Management of Large-Volume Subperiosteal Abscesses of the Orbit: Medical vs Surgical Outcomes

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Critical Airway Team: A Retrospective Study of an Airway Response System in a Pediatric Hospital

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Impact of Type 2 Diabetes Mellitus on Survival in Head and Neck Squamous Cell Carcinoma

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Hearing Outcomes after Ossicular Reconstruction with Removal of the Malleus

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Health-related quality of life and influencing factors among migrant children in Shaoxing, China

Due to increasing export of labor service, many children following their parents leave from rural areas to urban areas in China. These migrant children might have psychological stress and lower quality of life...

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Development and use of a content search strategy for retrieving studies on patients' views and preferences

Identifying scientific literature addressing patients' views and preferences is complex due to the wide range of studies that can be informative and the poor indexing of this evidence. Given the lack of guidan...

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Health-related quality of life of HIV infected adults with and without Visceral Leishmaniasis in Northwest Ethiopia

Health-related quality of life (HRQoL) is an important outcome measure among HIV infected patients receiving antiretroviral therapy (ART). When HIV infected patients coinfected with Visceral Leishmaniasis (VL)...

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Health-related quality of life in pregnant women living with HIV: a comparison of EQ-5D and SF-12

This paper investigates the properties and performance of the two generic measures, EQ-5D and SF-12, for Health-Related Quality of Life (HRQoL) assessments of pregnant women living with HIV in Kunming City, Yi...

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Effect of personality traits on adherence with positive airway pressure therapy in obstructive sleep apnea patients

Abstract

Purpose

Patient adherence with positive airway pressure (PAP) therapy is a significant clinical problem in obstructive sleep apnea treatment. Personality traits may be a factor for non-adherence. The aim of this study is to investigate the relationship between PAP therapy adherence and patient personality traits.

Methods

Patients were screened and recruited during their visit to a sleep clinic. Baseline data were collected from each patient's electronic chart. Behavioral inhibition system/behavioral activation system (BIS/BAS) scales, short measure of five-factor model personality traits (mini-IPIP), positive and negative affect score (PANAS), and appetitive motivation scores (AMS) tests were used to measure personality traits. Data from the PAP device were obtained following a minimum of an initial 30 days, with adherence defined as >4 h/night on 70% of nights. Univariate and multivariate logistic regression and Pearson correlation tests were used to analyze the data.

Results

A total of 400 patients were recruited. Three hundred twenty-one patients had all the data and were included in the study. Behavioral activation system–fun seeking (BAS-FS) and, to a certain extent, negative affect were significantly associated with adherence. Intellect/imagination was marginally significant. Additionally, older age (>65 years), profession, PAP type, side effects, efficiency, apnea–hypopnea index (AHI), and residual AHI showed significant associations with patient adherence with PAP therapy. Multivariate analysis revealed that BAS-FS was still a significant predictor of adherence even after adjusting for other covariates.

Conclusion

BAS-FS, negative affect, and intellect/imagination are significant factors for adherence to PAP therapy in obstructive sleep apnea patients.

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Evaluation of Contamination Risks with Coxsackievirus B4 E2 in Swiss Albino Mice Stools

Abstract

Coxsackie B4 (CV-B4), is a major cause of viral myocarditis, dilated cardiomyopathy, and pancreatitis. Like other human enteroviruses, CV-B4 is ubiquitous, excreted in the stool, transmitted by fecal–oral route, and persists in the environment. In the context of studies on CV-B4 infection, it is important to investigate how this virus can be eliminated and to show the possibility of contamination risk with a CV-B4 E2 infected Swiss albino mice. Swiss albino female mice were inoculated with CV-B4 E2 strain and divided in two groups: the first was intraperitoneally (I.P.) infected; the second was orally infected. In order to study the CV-B4 E2 infection in mice, total RNA was extracted from thymus, spleen, pancreas, and intestine, and viral genome was detected using semi-nested (RT-PCR). To further demonstrate infection or immunization of mice, Sera obtained from infected mice were assayed in vitro for their neutralizing antibody. To detect virus in stool of infected mice, stool samples were collected at different post-infection (p.i.) times. Neutralizing antibodies were detectable all along the follow-up period (Day 0, 1, 3, 7, 9, 17, 22, 30, 45, 60 p.i.) in I.P and oral infected mice. Our results showed that when mice were inoculated successively at day 0 and day 8, neutralizing activity was increased in I.P route more than in the oral route. Viral isolation in HEp-2 cells showed negative results. Stool viral analyses reveal a low detection of the CV-B4 E2 genome for all infected mice. In conclusion, our experiments demonstrated that there are no risks linked with the stool of CV-B4 E2 of Swiss albino mice. It would be interesting to characterize the inhibitors of the virus infectivity in these biological samples (stool) and investigate their targets and mechanisms of action.

