 70 in Chicago, Illinois, after a recurrence of cancer. Ebert, who had lived with cancer of the thyroid and salivary glands since 2002, was ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyJmHn
via IFTTT

Thyroid Cancer Market Pipeline Review – Competitor Information, Analysis, and Insights to Formulate Effective R&D ... - Medgadget (blog)


Thyroid Cancer Market Pipeline Review – Competitor Information, Analysis, and Insights to Formulate Effective R&D ...
Medgadget (blog)
Detailed analysis of the “Thyroid Cancer-Pipeline Review, H1 2017” helps to understand the various types of Continuous Positive Airway Pressure (CPAP) Machine products that are currently in use, along with the variants that would gain prominence in the ...
Latest report on thyroid cancer pipeline, therapeutics assessment and drug profiles H1 2017 just publishedWhaTech

all 8 news articles »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVQ9yi
via IFTTT

Interpace Diagnostics (IDXG) Reports European Patent Approval for Technology Underlying ThyraMIR® microRNA ... - StreetInsider.com


Interpace Diagnostics (IDXG) Reports European Patent Approval for Technology Underlying ThyraMIR® microRNA ...
StreetInsider.com
The Company currently has three commercialized molecular tests: PancraGEN®, for the evaluation of pancreatic cysts and assessment of risk of concomitant or subsequent cancer; ThyGenX®, for the diagnosis of thyroid cancer from thyroid nodules utilizing ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oTkUls
via IFTTT

Are your dentures irritating you? If ill-fitting, they can cause cancer - Hindustan Times


Hindustan Times

Are your dentures irritating you? If ill-fitting, they can cause cancer
Hindustan Times
“Chronic mucosal irritation resulting from ill-fitting dentures may be considered a risk factor for the development of oral cancer, such cancers occur commonly over the lateral border of the tongue,” said the research conducted by Hitesh Rajendra ...
Oral Cancer Awareness Month: Irritation From Ill-Fitting Dentures May Lead to CancerNDTV

all 3 news articles »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVR5mp
via IFTTT

Evolution and diversity of ram-suction feeding in damselfishes (Pomacentridae)

Abstract

The cerato-mandibular (c-md) ligament is a synapomorphy within Pomacentridae that creates a tight link between the lower jaws and the hyoid bars. However, this morphological trait has been secondarily lost in multiple lineages during evolution. A previous study revealed that the loss of this trait acted as a release of evolutionary constraints, leading to a cascade of morphological changes such elongated buccal jaws and a slender body. Ecomorphological interpretations suggested the loss of the c-md ligament has ultimately led to a new adaptive peak in zooplanktivory through an optimization of the ram feeding mode associated with a specialization in pelagic feeding. Here, we tested these hypotheses by comparing functional and diet diversity between damselfish species with and without the c-md ligament. Although species lacking the c-md ligament presented a conserved kinematic pattern resulting from high ram and low suction performances, our results did not support an optimization of the ram feeding mode. Indeed, some species with the c-md ligament showed the same or exceeded the ram performance of species without the c-md ligament. The species with the c-md ligament had a more diverse kinematic pattern exploring the entire ram-suction functional range in damselfishes. Finally, our results did not show any diet variations associated with the loss of the c-md ligament. Our study furthers the understanding of how a morphological trait has shaped, by its presence or absence, the ecomorpho-functional diversification of Pomacentridae.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nDQS4T
via IFTTT

Baby joy for Dundee cancer survivor Kirsten - Evening Telegraph


Evening Telegraph

Baby joy for Dundee cancer survivor Kirsten
Evening Telegraph
The Dundee City Council social worker first believed she was suffering from a common cold before initially being diagnosed with tonsillitis. She had previously said she had discovered rock hard lumps the size of peas on the left-hand side of her neck ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRyx53
via IFTTT

Orange Regional offers free cancer screenings - The Chronicle


Orange Regional offers free cancer screenings
The Chronicle
MIDDLETOWN — Orange Regional Medical Center will offer the community free oral, head and neck cancer screenings in conjunction with Oral, Head and Neck Cancer Awareness week, April 2-9. Appointments are available on April 3, April 4 and April 7 at ...

and more »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nDPUFA
via IFTTT

The Immunoregulatory Roles of Antibody Glycosylation

Publication date: Available online 3 April 2017
Source:Trends in Immunology
Author(s): Madeleine F. Jennewein, Galit Alter
Beyond their role in neutralization, antibodies mediate functions such as phagocytosis, cytotoxicity, and maintenance of immune homeostasis. Two modifications to the constant domain control antibody activity: theirreversible genomic selection of isotype/subclass and alterations in glycosylation. Because glycosylation alters the affinity of antibodies for Fc receptors, evidence suggests that glycosylation is a central mechanism for the immune system to tune a broad range of biological activities. While monoclonal therapeutics have exploited glycosylation to improve function, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors isunknown. Here, we review the process of antibody glycosylation, how it changes with disease, how it impacts antibody functionality, and the potential for deliberately controlling this biological activity.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVGEiU
via IFTTT

Orange Regional offers free cancer screenings - The Photo News


Orange Regional offers free cancer screenings
The Photo News
MIDDLETOWN — Orange Regional Medical Center will offer the community free oral, head and neck cancer screenings in conjunction with Oral, Head and Neck Cancer Awareness week, April 2-9. Appointments are available on April 3, April 4 and April 7 at ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyrA7v
via IFTTT

Tonsil Cancer Survivor Shares Story to Raise Awareness - My Panhandle


My Panhandle

Tonsil Cancer Survivor Shares Story to Raise Awareness
My Panhandle
PANAMA CITY, Fla. - Early in 2014, Wanda Barnes was doing her daily skin care routine when she began noticing a lump on her neck. Now, she is sharing her experience battling tonsil cancer in hopes of encouraging others to act quickly if they notice ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovLKnh
via IFTTT

Behind the Scenes: Endo/Exocytosis in the Acquisition of Metastatic Traits

Alterations of endo/exocytic proteins have long been associated with malignant transformation, and genes encoding membrane trafficking proteins have been identified as bona fide drivers of tumorigenesis. Focusing on the mechanisms underlying the impact of endo/exocytic proteins in cancer, a scenario emerges in which altered trafficking routes/networks appear to be preferentially involved in the acquisition of prometastatic traits. This involvement in metastasis frequently occurs through the integration of programs leading to migratory/invasive phenotypes, survival and resistance to environmental stresses, epithelial-to-mesenchymal transition, and the emergence of cancer stem cells. These findings might have important implications in the clinical setting for the development of metastasis-specific drugs and for patient stratification to optimize the use of available therapies. Cancer Res; 77(8); 1–5. ©2017 AACR.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovVbDu
via IFTTT

Energy balance modulation impacts epigenetic reprogramming, ER{alpha} and ER{beta} expression and mammary tumor development in MMTV-neu transgenic mice

The association between obesity and breast cancer risk and prognosis is well established in ER-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis and survival are energy balance-dependent in association with epigenetic reprogramming. Mice were randomized to receive a calorie restriction (CR), overweight (OW)-inducing, or diet-induced obesity (DIO) regimen (n = 27/group). Subsets of mice (n = 4/group/time point) were euthanized after 1, 3 and 5 months to characterize diet-dependent metabolic, transcriptional, and epigenetic perturbations. Remaining mice were followed up to 22 months. Relative to the OW and DIO regimens, CR decreased body weight, adiposity, and serum metabolic hormones as expected, and also elicited an increase in mammary ERα and ERβ expression. Increased DNA methylation accompanied this pattern, particularly at CpG dinucleotides located within binding or flanking regions for the transcriptional regulator CCCTC-binding factor (CTCF) of ESR1 and ESR2, consistent with sustained transcriptional activation of ERα and ERβ. Mammary expression of the DNA methylation enzyme DNMT1 was stable in CR mice but increased over time in OW and DIO mice, suggesting CR obviates epigenetic alterations concurrent with chronic excess energy intake. In the survival study, CR elicited a significant suppression in spontaneous mammary tumorigenesis. Overall, our findings suggest a mechanistic rationale to prevent or reverse excess body weight as a strategy to reduce HER2-positive breast cancer risk.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nDyM2T
via IFTTT