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Editorial Board

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'My mouth ulcer turned out to be head and neck cancer but I'm determined to give others hope' - Bournemouth Echo

Bournemouth Echo

'My mouth ulcer turned out to be head and neck cancer but I'm determined to give others hope' Bournemouth Echo A SELFLESS woman who was diagnosed with head and neck cancer when a mouth ulcer would not go away is determined her battle will help others. Marie Campbell, known as Ali, is urging people to 'sponsor' her through six weeks of radiotherapy and will ... and more »

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Coblation Versus Conventional Tonsillectomy: A Double Blind Randomized Controlled Trial

Abstract

Post tonsillectomy bleeding and pain are two main problems following traditional tonsillectomy. Coblation therapy (controlled ablation) was first used in tonsillectomy in 2001. A great amount of literature debated around its use with controversial opinions regarding its benefits, efficacy, and cost. This is a prospective double-blind randomized controlled study that compares between coblation tonsillectomy and conventional tonsillectomy as regard operative time, operative blood loss, time needed to return back to the normal activity and diet, and incidence of postoperative hemorrhage whether primary or secondary. The study included 1004 patients with mean age of 10.4 years (range from 4 to 35 years). The first group (coblation tonsillectomy group) included 507 patients, age ranging from 4 to 35 years with mean age 15.1 year. This group included 277 female (54.6%) and 230 male (45.4%). The second group (conventional tonsillectomy group) included 497 patients, age ranging from 4 to 24 years and mean age 14.7 years. This group included 274 female (55.1%) and 223 male (44.9%). Coblation tonsillectomy offers significant advantages over dissection method with less operative time, decreased intraoperative blood loss, early restoration of daily activities and normal diet. However coblation tonsillectomy is associated with a higher incidence of secondary hemorrhage.

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Testicular cancer specialist in waukesha - Does cialis work for everyone - Forward Florida

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Hypogonadal Men with Higher Body Mass Index have Higher Bone Density and Better Bone Quality but Reduced Muscle Density

Abstract

Although hypogonadism is a risk factor for bone loss and fractures, the different etiopathophysiology and hormonal profile of classical and obesity-induced hypogonadism may lead to differences in musculoskeletal profile. This is a cross-sectional study of hypogonadal men between 40 and 74 years old. Our outcomes include: areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry; volumetric BMD (vBMD) and soft tissue composition of the tibia by peripheral quantitative computed tomography. Fracture risk assessment tool (FRAX) scores were evaluated. Testosterone, estradiol, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin, C-telopeptide, osteocalcin, and sclerostin were measured. We divided the population into subgroups of BMI: group 1: BMI < 30; group 2: BMI ≥30 to <35 and group 3: BMI ≥ 35 kg/m². One-hundred five men were enrolled. Spine and hip aBMD, and total and trabecular vBMD at the 4% tibia significantly increased with increasing BMI. Cortical thickness (330.7 ± 53.2, 343.3 ± 35.4, and 358.7 ± 38.2 mm, p = 0.04; groups 1, 2 and 3, respectively) and cortical area (5.3 ± 0.7, 5.5 ± 0.6, and 5.7 ± 0.6 mm, p = 0.01; groups 1, 2 and 3, respectively) at 38% tibia increased with increasing BMI. While absolute lean mass increased with increasing BMI, % lean mass and muscle density (70.2 ± 5.0, 71.3 ± 6.4, and 67.1 ± 5.1 mg/cm³; groups 1, 2 and 3, respectively) were lowest in group 3. Although severely obese hypogondal men have better BMD and bone quality, they have reduced muscle density, the significance of which remains to be determined.

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Safety of Antiplatelet Agents: Analysis of ‘Real-World’ Data from the Italian National Pharmacovigilance Network

Abstract

Introduction

According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs).

Methods

Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class.

Results

Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of 'life-threatening' events and 'death'.

Conclusions

Based on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice.

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Validation of an Algorithm for Semi-automated Estimation of Voice Relative Fundamental Frequency

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Book Review: Differential Diagnosis in Neuroimaging: Head and Neck

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Distinct preoperative clinical features predict four histopathological subtypes of high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum

The Cancer Genome Atlas Research Network reported that high-grade serous carcinoma (HGSC) can be classified based on gene expression profiles into four subtypes, termed "immunoreactive," "differentiated," "pro...

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Cancer incidence in eastern Morocco: cancer patterns and incidence trends, 2005–2012

Cancer is one of the major health problems worldwide. In this article, we present for the first time the cancer incidence trends, the distribution and the socioeconomic profile of incident cancer cases in East...

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Adherence and feasibility of 2 treatment schedules of S-1 as adjuvant chemotherapy for patients with completely resected advanced lung cancer: a multicenter randomized controlled trial

We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients.

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Rare triad of periampullary carcinoid, duodenal gastrointestinal stromal tumor and plexiform neurofibroma at hepatic hilum in neurofibromatosis type 1: a case report

Neurofibromatosis type 1 is a relatively common inherited disorder. Patients with neurofibromatosis type 1 are at high risk of developing neurogenic, neuroendocrine and mesenchymal intra-abdominal tumors. Alth...

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MicroRNA-222 influences migration and invasion through MIA3 in colorectal cancer

miR-222 has been reported to be overexpressed in colorectal cancer and it influences cancer cell proliferation, drug resistance and metastasis. However, the underlying molecular mechanism of miR-222 in colorec...

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Treatment of cutaneous iatrogenic Kaposi sarcoma with topical timolol

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Issue Information - JEB

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Neutrophilic dermatosis of hands preceding extensive small cell lung cancer

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Periprocedural Oxygenation of Obese Obstructive Sleep Apnea Patients In and Out of the Operating Room - Anesthesiology News

Periprocedural Oxygenation of Obese Obstructive Sleep Apnea Patients In and Out of the Operating Room Anesthesiology News ... by 2020, with many countries not far behind.1 It is associated with an increased risk for comorbidities including diabetes, hypertension, dyslipidemia, stroke, heart disease, and several forms of cancer.1 This necessitates mounting medical ...

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PIM-1 mRNA expression is a potential prognostic biomarker in acute myeloid leukemia

High expression of proviral integration site for Moloney murine leukemia virus-1 (PIM-1), a serine/threonine kinase, is associated with many cancers. The main purpose of this study were to investigate that the...

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Molecular targeting in acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogenous disease associated with distinct genetic and molecular abnormalities. Somatic mutations result in dysregulation of intracellular signaling pathways, epigenetics, ...

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In silico prediction of novel therapeutic targets using gene–disease association data

Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the ...

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Vaccine-draining lymph nodes of cancer patients for generating anti-cancer antibodies

Our research is focused on using the vaccine draining lymph node to better understand the immune response to cancer vaccines and as a possible source of anti-cancer reagents. We evaluated vaccine draining lymp...

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Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases. Methylprednisolone (MP) is a common drug against inflammation in clinic. In this study, we aim to i...

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Medullary Thyroid Cancer Drug Market: Supply, Demand, Prices, Trading, Competition Analysis Research Report - Medgadget (blog)

Medullary Thyroid Cancer Drug Market: Supply, Demand, Prices, Trading, Competition Analysis Research Report Medgadget (blog) The 'Global Medullary Thyroid Cancer Drug Industry, 2012-2022 Market Research Report' is a professional and in-depth study on the current state of the global Medullary Thyroid Cancer Drug industry with a focus on the Chinese market. The report provides ...