Cholesterol-induced conformation changes in the sterol-sensing domain of the scap protein suggest feedback mechanism to control cholesterol synthesis [Lipids]

Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to reproduce this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here, we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualize with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oDsi58
via IFTTT

Columnar cell variant of papillary thyroid carcinoma: Cytomorphological characteristics of 11 cases with histological correlation and literature review

BACKGROUND

The columnar cell variant of papillary thyroid carcinoma (PTC-CCV) is a rare entity that demonstrates a more aggressive clinical course compared with the more common subtypes of PTC. On histology, it is defined by papillae or gland-like structures lined by columnar cells displaying prominent nuclear stratification. Because to the authors' knowledge no characteristic cytomorphological features have been identified to date and typical features of PTC often are absent on cytology, the diagnosis of PTC-CCV by fine-needle aspiration (FNA) is challenging. This prompted the authors to evaluate a series of PTC-CCV cases to identify features that could facilitate its diagnosis by FNA.

METHODS

A total of 11 surgical specimens of PTC-CCV with corresponding preoperative cytology were identified over a 21-year period. The cytological features of the aspirated specimens, consisting mostly of Papanicolaou and Diff-Quick smears, were evaluated retrospectively.

RESULTS

All cases demonstrated the presence of papillary structures. The most important features observed in PTC-CCV FNA specimens were hypercellularity with nuclear superposition and a paucity of nuclear pseudoinclusions and grooves.

CONCLUSIONS

Although PTC-CCV may demonstrate features that overlap with those of the classic variant of PTC, hypercellular smears with papillary structures covered by cells with pseudostratified nuclei that show a paucity of nuclear pseudoinclusions and grooves should alert the cytopathologist to the possibility of this diagnosis. Cancer Cytopathol 2017. © 2017 American Cancer Society.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovQyJz
via IFTTT

Fludarabine resistance mediated by aminoglycoside-3'-phosphotransferase-IIa and the structurally related eukaryotic cAMP-dependent protein kinase [Research]

While working with G418-resistant stably transfected cells, we realized the neomycin resistance gene (NeoR), which encodes the aminoglycoside-3'-phosphotransferase-IIa [APH(3')-IIa], also confers resistance to the nucleoside analog fludarabine. Fludarabine is a cytostatic drug widely used in the treatment of hematologic and solid tumors as well as in the conditioning of patients before transplantation of hematopoietic progenitors. We present evidence that NeoR-transfected cells do not incorporate fludarabine, thus avoiding DNA damage caused by the drug, evidenced by a lack of FANCD2 monoubiquitination and impaired apoptosis. A screening of other nucleoside analogs revealed that APH(3')-IIa only protects against ATP purine analogs. Moreover, APH(3')-IIa ATPase activity is inhibited by fludarabine monophosphate, suggesting that APH(3')-IIa blocks fludarabine incorporation into DNA by dephosphorylating its active fludarabine triphosphate form. Furthermore, overexpression of the catalytic subunit of the eukaryotic kinase PKA, which is structurally related to APHs, also provides resistance to fludarabine, anticipating its putative utility as a response marker to the drug. Our results preclude the use of Neo marker plasmids in the study of purine analogs and unveils a new resistance mechanism against these chemotherapeuticals.—Sánchez-Carrera, D., Bravo-Navas, S., Cabezón, E., Arechaga, I., Cabezas, M., Yáñez, L., Pipaón, C. Fludarabine resistance mediated by aminoglycoside-3'-phosphotransferase-IIa and the structurally related eukaryotic cAMP-dependent protein kinase.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSHEBQ
via IFTTT

Role of the glucocorticoid-induced leucine zipper gene in dexamethasone-induced inhibition of mouse neutrophil migration via control of annexin A1 expression [Research]

The glucocorticoid-induced leucine zipper gene (GILZ) is a pivotal mediator of the anti-inflammatory effects of glucocorticoids (GCs) that are known to regulate the function of both adaptive and innate immunity cells. Our aim was to investigate the role of GILZ in GC-induced inhibition of neutrophil migration, as this role has not been investigated before. We found that GILZ expression was induced by dexamethasone (DEX), a synthetic GC, in neutrophils, and that it regulated migration of these cells into inflamed tissues under DEX treatment. Of note, inhibition of neutrophil migration was not observed in GILZ knockout mice with peritonitis that were treated by DEX. This was because DEX was unable to up-regulate annexin A1 (Anxa1) expression in the absence of GILZ. Furthermore, we showed that GILZ mediates Anxa1 induction by GC by transactivating Anxa1 expression at the promoter level via binding with the transcription factor, PU.1. The present findings shed light on the role of GILZ in the mechanism of induction of Anxa1 by GCs. As Anxa1 is an important protein for the resolution of inflammatory response, GILZ may represent a new pharmacologic target for treatment of inflammatory diseases.—Ricci, E., Ronchetti, S., Pericolini, E., Gabrielli, E., Cari, L., Gentili, M., Roselletti, E., Migliorati, G., Vecchiarelli, A., Riccardi, C. Role of the glucocorticoid-induced leucine zipper gene in dexamethasone-induced inhibition of mouse neutrophil migration via control of annexin A1 expression.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovTzsQ
via IFTTT

Patient Education Gallbladder Removal Laparoscopic Surgery PreOp®

Patient Education Gallbladder Removal Laparoscopic Surgery PreOp®
https://PreOp.com & https://store.preop.com
Patient Education Company

You may receive a sedative by mouth and

an intravenous line may be put in.

You will then be transferred to the operating table.

In the operating room, a nurse will begin preparation by clipping or shaving the abdomen.

The anesthesiologist will begin to administer anesthesia - most probably general anesthesia.

The surgeon will then apply antiseptic solution to the skin around the area where the incisions will be made,

...place a sterile drape around the operative site. After allowing a few minutes for the anesthetic to take effect ...


...a small incision is made above the umbilicus;

then, a hollow needle will be inserted through the abdominal wall.

And the abdomen will be inflated with carbon dioxide.

An imblical port is created for the laparoscope.

Three more incisions will be made, with care taken to keep the openings as small as possible.

Once in place, the laparoscope will provide video images that allow the surgeon to locate and pull back both the liver and gallbladder...


Next, the surgeon removes the connecting tissue in order to expose the cystic duct and the cystic artery...

Using clips, the surgical teams clamps off both the duct and artery which are later cut to prepare the gallbladder for removal ...

Finally, any remaining tissue connecting the gallbladder to the liver is cut...

The gallbladders is moved into the laparoscopic working port where it is taken out of the body.

All of the instruments are withdrawn ...

the carbon dioxide is allowed to escape...

the muscle layers and other tissues are sewn together, and the skin is closed with sutures or staples.

Finally, sterile dressings are applied.


Patient Education Company



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader https://www.youtube.com/watch?v=9v9vSuy-mCQ
via IFTTT

Wrongness, Responsibility, and Conscientious Refusals in Health Care

Abstract

In this article, I address what kinds of claims are of the right kind to ground conscientious refusals. Specifically, I investigate what conceptions of moral responsibility and moral wrongness can be permissibly presumed by conscientious objectors. I argue that we must permit HCPs to come to their own subjective conclusions about what they take to be morally wrong and what they take themselves to be morally responsible for. However, these subjective assessments of wrongness and responsibility must be constrained in several important ways: they cannot involve empirical falsehoods, objectionably discriminatory attitudes, or unreasonable normative beliefs. I argue that the sources of these constraints are the basic epistemic, relational, and normative competencies needed to function as a minimally decent health-care professional. Finally, I consider practical implications for my framework, and argue that it shows us that the objection raised by the plaintiffs in Zubik v. Burwell is of the wrong sort.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovNzRd
via IFTTT

Ethical Considerations of Triage Following Natural Disasters: The IDF Experience in Haiti as a Case Study

Abstract

Natural disasters in populated areas may result in massive casualties and extensive destruction of infrastructure. Humanitarian aid delegations may have to cope with the complicated issue of patient prioritization under conditions of severe resource scarcity. A triage model, consisting of five principles, is proposed for the prioritization of patients, and it is argued that rational and reasonable agents would agree upon them. The Israel Defense Force's humanitarian mission to Haiti following the 2010 earthquake serves as a case study for the various considerations taken into account when designing the ethical-clinical policy of field hospitals. The discussion focuses on three applications: the decision to include an intensive care unit, the decision to include obstetrics and neonatal units, and the treatment policy for compound fractures.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRsNIu
via IFTTT

SVCT-2 Determines the Sensitivity to Ascorbate-induced Cell Death in Cholangiocarcinoma Cell Lines and Patient Derived Xenografts

Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (L-ascorbic acid, ascorbate) in several types of cancer. However, the effect of L-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oDaG9u
via IFTTT

Research progress in advanced melanoma

Melanoma is a malignant tumor with high rate of metastasis and poor prognosis. How melanoma develops and how to treat it will continue to be a hot topic. This review briefly summarizes the mechanism of melanoma development and the latest progress in its treatment.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovxF9l
via IFTTT

Feature Extraction and Classification on Esophageal X-Ray Images of Xinjiang Kazak Nationality

Esophageal cancer is one of the fastest rising types of cancers in China. The Kazak nationality is the highest-risk group in Xinjiang. In this work, an effective computer-aided diagnostic system is developed to assist physicians in interpreting digital X-ray image features and improving the quality of diagnosis. The modules of the proposed system include image preprocessing, feature extraction, feature selection, image classification, and performance evaluation. 300 original esophageal X-ray images were resized to a region of interest and then enhanced by the median filter and histogram equalization method. 37 features from textural, frequency, and complexity domains were extracted. Both sequential forward selection and principal component analysis methods were employed to select the discriminative features for classification. Then, support vector machine and K-nearest neighbors were applied to classify the esophageal cancer images with respect to their specific types. The classification performance was evaluated in terms of the area under the receiver operating characteristic curve, accuracy, precision, and recall, respectively. Experimental results show that the classification performance of the proposed system outperforms the conventional visual inspection approaches in terms of diagnostic quality and processing time. Therefore, the proposed computer-aided diagnostic system is promising for the diagnostics of esophageal cancer.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2n5SLuR
via IFTTT

A Qualitative Inquiry into Nursing Students’ Experience of Facilitating Reflection in Clinical Setting

Background and Aim. Reflection is known as a skill that is central to nursing students’ professional development. Due to the importance and the role of reflection in clinical areas of nursing, it is important to know how to achieve it. However, nursing trainers face the challenge of how to help their students to improve reflection in clinical settings. The aim of this study was to investigate the nursing students’ experiences of facilitating reflection during clinical practice. This qualitative study was conducted by qualitative content analysis approach. Twenty nursing students during the second to eighth semester of their educational program were selected for participation using purposive sampling. Data were collected through in-depth semistructured interviews. The interview was transcribed verbatim, and qualitative content analysis was used to analyze the data. From the data analysis, four main themes were extracted. Motivation to reflect, complex experiences, efficient trainer, and effective relations were four main themes obtained from study that, in interaction with each other, had facilitating roles in students’ reflective process on experiences. The findings revealed that the nursing students’ reflection in clinical settings is effective in personal and professional level. Reflection of nursing students depends on motivational and educational factors and these factors increase the quality of care in patients. Furthermore, nursing educators need to create nurturing climate as well as supporting reflective behaviors of nursing students.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyidV4
via IFTTT

Endoscopic Ultrasound-Guided Biliary Drainage Using Self-Expandable Metal Stent for Malignant Biliary Obstruction

Purpose. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been increasingly reported worldwide. However, studies concerning EUS-BD from Mainland China are sporadic. This study aims to investigate the feasibility, efficacy, and safety of EUS-BD using SEMS in a single center from Mainland China. Methods. Between November 2011 and August 2015, 24 patients underwent EUS-BD using a standardized algorithm. Results. Three patients underwent rendezvous technique (RV), 4 underwent hepaticogastrostomy (HGS), and 17 underwent choledochoduodenostomy (CDS). The technical and clinical success rates were 95.8% (23/24) and 100% (23/23), respectively. Mean procedure time for the CDS group (35.9 ± 5.0 min) or HGS group (39.3 ± 5.0 min) was significantly shorter than that for the RV group (64.7 ± 9.1 min) (). Complications (13%) included (1) cholangitis and (2) postprocedure hemorrhage. During the follow-up periods (mean 6.4 months), 22 (91.7%) patients died of tumor progression with mean stent patency of 5.8 ± 2.2 months. Stent occlusion occurred in 2 (8.7%) patients. Conclusion. EUS-BD using SEMS is a feasible, effective, and safe alternative for biliary decompression after failed ERCP. EUS-RV may not be the first-line choice for EUS-BD in a medium volume center. Further evaluation and experience of this method are needed.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2n5WVD0
via IFTTT

On Improving the Performance of Dynamic DCVSL Circuits

This contribution aims at improving the performance of Dynamic Differential Cascode Voltage Switch Logic (Dy-DCVSL) and Enhanced Dynamic Differential Cascode Voltage Switch Logic (EDCVSL) and suggests three architectures for the same. The first architecture uses transmission gates (TG) to reduce the logic tree depth and width, which results in speed improvement. As leakage is a dominant issue in lower technology nodes, the second architecture is proposed by adapting the leakage control technique (LECTOR) in Dy-DCVSL and EDCVSL. The third proposed architecture combines features of both the first and the second architectures. The operation of the proposed architectures has been verified through extensive simulations with different CMOS submicron technology nodes (90 nm, 65 nm, and 45 nm). The delay of the gates based on the first architecture remains almost the same for different functionalities. It is also observed that Dy-DCVSL gates are 1.6 to 1.4 times faster than their conventional counterpart. The gates based on the second architecture show a maximum of 74.3% leakage power reduction. Also, it is observed that the percentage of reduction in leakage power increases with technology scaling. Lastly, the gates based on the third architecture achieve similar leakage power reduction values to the second one but are not able to exhibit the same speed advantage as achieved with the first architecture.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyeI0N
via IFTTT

An Exploration of Traditional Chinese Medicinal Plants with Anti-Inflammatory Activities