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Retraction Statement: Role of α7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation

Retraction: Paleari L, Catassi A, Ciarlo M, Cavalieri Z, Bruzzo C, Servent D, Cesario A, Chessa L, Cilli M, Piccardi F, Granone P, Russo P. Role of α7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation. Cell Prolif. 2008;41:936-959. http://ift.tt/2wh7QfZ

The above article from Cell Proliferation, published online on 18 November 2008 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 41, pp. 936-959, has been retracted by agreement between the Editor in Chief, Dr Catherine Sarraf, and John Wiley and Sons Ltd. The retraction has been agreed upon following the recent confirmation regarding an internal investigation that was conducted by the Institutional Office for Research Integrity (UIR) at the National Institute for Cancer Research, Genova, Italy, in 2009, which found evidence of fabricated/duplicated data within the article.

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'My mouth ulcer turned out to be head and neck cancer but I'm determined to give others hope' - Bournemouth Echo

Bournemouth Echo

'My mouth ulcer turned out to be head and neck cancer but I'm determined to give others hope' Bournemouth Echo A SELFLESS woman who was diagnosed with head and neck cancer when a mouth ulcer would not go away is determined her battle will help others. Marie Campbell, known as Ali, is urging people to 'sponsor' her through six weeks of radiotherapy and will ... and more »

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The cell envelope-associated phospholipid-binding protein LmeA is required for mannan polymerization in mycobacteria [Microbiology]

The integrity of the distinguishing, multilaminate cell envelope surrounding mycobacteria is critical to its survival and pathogenesis. The prevalence of phosphatidylinositol mannosides in the cell envelope suggests an important role in the mycobacterial life cycle. Indeed, deletion of the pimE gene (ΔpimE) encoding the first committed step in phosphatidylinositol hexamannoside biosynthesis in Mycobacterium smegmatis results in the formation of smaller colonies than wildtype colonies on Middlebrook 7H10 agar. To further investigate potential contributors to cell-envelope mannan biosynthesis while taking advantage of this colony morphology defect, we isolated spontaneous suppressor mutants of ΔpimE that reverted to wildtype colony size. Of 22 suppressor mutants, 6 accumulated significantly shorter lipomannan or lipoarabinomannan. Genome sequencing of these mutants revealed mutations in genes involved in the lipomannan/lipoarabinomannan biosynthesis, such as those encoding the arabinosyltransferase EmbC and the mannosyltransferase MptA. Furthermore, we identified three mutants carrying a mutation in a previously uncharacterized gene, MSMEG_5785, that we designated lmeA. Complementation of these suppressor mutants with lmeA restored the original ΔpimE phenotypes, and deletion of lmeA in wildtype M. smegmatis resulted in smaller lipomannan as observed in the suppressor mutants. LmeA carries a predicted N-terminal signal peptide, and density gradient fractionation and detergent extractability experiments indicated that LmeA localizes to the cell envelope. Using a lipid ELISA assay, we found that LmeA binds to plasma membrane phospholipids such as phosphatidylethanolamine and phosphatidylinositol. LmeA is widespread throughout the Corynebacteriales; therefore, we concluded that LmeA is an evolutionarily conserved cell-envelope protein critical for controlling the mannan chain length of lipomannan/lipoarabinomannan.

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Tobacco-specific carcinogens induce hypermethylation, DNA adducts and DNA damage in Bladder Cancer

Smoking is a major risk factor for the development of Bladder Cancer (BLCA); however, the functional consequences of the carcinogens in tobacco smoke and BLCA-associated metabolic alterations remains poorly defined. We assessed the metabolic profiles in BLCA smokers and non-smokers, and identified the key alterations in their metabolism. Liquid Chromatography - Mass Spectrometry (LC-MS), and bioinformatic analysis were performed to determine the metabolome associated with BLCA smokers and were further validated in cell line models. Smokers with BLCA were found to have elevated levels of methylated metabolites, polycyclic aromatic hydrocarbons (PAHs), DNA adducts and DNA damage. DNA methyltransferase 1 (DNMT1) expression was significantly higher in smokers than non-smokers with BLCA. An integromics approach, using multiple patient cohorts, revealed strong associations between smokers and high-grade BLCA. In vitro exposure to the tobacco smoke carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) led to increase in levels of methylated metabolites, DNA adducts, and extensive DNA damage in BLCA cells. Co-treatment of BLCA cells with these carcinogens and the methylation inhibitor 5-aza-2'-deoxycytidine (AZA) rewired the methylated metabolites, DNA adducts, DNA damage. These findings were confirmed through the isotopic labeled metabolic flux analysis. Screens using smoke associated metabolites and DNA adducts could provide robust biomarkers and improve individual risk prediction in BLCA smokers. Non-invasive predictive biomarkers that can stratify the risk of developing BLCA in smokers could aid in early detection and treatment.