In a continuing effort to discover more anti-inflammatory medicinal plants in China, the anti-inflammatory activities of 101 extracts from different parts of 84 traditional medicinal plants were evaluated by a panel of in vitro and in vivo assays. Nuclear factor-kappa B (NF-κB) inhibitory effects were determined by luciferase assay in stably transfected Hela cells. Cytotoxic activities were assessed using the MTT assay. Inhibitory effects on LPS-induced nitric oxide production and proinflammatory mediators were assessed by Griess reaction and Real-Time PCR analysis, respectively. In vivo anti-inflammatory activities were examined by xylene-induced mice ear edema model. In total, 22 extracts showed promising NF-κB inhibitory effects whereas 9 of them did not affect the cell viability. The 9 hit extracts were active in at least one of the subsequently performed in vitro pharmacological test systems. The extract from Hemerocallis minor (root) was selected to perform the in vivo study because it demonstrated significant suppressive effects in all the in vitro assays. Results showed that the extract of Hemerocallis minor (Root) was able to alleviate ear edema effectively in xylene-induced mice ear edema mode. Collectively, our study provides evidence for the potential anti-inflammatory effects of the medicinal plants traditionally used in China. Further phytochemical and pharmacological studies remain to be clarified.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2n5L73z
via IFTTT

Global Attractors of the Extensible Plate Equations with Nonlinear Damping and Memory

We prove in this paper the existence of a global attractor for the plate equations of Kirchhoff type with nonlinear damping and memory using the contraction function method.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nyeHdf
via IFTTT

PV-Powered CoMP-Based Green Cellular Networks with a Standby Grid Supply

This paper proposes a novel framework for PV-powered cellular networks with a standby grid supply and an essential energy management technique for achieving envisaged green networks. The proposal considers an emerging cellular network architecture employing two types of coordinated multipoint (CoMP) transmission techniques for serving the subscribers. Under the proposed framework, each base station (BS) is powered by an individual PV solar energy module having an independent storage device. BSs are also connected to the conventional grid supply for meeting additional energy demand. We also propose a dynamic inter-BS solar energy sharing policy through a transmission line for further greening the proposed network by minimizing the consumption from the grid supply. An extensive simulation-based study in the downlink of a Long-Term Evolution (LTE) cellular system is carried out for evaluating the energy efficiency performance of the proposed framework. System performance is also investigated for identifying the impact of various system parameters including storage factor, storage capacity, solar generation capacity, transmission line loss, and different CoMP techniques.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2n60CIW
via IFTTT

The role of illicit, licit, and designer drugs in the traffic in Hungary

Driving under the influence of illicit and licit drugs (DUID) has been punishable in Hungary since July 1999. According to data from Country Police Headquarters approximately 10-15,000 alcohol impairment cases per year were taken to court between 2000 and 2010 (personal communication) but drug impairment was proven in less than 120 cases per year [1]. The real number of DUID cases, however, is probably much higher. A roadside survey demonstrating a higher incidence of DUID was conducted (DRUID EU-6 project) in Csongrád County (South-East Hungary,∼420 000 inhabitants), during which oral fluid samples of 2738 randomly stopped car drivers were analyzed for illicit and licit drugs in 2008-2009.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRaS4V
via IFTTT

A fully synthetic lung model for wound-ballistic experiments − first results

Due to the complexity of bullet-tissue interaction, the field of wound-ballistics still strongly relies on experiments in order to understand the injuring capacity of a certain ammunition type, e.g. the wound profile. The wound profile refers to the penetration depth, the bullet deformation/fragmentation, the diameter of the permanent and the temporary wound cavity.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nV9JL2
via IFTTT

Aged patients with metastatic castration resistant prostate cancer: should we treat with chemotherapy?

As industrialized populations get older and life expectancy increases, the number and proportion of elderly patients with cancer is rising, and this trend is expected to continue in the western and industrialized world. More than half of new cancers occur in the elderly. Prostate cancer is a disease largely affecting older men. Median age at diagnosis is 67years, with 70.6% of prostate cancer deaths occurring in men older than75 [1]. Moreover, prostate cancer is the most frequently diagnosed cancer in men in both the USA [2] and Europe [3], and one of the three most common causes of cancer-related death.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSWAQw
via IFTTT

Aged patients with metastatic castration resistant prostate cancer: should we treat with chemotherapy?

As industrialized populations get older and life expectancy increases, the number and proportion of elderly patients with cancer is rising, and this trend is expected to continue in the western and industrialized world. More than half of new cancers occur in the elderly. Prostate cancer is a disease largely affecting older men. Median age at diagnosis is 67years, with 70.6% of prostate cancer deaths occurring in men older than75 [1]. Moreover, prostate cancer is the most frequently diagnosed cancer in men in both the USA [2] and Europe [3], and one of the three most common causes of cancer-related death.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSWAQw
via IFTTT

Cortical auditory evoked potentials in children who stutter

It has been hypothesized that impaired auditory processing influence the occurrence of stuttering. Also, it is suggested that speech perception in children who stutter differed from normal. Auditory processing should be investigated in children who stutter shortly after the onset of stuttering in order to evaluate the extent to which impaired auditory processing contributes to the development of stuttering. CAEPs provide the necessary temporal and spatial resolution to detect differences in auditory processing and the neural activity that is related or time-locked to the auditory stimulus.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nD9XUz
via IFTTT

PPARG is central to the initiation and propagation of human angiomyolipoma, suggesting its potential as a therapeutic target

Angiomyolipoma (AML), the most common benign renal tumor, can result in severe morbidity from hemorrhage and renal failure. While mTORC1 activation is involved in its growth, mTORC1 inhibitors fail to eradicate AML, highlighting the need for new therapies. Moreover, the identity of the AML cell of origin is obscure. AML research, however, is hampered by the lack of in vivo models. Here, we establish a human AML-xenograft (Xn) model in mice, recapitulating AML at the histological and molecular levels. Microarray analysis demonstrated tumor growth in vivo to involve robust PPARG-pathway activation. Similarly, immunostaining revealed strong PPARG expression in human AML specimens. Accordingly, we demonstrate that while PPARG agonism accelerates AML growth, PPARG antagonism is inhibitory, strongly suppressing AML proliferation and tumor-initiating capacity, via a TGFB-mediated inhibition of PDGFB and CTGF. Finally, we show striking similarity between AML cell lines and mesenchymal stem cells (MSCs) in terms of antigen and gene expression and differentiation potential. Altogether, we establish the first in vivo human AML model, which provides evidence that AML may originate in a PPARG-activated renal MSC lineage that is skewed toward adipocytes and smooth muscle and away from osteoblasts, and uncover PPARG as a regulator of AML growth, which could serve as an attractive therapeutic target.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovD6oU
via IFTTT

Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations

Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P << 10–10), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53-mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSS4RX
via IFTTT

Supraphysiological levels of GDF11 induce striated muscle atrophy

Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor β superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the in vivo effects of GDF11 on skeletal muscle mass have not been addressed. Using in vitro myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities/potencies on activating p-SMAD2/3 and induce comparable levels of differentiated myotube atrophy. We further demonstrate that adeno-associated virus-mediated systemic overexpression of GDF11 in C57BL/6 mice results in substantial atrophy of skeletal and cardiac muscle, inducing a cachexic phenotype not seen in mice expressing similar levels of Mstn. Greater cardiac expression of Tgfbr1 may explain this GDF11-specific cardiac phenotype. These data indicate that bioactive GDF11 at supraphysiological levels cause wasting of both skeletal and cardiac muscle. Rather than a therapeutic agent, GDF11 should be viewed as a potential deleterious biomarker in muscle wasting diseases.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovtGK5
via IFTTT

Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts

c-MYC controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient-derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC-low subgroup. To define classifier expression signature, we selected a group of 10 MYC target transcripts which expression is increased in the MYC-high group and six transcripts increased in the MYC-low group. We validated the ability of these markers panel to identify MYC-high patient-derived xenografts from both: discovery and validation cohorts as well as primary cell cultures from the same patients. We then showed that cells from MYC-high patients are more sensitive to JQ1 treatment compared to MYC-low cells, in monolayer, 3D cultured spheroids and in vivo xenografted tumors, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSzFog
via IFTTT

Faecal microbiota transplantation protects against radiation-induced toxicity

Severe radiation exposure may cause acute radiation syndrome, a possibly fatal condition requiring effective therapy. Gut microbiota can be manipulated to fight against many diseases. We explored whether intestinal microbe transplantation could alleviate radiation-induced toxicity. High-throughput sequencing showed that gastrointestinal bacterial community composition differed between male and female mice and was associated with susceptibility to radiation toxicity. Faecal microbiota transplantation (FMT) increased the survival rate of irradiated animals, elevated peripheral white blood cell counts and improved gastrointestinal tract function and intestinal epithelial integrity in irradiated male and female mice. FMT preserved the intestinal bacterial composition and retained mRNA and long non-coding RNA expression profiles of host small intestines in a sex-specific fashion. Despite promoting angiogenesis, sex-matched FMT did not accelerate the proliferation of cancer cells in vivo. FMT might serve as a therapeutic to mitigate radiation-induced toxicity and improve the prognosis of tumour patients after radiotherapy.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovCVtY
via IFTTT

Ethics of stem cell-derived gametes made in a dish: fertility for everyone?



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSVaW9
via IFTTT

Sodium permeable and "hypersensitive" TREK-1 channels cause ventricular tachycardia

In a patient with right ventricular outflow tract (RVOT) tachycardia, we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1. In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovAjfm
via IFTTT

Gene signature driving invasive mucinous adenocarcinoma of the lung

Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin-producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1/B7-H4 (but not PD-L1/B7-H1). Importantly, induction of FOXA3 or SPDEF along with mutant KRAS in lung epithelium was sufficient to develop benign or malignant mucinous lung tumors, respectively, in transgenic mice. FOXA3 and SPDEF induced MUC5AC and MUC5B, while HNF4A induced MUC3 in human mucinous lung cancer cells harboring a KRAS mutation. ChIP-seq combined with CRISPR/Cas9 determined that upstream enhancer regions of the mucin genes MUC5AC and MUC5B, which were bound by SPDEF, were required for the expression of the mucin genes. Here, we report the molecular signature and gene regulatory network driving mucinous lung tumors.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSOF5N
via IFTTT

Sodium leak through K2P potassium channels and cardiac arrhythmia, an emerging theme

In this issue of EMBO Molecular Medicine, Decher et al (2017) identify a point mutation in the K2P2 (TREK-1) potassium (K+) channel that changes function in just those ways expected to predispose to right ventricular outflow tract (RVOT) ventricular tachycardia (VT) in the patient they study. Whereas wild-type channels are selective for K+ and inhibited by β-adrenergic stimulation, mutant I267T channels pass sodium (Na+) into the cells, even during β-adrenergic stimulation, and are more active in response to membrane stretch, changes predicted to enhance cardiac myocyte excitability. The report contributes to accumulating evidence for Na+ leak via K2P channels in association with normal development (Thomas et al, 2008), acquired arrhythmia (Ma et al, 2011), and now a missense mutation. Decher et al (2017) both inform and direct us toward interesting opportunities for further investigation.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovtCdj
via IFTTT

SK4 K+ channels are therapeutic targets for the treatment of cardiac arrhythmias

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice. TRAM-34, a selective blocker of SK4 channels, prominently reduced delayed afterdepolarizations and arrhythmic Ca2+ transients observed following application of the β-adrenergic agonist isoproterenol in CPVT2-derived hiPSC-CMs and in SAN cells from KI mice. Strikingly, in vivo ECG recording showed that intraperitoneal injection of the SK4 channel blockers, TRAM-34 or clotrimazole, greatly reduced the arrhythmic features of CASQ2-D307H KI and CASQ2 knockout mice at rest and following exercise. This work demonstrates the critical role of SK4 Ca2+-activated K+ channels in adult pacemaker function, making them promising therapeutic targets for the treatment of cardiac ventricular arrhythmias such as CPVT.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSGdnc
via IFTTT

Moving molecular medicine

Incoming Chief Editor Philippe Sansonetti shares his vision of the role of the journal in the burgeoning areas of molecular medicine.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovJOve
via IFTTT

A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Recent studies highlight the emergence of multidrug-resistant K. pneumoniae strains which show resistance to colistin, a last-line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB-associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an mgrB gene K. pneumoniae mutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mgrB mutation induces PhoPQ-governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSPgUP
via IFTTT

Defining the RNaseH2 enzyme-initiated Ribonucleotide Excision Repair Pathway in Archaea [Enzymology]

Incorporation of ribonucleotides during DNA replication has severe consequences for genome stability. Although eukaryotes possess a number of redundancies for initiating and completing repair of misincorporated ribonucleotides, archaea such as Thermococcus rely only upon RNaseH2 to initiate the pathway. Because Thermococcus DNA polymerases incorporate as many as 1,000 ribonucleotides per genome, RNaseH2 must be efficient at recognizing and nicking at embedded ribonucleotides to ensure genome integrity. Here, we show that ribonucleotides are incorporated by the hyperthermophilic archaeon Thermococcus kodakarensis both in vitro and in vivo and a robust ribonucleotide excision repair pathway is critical to keeping incorporation levels low in wild-type cells. Using pre-steady-state and steady-state kinetics experiments, we also show that archaeal RNaseH2 rapidly cleaves at embedded ribonucleotides (200 - 450 s-1), but exhibits an approximately 1,000-fold slower turnover rate (0.06 - 0.17 s-1), suggesting a potential role for RNaseH2 in protecting or marking nicked sites for further processing. We found that following RNaseH2 cleavage, the combined activities of polymerase B (PolB), flap endonuclease (Fen1), and DNA Ligase are required to complete ribonucleotide processing. PolB formed a ribonucleotide-containing flap by strand displacement synthesis that was cleaved by Fen1, and DNA ligase sealed the nick for complete repair. Our study reveals conservation of the overall mechanism of ribonucleotide excision repair across domains of life. The lack of redundancies in ribonucleotide repair in archaea perhaps suggests a more ancestral form of ribonucleotide excision repair compared with the eukaryotic pathway.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nR3JS1
via IFTTT

Heat Shock Protein 104 (Hsp104) mediated Curing of [PSI+] Yeast Prions Depends on Both [PSI+] Conformation and the Properties of the Hsp104 Homologs [Protein Structure and Folding]

Prions arise from proteins that have two possible conformations: properly folded and non-infectious, or misfolded and infectious. The [PSI+] yeast prion, which is the misfolded, self-propagating form of the translation termination factor eRF3 (Sup35), can be cured of its infectious conformation by overexpression of Hsp104, which helps dissolve the prion seeds. This dissolution depends on the trimming activity of Hsp104, which reduces the size of the prion seeds without increasing their number. To further understand the relationship between trimming and curing, trimming was followed by measuring the loss of GFP-labeled Sup35 foci from both strong and weak [PSI+] variants; the former variant has more seeds and less soluble Sup35 than the latter. Overexpression of Saccharomyces cerevisiae Hsp104 (Sc-Hsp104) both trimmed the weak [PSI+] variants much faster than the strong variants and cured the weak variants an order of magnitude faster than the strong variants. Overexpression of the fungal Hsp104 homologs from Schizosaccharomyces pombe (Sp-Hsp104) or Candida albicans (Ca-Hsp104) also trimmed and cured the weak variants, but, interestingly, neither trimmed nor cured the strong variants. These results show that, because Sc-Hsp104 has greater trimming activity than either Ca-Hsp104 or Sp-Hsp104, it cures both the weak and strong variants, whereas Ca-Hsp104 and Sp-Hsp104 only cure the weak variants. Therefore, curing by Hsp104 overexpression depends on both the trimming ability of the fungal Hsp104 homolog and the strength of the [PSI+] variant; the greater the trimming activity of the Hsp104 homolog and the weaker the variant, the greater the curing.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVirsJ
via IFTTT