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The Second Generation PGI2 Analogue Treprostinil Fails to Chemoprevent Tumors in a Murine Lung Adenocarcinoma Model

Prostacyclin (prostaglandin I2, PGI2) over-production in FVB/N mice prevents the formation of carcinogen and tobacco smoke induced adenomas, and administration of the oral prostacyclin analog iloprost to wild type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared to placebo. Next generation oral prostacyclin analogues, like treprostinil, were developed for treatment of pulmonary arterial hypertension (PAH). Based on our prior studies with iloprost, we performed preclinical studies examining the ability of treprostinil to chemoprevent urethane-induced murine lung adenocarcinoma. We determined the maximum tolerated dose in chow (prior studies delivered treprostinil by gavage), and this dose produced serum levels in experimental animals similar to those found in PAH patients treated with treprostinil. We then examined the chemopreventive efficacy of treprostinil exposure initiated both before (1 week) and after (6 weeks) urethane exposure to better model chemoprevention studies conducted in former smokers. Neither of these dosing strategies prevented murine lung cancer; however, we did detect changes in pulmonary inflammatory cell infiltrate and expression of CXCR4 (a chemokine receptor previously shown to increase in response to treprostinil exposure) in tumor-bearing, treprostinil-treated animals, indicating that the drug was bioavailable. One potential explanation stems from iloprost and treprostinil differentially activating cell surface prostaglandin receptors and intracellular peroxisome proliferator-activated receptors. When murine lung tumor cells were treated with treprostinil, their proliferation rate increased; in contrast, iloprost had no effect on proliferation. Future investigations comparing these two agents will provide insight into the chemopreventive mechanisms of iloprost.

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Phosphoproteomic analysis reveals the importance of kinase regulation during orbivirus infection [Research]

Bluetongue virus (BTV) causes infections in wild and domesticated ruminants with high morbidity and mortality and is responsible for significant economic losses in both developing and developed countries. BTV serves as a model for the study of other members of the Orbivirus genus. Previously, the importance of casein kinase 2 for BTV replication was demonstrated. To identify intracellular signalling pathways and novel host-cell kinases involved during BTV infection, the phosphoproteome of BTV infected cells was analysed. Over 1000 phosphosites were identified using mass spectrometry, which were then used to determine the corresponding kinases involved during BTV infection. This analysis yielded protein kinase A (PKA) as a novel kinase activated during BTV infection. Subsequently, the importance of PKA for BTV infection was validated using a PKA inhibitor and activator. Our data confirmed that PKA was essential for efficient viral growth. Further, we showed that PKA is also required for infection of equid cells by African horse sickness virus, another member of the Orbivirus genus. Thus, despite their preference in specific host species, orbiviruses may utilize the same host signaling pathways during their replication.

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Furosine induces DNA damage and cell death in selected human cell lines: a strong toxicant to kidney Hek-293 cells

Abstract

Ne-(2-furoylmethyl)-l-lysine (furosine) is well-known indicator of early stage of Maillard reaction in processed food. Yet the toxicological aspects associated with its exposure remain rarely studied. Here, we investigated the effects of furosine exposure on cell viability, DNA damage, and its mutagenic potential by using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide), TUNEL assay (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay), and Ames assay techniques on human cell lines, i.e., liver HepG-2, kidney Hek-293, neuronal SK-N-SH, and intestinal Caco-2, respectively. Our results showed that kidney Hek-293 cell line was the most sensitive to furosine exposure as significant reduction in cell viability and induction of DNA damage were observed at 50 mg/L concentration. In contrast, intestinal Caco-2 cell lines showed resistance to furosine exposure as DNA damage was only observed at 800 mg/L concentration of furosine. Ames assay indicated that furosine has no mutagenic effects on TA 100 and TA 1535 strains. Hence, this study suggests that furosine is a strong toxicant for kidney cells.