Metformin Directly Binds the Alarmin HMGB1 and Inhibits its Proinflammatory Activity [Signal Transduction]

Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is therefore a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1, but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model, in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1 neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRhHU0
via IFTTT

An Immunoaffinity-Based Method for Isolating Ultrapure Adult Astrocytes Based on ATP1B2 Targetting by the ACSA-2 Antibody. [Neurobiology]

Astrocytes are a major cell type in the mammalian central nervous system (CNS). Astrocytes are now known to play a number of essential roles in processes including synapse formation and function, as well as blood brain barrier formation and control of cerebral blood flow. However, our understanding of the molecular mechanisms underlying astrocyte development and function is still rudimentary (1). This lack of knowledge is at least partly due to the lack of tools currently available for astrocyte biology. ACSA-2 is a commercially available antibody originally developed for the isolation of astrocytes from young postnatal mouse brain, using magnetic cell sorting methods, but its utility in isolating cells from adult tissue has not yet been published. Using a modified protocol, we now show that this tool can also be used to isolate ultrapure astrocytes from adult brain. Furthermore, using a variety of techniques (including single cell sequencing, overexpression and knockdown assays, immunoblotting and immunohistochemistry), we identify the ACSA-2 epitope for the first time as ATP1B2, and characterize its distribution in the CNS. Finally, we show that ATP1B2 is stably expressed in multiple models of CNS injury and disease. Hence, we show that the ACSA-2 antibody possesses the potential to be an extremely valuable tool for astrocyte research allowing the purification and characterization of astrocytes (potentially including injury and disease models) without the need for any specialized and expensive equipment. In fact, our results suggest ACSA-2 should be a first choice method for astrocyte isolation and characterization.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVt4Md
via IFTTT

A Sensitive Assay Reveals Structural Requirements for Alpha-Synuclein Fibril Growth [Protein Structure and Folding]

The accumulation of alpha-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathological process in Parkinson disease (PD). A pathogenic role for α-syn fibril accumulation is supported by the identification of dominantly inherited α-syn (SNCA) gene mutations in rare cases of familial PD. Fibril formation involves a spontaneous nucleation event in which soluble α-syn monomers associate to form seeds, followed by fibril growth during which monomeric α-syn molecules sequentially associate with existing seeds. To better investigate this process, we developed sensitive assays that use the fluorescein arsenical dye FlAsH, to detect soluble oligomers and mature fibrils formed from recombinant α-syn protein containing an N-terminal bicysteine tag (C2-α-syn). Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (i.e., H50Q and A53T) greatly increased growth rates, while others (E46K, A30P and G51D) decreased growth rates. Experiments with wild-type seeds extended by mutant monomer and vice versa revealed that single amino acid differences between seed and monomer proteins consistently decreased growth rates. These results demonstrate that α-syn monomer association during fibril growth is a highly ordered process that can be disrupted by misalignment of individual amino acids, and that only a subset of familial PD mutations causes fibril accumulation through increased fibril growth rates. The SeGMA assays reported herein can be utilized to further elucidate structural requirements of α-syn fibril growth and to identify growth inhibitors as a potential therapeutic approach in PD.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRecge
via IFTTT

Flavones modulate respiratory epithelial innate immunity: anti-inflammatory effects and activation of T2R14 [Signal Transduction]

Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ~20% of adult antibiotic prescriptions in the US. Due to the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potential important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and iNOS upregulation as well as cytokine release in primary and cultured airway cells in response several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (<7 nm) with the T2R38 isoform. Heterologously-expressed T2R14 responds to multiple flavones. These flavones also activate T2R14-driven calcium signals in primary cells that activate nitric oxide production to increase ciliary beating and mucociliary clearance. T2R14 responses were not affected by TAS2R38 polymorphisms encoding functional (PAV) or non-functional (AVI) T2R38. Our data demonstrate that T2R14 in sinonasal cilia is a potential therapeutic target for upper respiratory infections, and that flavones may have clinical potential as topical therapeutics, particularly in T2R38 AVI/AVI individuals.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVd64N
via IFTTT

Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester [Lipids]

Reverse cholesterol transport (RCT) - transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver - is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process - gobbling, i.e., one-step transfer of all HDL-CE to the cell and nibbling, multiple successive cycles of SR-B1-HDL association during which a few CE transfer to the cell. Concurrently, we compared cellular uptake of apo AI with that of apo AII, which is more lipophilic than apo AI, using HDL-[3H]CE labeled with [125I]apo AI or [125I]apo AII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR-/-) with (CHO-SR-B1) and without SR-B1 over expression, and in human Huh7 hepatocytes. Relative to CE, both apo AI and apo AII were excluded from uptake by all cells. However, apo AII was more highly excluded from uptake (2-4x) than apo AI. To distinguish gobbling vs. nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size exclusion chromatography, and the distribution of apo AI, apo AII, cholesterol and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e., nibbling, with the concurrent release of lipid-free apo AI; apo AII was retained in an HDL remnant. Our data support a SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apo AI leaving an apo AII-rich remnant.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRgMTD
via IFTTT

Pathogenic Acinetobacter Species have a Functional Type I Secretion System and Contact-Dependent Inhibition Systems [Genomics and Proteomics]

Pathogenic Acinetobacter species, including A. baumannii and A. nosocomialis, are opportunistic human pathogens of increasing relevance worldwide. Although their mechanisms of drug resistance are well studied, the virulence factors that govern Acinetobacter pathogenesis are incompletely characterized. Here we define the complete secretome of A. nosocomialis strain M2 in minimal media and demonstrate that pathogenic Acinetobacter species produce both a functional type I secretion system (T1SS) and a contact dependent inhibition (CDI) system. Using bioinformatics, quantitative proteomics, and mutational analyses we show that Acinetobacter uses its T1SS for exporting two putative T1SS effectors, an RTX-Serralysin-like toxin and the biofilm associated protein (Bap). Moreover, we found that mutation of any component of the T1SS system abrogated type VI secretion activity under nutrient-limited conditions, indicating a previously unrecognized crosstalk between these two systems. We also demonstrate that the Acinetobacter T1SS is required for biofilm formation. Lastly, we show that both A. nosocomialis and A. baumannii produce functioning CDI systems that mediate growth inhibition of sister cells lacking the cognate immunity protein. The Acinetobacter CDI systems are widely distributed across pathogenic Acinetobacter species, with many A. baumannii isolates harboring two distinct CDI systems. Collectively, these data demonstrate the power of differential, quantitative proteomics approaches to study secreted proteins, define the role of previously uncharacterized protein export systems, and observe crosstalk between secretion systems in the pathobiology of medically relevant Acinetobacter. The data are available via ProteomeXchange with identifier PXD005881.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nV37N4
via IFTTT

Distinct domains of the {beta}1-subunit cytosolic N-terminus control surface expression and functional properties of large conductance calcium-activated potassium (BK) channels [Membrane Biology]

The properties and function of large conductance calcium- and voltage- activated potassium (BK) channels are modified by the tissue specific expression of regulatory β 1-subunits. Although the short cytosolic N-terminal domain of the β 1-subunit is important for controlling both BK channel trafficking and function, whether the same, or different, regions of the N-terminus control these distinct processes remain unknown. Here we demonstrate that the first six N-terminal residues, including K3, K4 and L5, are critical for controlling functional regulation, but not trafficking, of BK channels. This membrane distal region has features of an amphipathic helix that is predicted to control the orientation of the first transmembrane segment (TM1) of the β 1-subunit. In contrast, a membrane proximal leucine residue (L17) controls trafficking without affecting functional coupling, an effect that is in part dependent on controlling efficient ER exit of the pore-forming α-subunit. Thus cell surface trafficking and functional coupling with BK channels are controlled by distinct domains of the β 1-subunit N-terminus.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRimEO
via IFTTT

Some head and neck cancer patients benefit from continued checkpoint inhibitor treatment - Medical Xpress


Medical Xpress

Some head and neck cancer patients benefit from continued checkpoint inhibitor treatment
Medical Xpress
New research suggests that some patients with head and neck cancers can benefit by continuing treatment with an immunotherapy drug after their tumors show signs of enlargement according to investigators at Dana-Farber Cancer Institute. Credit: DFCI.

and more »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVblVc
via IFTTT

The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective

Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years.VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSoLyQ
via IFTTT

Xylitol nasal irrigation in the treatment of chronic rhinosinusitis

To evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovzLpm
via IFTTT

The role of illicit, licit, and designer drugs in the traffic in Hungary

Driving under the influence of illicit and licit drugs (DUID) has been punishable in Hungary since July 1999. According to data from Country Police Headquarters approximately 10-15,000 alcohol impairment cases per year were taken to court between 2000 and 2010 (personal communication) but drug impairment was proven in less than 120 cases per year [1]. The real number of DUID cases, however, is probably much higher. A roadside survey demonstrating a higher incidence of DUID was conducted (DRUID EU-6 project) in Csongrád County (South-East Hungary,∼420 000 inhabitants), during which oral fluid samples of 2738 randomly stopped car drivers were analyzed for illicit and licit drugs in 2008-2009.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nRaS4V
via IFTTT

A fully synthetic lung model for wound-ballistic experiments − first results

Due to the complexity of bullet-tissue interaction, the field of wound-ballistics still strongly relies on experiments in order to understand the injuring capacity of a certain ammunition type, e.g. the wound profile. The wound profile refers to the penetration depth, the bullet deformation/fragmentation, the diameter of the permanent and the temporary wound cavity.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nV9JL2
via IFTTT

SVCT-2 Determines the Sensitivity to Ascorbate-induced Cell Death in Cholangiocarcinoma Cell Lines and Patient Derived Xenografts

Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (L-ascorbic acid, ascorbate) in several types of cancer. However, the effect of L-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oDaG9u
via IFTTT

Research progress in advanced melanoma

Melanoma is a malignant tumor with high rate of metastasis and poor prognosis. How melanoma develops and how to treat it will continue to be a hot topic. This review briefly summarizes the mechanism of melanoma development and the latest progress in its treatment.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovxF9l
via IFTTT

Orange Regional offers free cancer screenings | Warwick ... - The Warwick Advertiser


Orange Regional offers free cancer screenings | Warwick ...
The Warwick Advertiser
MIDDLETOWN — Orange Regional Medical Center will offer the community free oral, head and neck cancer screenings in conjunction with Oral, Head and ...

and more »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSMqPR
via IFTTT

Holzer offering free cancer screenings - Gallipolis Daily Tribune


Gallipolis Daily Tribune

Holzer offering free cancer screenings
Gallipolis Daily Tribune
About Oral Head and Neck Cancer Most oral cancers arise on the lips, tongue or the floor of the mouth. They also may occur inside the cheeks, on the gums or on the roof of the mouth. Oropharyngeal cancers related to HPV are often found in the tonsil or ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2n5OW8U
via IFTTT

Nine in ten older children miss five-a-day target - Daily Mail


Daily Mail

Nine in ten older children miss five-a-day target
Daily Mail
The charity, which has launched a new recipe website, said the figures were 'seriously worrying' as a diet low in fruit and vegetables could increase a person's risk of lung, mouth, pharynx and larynx cancer in later life. Meanwhile, only 29 per cent ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSBnq1
via IFTTT

Holzer offering free cancer screenings - Gallipolis Daily Tribune


Gallipolis Daily Tribune

Holzer offering free cancer screenings
Gallipolis Daily Tribune
Oral, Head, and Neck Cancer Awareness Week® is annually recognized in April, and this free screening aims to catch cancers that arise in the nasal cavity, sinuses, lips, mouth, thyroid glands, salivary glands, throat or larynx (voice box) at an early ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2oSumWe
via IFTTT

Holzer offering free cancer screenings - Gallipolis Daily Tribune


Gallipolis Daily Tribune

Holzer offering free cancer screenings
Gallipolis Daily Tribune
About Oral Head and Neck Cancer Most oral cancers arise on the lips, tongue or the floor of the mouth. They also may occur inside the cheeks, on the gums or on the roof of the mouth. Oropharyngeal cancers related to HPV are often found in the tonsil or ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nCYGUf
via IFTTT

Drawing Out a Sabercat's Smile

Contrary to a popular paleoart trend, Smilodon didn't have a mushy bulldog face.

-- Read more on ScientificAmerican.com
feed?d=yIl2AUoC8zA feed?d=qj6IDK7rITs feed?i=3hIplM80abY:4C0szhnHYYs:gIN9vFwOq feed?d=l6gmwiTKsz0 feed?d=ZC7T4KBF6Nw feed?d=I9og5sOYxJI feed?d=xQlvkV3S7Ew


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovMCbo
via IFTTT

Cancer Researchers Detail Efforts to 'Discover, Predict, Prevent ... - GenomeWeb


Cancer Researchers Detail Efforts to 'Discover, Predict, Prevent ...
GenomeWeb
Speakers at the conference's opening plenary showed how their work in cancer research fit into the broad theme of 'Discover, Predict, Prevent, Treat.'

and more »


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ovFxYl
via IFTTT

Lignocellulosic sugar management for xylitol and ethanol fermentation with multiple cell recycling by Kluyveromyces marxianus IIPE453

S09445013.gif

Publication date: Available online 3 April 2017
Source:Microbiological Research
Author(s): Diptarka Dasgupta, Debashish Ghosh, Sheetal Bandhu, Dilip K. Adhikari
Optimum utilization of fermentable sugars from lignocellulosic biomass to deliver multiple products under biorefinery concept has been reported in this work. Alcohol fermentation has been carried out with multiple cell recycling of Kluyveromyces marxianus IIPE453. The yeast utilized xylose-rich fraction from acid and steam treated biomass for cell generation and xylitol production with an average yield of 0.315±0.01g/g while the entire glucose rich saccharified fraction had been fermented to ethanol with high productivity of 0.9±0.08g/L/h. A detailed insight into its genome illustrated the strain’s complete set of genes associated with sugar transport and metabolism for high-temperature fermentation. A set flocculation proteins were identified that aided in high cell recovery in successive fermentation cycles to achieve alcohols with high productivity. We have brought biomass derived sugars, yeast cell biomass generation, and ethanol and xylitol fermentation in one platform and validated the overall material balance. 2 Kg sugarcane bagasse yielded 193.4g yeast cell, and with multiple times cell recycling generated 125.56g xylitol and 289.2g ethanol (366ml).