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The Effect of Metabolic and Bariatric Surgery on DNA Methylation Patterns

Abstract

Purpose of Review

Metabolic and bariatric surgery (MBS) is considered to be the most effective treatment for obesity. Not only due to the significant weight reduction but also because of the many health benefits associated with it. In the last 5 years, several studies have suggested that epigenetic modifications could be involved in the mechanisms underlying the response to bariatric surgery. In this review, we will compile the different studies (2012–2017) concerning the effect of this surgical procedure on DNA methylation patterns (the most studied epigenetic marker) and its association with metabolic improvement. This is an emerging area, and currently, there are not many studies in the literature. The aim is to show what has been done so far and what the future direction in this emerging area might be.

Recent Findings

Recent findings have shown how metabolic and bariatric surgery modifies the DNA methylation profile of the specific genes associated with the pathophysiology of the disease. The studies were performed in morbidly obese subjects, mainly in women, with the aim of reducing weight and improving the obesity-associated comorbidities. DNA methylation has been measured both in specific tissue and in peripheral blood samples. In general, studies about site-specific DNA methylation have shown a change in the methylation profile after surgery, whereas the studies analyzing global DNA methylation are not so conclusive.

Summary

Summing up, metabolic and bariatric surgery can modify the DNA methylation profile of different genes and contributes to the metabolic health benefits that are often seen after metabolic and bariatric surgery. Although there are still many issues to be resolved, the capacity to revert the DNA methylation profile of specific sites opens a window for searching for target markers to treat obesity-related comorbidities.

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IJMS, Vol. 18, Pages 1863: SMAD2 Inactivation Inhibits CLDN6 Methylation to Suppress Migration and Invasion of Breast Cancer Cells

IJMS, Vol. 18, Pages 1863: SMAD2 Inactivation Inhibits CLDN6 Methylation to Suppress Migration and Invasion of Breast Cancer Cells

International Journal of Molecular Sciences doi: 10.3390/ijms18091863

Authors: Yan Lu Liping Wang Hairi Li Yanru Li Yang Ruan Dongjing Lin Minlan Yang Xiangshu Jin Yantong Guo Xiaoli Zhang Chengshi Quan

The downregulation of tight junction protein CLDN6 promotes breast cancer cell migration and invasion; however, the exact mechanism underlying CLDN6 downregulation remains unclear. CLDN6 silence is associated with DNA methyltransferase 1 (DNMT1) mediated DNA methylation, and DNMT1 is regulated by the transforming growth factor beta (TGFβ)/SMAD pathway. Therefore, we hypothesized that TGFβ/SMAD pathway, specifically SMAD2, may play a critical role for CLDN6 downregulation through DNA methyltransferase 1 (DNMT1) mediated DNA methylation. To test this hypothesis, we blocked the SMAD2 pathway with SB431542 in two human breast cancer cell lines (MCF-7 and SKBR-3). Our results showed that treatment with SB431542 led to a decrease of DNMT1 expression and the binding activity for CLDN6 promoter. The methylation level of CLDN6 promoter was decreased, and simultaneously CLDN6 protein expression increased. Upregulation of CLDN6 inhibited epithelial to mesenchymal transition (EMT) and reduced the migration and invasion ability of both MCF-7 and SKBR-3 cells. Furthermore, knocked down of CLDN6 abolished SB431542 effects on suppression of EMT associated gene expression and inhibition of migration and invasion. Thus, we demonstrated that the downregulation of CLDN6 is regulated through promoter methylation by DNMT1, which depends on the SMAD2 pathway, and that CLDN6 is a key regulator in the SMAD2/DNMT1/CLDN6 pathway to inhibit EMT, migration and invasion of breast cancer cells.