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nUUdz4
via IFTTT

Holzer offering free cancer screenings - Gallipolis Daily Tribune


Gallipolis Daily Tribune

Holzer offering free cancer screenings
Gallipolis Daily Tribune
Oral, Head, and Neck Cancer Awareness Week® is annually recognized in April, and this free screening aims to catch cancers that arise in the nasal cavity, sinuses, lips, mouth, thyroid glands, salivary glands, throat or larynx (voice box) at an early ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVmENh
via IFTTT

Holzer offering free cancer screenings - Gallipolis Daily Tribune


Gallipolis Daily Tribune

Holzer offering free cancer screenings
Gallipolis Daily Tribune
Oral, Head, and Neck Cancer Awareness Week® is annually recognized in April, and this free screening aims to catch cancers that arise in the nasal cavity, sinuses, lips, mouth, thyroid glands, salivary glands, throat or larynx (voice box) at an early ...



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nQZSo0
via IFTTT

Short- and Long-term Progress of Recurrent Laryngeal Nerve Paralysis After Subtotal Esophagectomy

Aim: To clarify risk factors and long-term progress of postoperative recurrent laryngeal nerve paralysis (PRNP) in patients with esophageal cancer. Patients and Methods: One hundred and twenty-five esophageal cancer patients, who underwent subtotal esophagetomy, including recurrent laryngeal nerve lymphadenectomy, were analyzed. A laryngoscopy was routinely performed to assess the motility of vocal cords. Results: PRNP was detected in 79 patients and 26 (20.8%) patients required medical interventions (Grade II or more by the Clavien-Dindo classification; group II). Forty-one of 66 (62.1%) patients recovered from PRNP with a median postoperative time of 135 days. The three-field lymphadenectomy and long operative time were the independent prognostic factors of group II. Conclusion: Radical operation caused PRNP with grade II or more. The long-term follow-up of vocal cords was necessary to detect patients with either transient or permanent PRNP.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nR3yWV
via IFTTT

Antitumor and Cancer-preventative Function of Fucoxanthin: A Marine Carotenoid

Fucoxanthin is a marine carotenoid mainly found in brown seaweeds. Its antitumor and cancer-preventative function has been extensively investigated. Investigations have indicated that fucoxanthin and its metabolite fucoxanthinol induce G1 cell-cycle arrest and apoptosis in various cell lines and can inhibit cancer development in animal models. It is imperative that the underlying mechanism of action of fucoxanthin be elucidated in order to facilitate the development of cancer-prevention strategies in humans. Key molecules that require consideration include mitogen-activated protein kinase, growth arrest and DNA damage-inducible 45, AP-1 transcription factor, nuclear factor-kappa B and several others, including cell cycle-related molecules for G1 cell-cycle arrest and the B cell lymphoma-2 family, X-linked inhibitor of apoptosis, cellular inhibitor of apoptosis protein and AKT serine/threonine kinase/phosphatidylinositol-3-kinase for apoptosis. In this review, the mechanisms by which fucoxanthin exerts its antitumor and cancer-preventative action in cell lines and mouse models is discussed, in addition to the potential use of fucoxanthin as a promising compound for cancer prevention.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nUUOk6
via IFTTT

A Locally Advanced Breast Cancer that Achieved pCR with Pertuzumab, Trastuzumab and Docetaxel: Case Report

We herein report a case of locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that achieved a pathological complete response (pCR) with pertuzumab, trastuzumab and docetaxel therapy. A 70-year-old female presented with an elastic hard mass, 5.0 cm in diameter with broad redness and edema of the skin in her right breast. Swollen lymph nodes were also recognized in the right axilla. The pathological diagnosis was invasive ductal carcinoma and its biological character was estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, HER2 3+ and Ki-67 index 60%. The patient was finally diagnosed with primary unresectable, locally advanced breast cancer and started on pertuzumab, trastuzumab and docetaxel combination therapy. The tumor subsequently reduced in size and, after 4 cycles of this therapy, she underwent surgery. The histopathological examination of the postoperative specimen showed pCR in both the primary tumor and axillary lymph nodes.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nQWJom
via IFTTT

Detection of Free Cancer Cells in Pelvic Lavage with Double Immunocytochemistry at Rectal Cancer Surgery

Background/Aim: The aim of the present study was to describe a double immunocytochemical staining method for detecting free cancer cells after rectal cancer surgery and to evaluate their extent and prognostic role. Materials and Methods: Immunocytochemistry was performed using antibodies against cytokeratin 20/caudal-typehomeobox transcription factor 2 (CDX2) and mucin glycoprotein-2 (MUC2)/p53 protein. The study included 29 patients with infraperitoneal rectal cancer who underwent bowel resection and four controls. The pelvic lavage was retrieved at the start of laparotomy, after total mesorectal excision and after abdominal lavage with sterile water. Results: Free cancer cells were detected with the double immunocytochemical method in the two controls with carcinomatosis and one control with sigmoidal cancer. None of the patients with rectal tumours had presence of free cancer cells. Conclusion: Immunocytochemical analysis of peritoneal lavage was feasible and negative in patients with infraperitoneal rectal cancer. Further studies are encouraged to investigate the clinical relevance in cases with free cancer cells after incomplete total mesorectal excision.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nUPdKO
via IFTTT

Chemoembolization with Drug-eluting Microspheres Loaded with Doxorubicin for the Treatment of Cholangiocarcinoma

Aim: To report clinical outcomes of transarterial chemoembolization (TACE) using drug-eluting beads (DEBs) loaded with doxorubicin for the treatment of unresectable intrahepatic cholangiocarcinoma (CCA). Patients and Methods: We treated 127 patients with doxorubicin via TACE. Inclusion criteria were: diagnosis of unresectable CCA; indication for TACE, performance status (PS) 0-2, >3 months of life expectancy, >18 years old, written consent. TACE was performed using DEBs for 109 (86%) patients and polythylene glycol drug-elutable microspheres (PEG) loaded with doxorubicin for 18 (14%) patients. Results: Tumor response of the whole sample of 127 patients was partial response (PR) in 19 (15%) patients, stable disease (SD) in 101 (80%) and progressive disease (PD) in seven (5%) 3 months after therapy, with no complete responses. There were differences between type of embolics: PR was 7% and 77%, SD was 88% and 8%, and PD was 5% and 15%, and the disease control rate was 95% and 85% in the DEB and PEG groups, respectively. Most frequent side-effects were: abdominal pain, fever, nausea, and transaminase rise. Conclusion: TACE was effective and safe for CCA treatment, with a high disease control rate. The best response of PEG-TACE was PR, whereas it was SD for DEB-TACE.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nR5kaJ
via IFTTT

On-site Cytology for Development of Patient-Derived Three-dimensional Organoid Cultures - A Pilot Study

Background/Aim: Development of patient-derived three-dimensional (3D) organoid cultures is an emerging technique in the field of precision oncology. We aimed to integrate on-site adequacy evaluation using cytology into the tumor organoid development workflow to ensure precise characterization and growth of these cultures. Patients and Methods: Cancer patients were consented to a Precision Medicine trial. Fresh tissue was procured for genomic analyses as well as organoid development. Fresh tissue destined for organoid development was evaluated by preparing on-site cytology smears to ensure that only lesional tissue would be submitted for further cell culture work. Results: Cytology preparations were made from 64 different tumor samples and evaluated prior to tissue submission for organoid development. In 53 (82.2%) of those tumor samples, the cytology preparation was diagnostic, thus providing adequate material for organoid development. Conclusion: Characterizing the tissue prior to submission for organoid development ensures submission of lesional tissue only. Furthermore, it is a cost-effective method that can help document patient diagnosis. This can be of importance in biopsies, since the tissue submitted for organoid development cannot be retrieved for clinical diagnosis afterwards. Our findings in this pilot study led to the implementation of on-site cytological evaluation in the tumor organoid development workflow at the Englander Institute for Precision Medicine, NY, USA.



from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nVaKTr
via IFTTT

Δημοφιλείς αναρτήσεις