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Early severe anemia as the first sign of cystic fibrosis

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Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies

Summary

Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD). Blood samples for alisertib and 2 major metabolites were collected up to 72 h (Study 1) and 96 h (Study 2) postdose. Area under the curve from time zero extrapolated to infinity (AUC_0-inf) and maximum concentrations (C_max) were calculated and compared using analysis of variance to estimate least squares (LS) mean ratios and 90% confidence intervals (CIs). Results The LS mean ratios (90% CIs) for alisertib AUC_0-inf and C_max in the presence compared to the absence of esomeprazole were 1.28 (1.07, 1.53) and 1.14 (0.97, 1.35), respectively. The LS mean ratios (90% CIs) for alisertib AUC_0-inf and C_max in the presence compared to the absence of rifampin were 0.53 (0.41, 0.70) and 1.03 (0.84, 1.26), respectively. The LS mean ratios (90% CIs) for alisertib AUC_0-inf and C_max in the presence compared to the absence of itraconazole were 1.39 (0.99, 1.95) and 0.98 (0.82, 1.19), respectively. Conclusions The use of gastric acid reducing agents, strong CYP3A inhibitors or strong metabolic enzyme inducers should be avoided in patients receiving alisertib.

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Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline ... - Markets Insider

Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline ... Markets Insider ... Head And Neck Cancer Squamous Cell Carcinoma, Refractory Multiple Myeloma, Relapsed Multiple Myeloma, Rhabdomyosarcoma, Salivary Gland Cancer, Skin Cancer, Soft Tissue Sarcoma, Ureter Cancer, Urethral Cancer and Urinary Tract Cancer. and more »

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Cesarean sections in a secondary level care hospital of Cameroon: an analysis of their six-year trends and adverse neonatal outcomes

The objectives of this study were to determine the trends of CS in a regional hospital in Cameroon and to explore its association with adverse neonatal outcomes.

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Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials

Infectivity trials and toxicity testing in rodents are important prerequisites to the use of compounds in man. However, trials in rats and mice are expensive and there are ethical considerations. Galleria mellone...

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In vitro and in vivo imaging and tracking of intestinal organoids from human-induced pluripotent stem cells [Research]

Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human-induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters (KLF5^mCherry and ISX^eGFP). Then hIOs were efficiently induced from those transgenic hiPSC lines in which monomeric Cherry– or enhanced green fluorescent protein–expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.—Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human-induced pluripotent stem cells.

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Telomere length dynamics in early life: the blood-and-muscle model [Research]

Telomere length (TL) trajectories in somatic tissues during human growth and development are poorly understood. We examined a blood-and-muscle model during early life, focusing on TL trajectories in leukocytes, representing the highly proliferative hematopoietic system, and skeletal muscle, a minimally proliferative tissue. Leukocyte TL (LTL) and skeletal muscle TL (MTL) were measured in 28 fetuses and 73 children. LTL and MTL were highly variable across individuals (sd: fetal LTL = 0.72 kb, MTL = 0.72 kb; children LTL = 0.81 kb, MTL = 0.82 kb) but were highly correlated within individuals (fetuses, r = 0.76, P < 0.0001; children, r = 0.87, P < 0.0001). LTL was shorter than MTL in fetuses (10.63 vs. 11.01 kb; P = 0.0004) and children (8.46 vs. 9.40 kb; <0.0001). The LTL-MTL gap was smaller in fetuses than children. TL in children was inversely correlated with body mass index (BMI) (LTL: –0.047 ± 0.016 kb/BMI, P < 0.005; MTL: –0.037 ± 0.017 kb/BMI, P = 0.03). We conclude that variations in TL across adults and differences in TL between somatic tissues are largely established in early life. Because TL plays a significant role in aging-related diseases, insight into the factors that fashion TL in somatic tissues during early development should contribute to an understanding of the relationship of TL with these disease and longevity in humans.—Sabharwal, S., Verhulst, S., Guirguis, G., Kark, J. D., Labat, C., Roche, N. E., Martimucci, K., Patel, K., Heller, D. S., Kimura, M., Chuang, D., Chuang, A., Benetos, A., Aviv, A. Telomere length dynamics in early life: the blood-and-muscle model.

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Experimental confirmation of the C3 tickover hypothesis by studies with an Ab (S77) that inhibits tickover in whole serum [Research]

The complement component 3 (C3) tickover hypothesis was put forward in the early 1970s to account for the spontaneous activation of the alternative complement pathway that occurs after the genetic absence or in vitro depletion of Factor I, the enzyme that is essential for the breakdown of C3b. The hypothesis was widely accepted, but experimental demonstration of the tickover was elusive. A phage Ab against C3b that inhibited the alternative complement pathway, but not the classical pathway, was described in 2009. Studies using this Ab in a variety of assays have now demonstrated that it acts primarily by inhibiting tickover, thereby confirming that tickover really exists.—Lachmann, P. J., Lay, E., Seilly, D. J. Experimental confirmation of the C3 tickover hypothesis by studies with an Ab (S77) that inhibits tickover in whole serum.

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Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll-like receptor 4 [Research]

Acute lung injury (ALI) is a common cause of morbidity in patients after severe injury due to dysregulated inflammation, which is believed to be driven by gut-derived inflammatory mediators carried via mesenteric lymph (ML). We have previously demonstrated that nano-sized extracellular vesicles, called exosomes, secreted into ML after trauma/hemorrhagic shock (T/HS) have the potential to activate immune cells in vitro. Here, we assess the function of ML exosomes in the development of T/HS-induced ALI and the role of TLR4 in the ML exosome–mediated inflammatory response. ML exosomes isolated from rats subjected to T/HS stimulated NF-B activation and caused proinflammatory cytokine production in alveolar macrophages. In vivo experiments revealed that intravenous injection of exosomes harvested after T/HS, but not before shock, caused recruitment of inflammatory cells in the lung, increased vascular permeability, and induced histologic ALI in naive mice. The exosome-depleted supernatant of ML had no effect on in vitro and in vivo inflammatory responses. We also demonstrated that both pharmacologic inhibition and genetic knockout of TLR4 completely abolished ML exosome–induced cytokine production in macrophages. Thus, our findings define the critical role of exosomes secreted into ML as a critical mediator of T/HS-induced ALI through macrophage TLR4 activation.—Kojima, M., Gimenes-Junior, J. A., Chan, T. W., Eliceiri, B. P., Baird, A., Costantini, T. W., Coimbra, R. Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll-like receptor 4.

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Involvement of Semaphorin (Sema4D) in T-Dependent Activation of B Cells

The involvement of endogenous semaphorin (Sema4D) into the key stage of T-dependent differentiation of B cells, formation of plasmoblasts, was demonstrated in vitro in T/B cell co-culture under conditions of polyclonal activation of T cells. The effect of semaphorin was not associated with activation of high-affinity Sema4D receptor plexin B1, but involves lowaffinity receptor CD72. These data indicate that Sema4D-dependent signal regulates not only the initial stage of B-cell activation, proliferative response to the antigen, but also further differentiation of B cells into plasma cells.

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Activation of Microglyocytes in the Anterior Horns of Rat Spinal Cord after Administration of Bacterial Lipopolysaccharide

We studied the reaction of the microglia of the anterior horns of the rat spinal cord to intraperitoneal administration of bacterial LPS. Immunohistochemical analysis showed that acute systemic inflammation leads to activation of more than half of microglial cells as soon as in 24 h after LPS injection, while the total number of microglial cells does not change significantly. It was hypothesized that activated microglial cells are involved in the reorganization of synaptic connections, but do not have a neurotoxic effect.

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Effects of Miramistin and Phosprenil on Microbial Biofilms

Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 μg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 μg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.

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The level of Hydrogen Peroxide in HeLa Cells in an Ozonated Medium

We studied the role of hydrogen peroxide in the response of tumor cells to treatment with ozonated culture medium. Changes of the level of hydrogen peroxide in tumor cells incubated in ozonated medium were detected by using fluorescence microscopy and genetically-encoded sensor HyPer2. Modifications of fluorescent properties of the sensor reflecting accumulation of hydrogen peroxide in the cell cytoplasm were detected within 70 min from the start of exposure. The concentration of hydrogen peroxide continued to increase until 375 min. The revealed changes support the involvement of hydrogen peroxide in the cell response to ozone treatment.

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Human Umbilical Cord Mesenchymal Stromal Cells Support Viability of Umbilical Cord Blood Hematopoietic Stem Cells but not the “Stemness” of Their Progeny in Co-Culture

Cell—cell interactions and the ability of mesenchymal stromal cells to support the expansion of hematopoietic progenitor cells were studied in co-culture of human umbilical cord tissue-derived mesenchymal stromal cells and nucleated umbilical cord blood cells. It was found that hematopoietic stem cells from the umbilical cord blood are capable to adhere to mesenchymal stromal cells and proliferate during 3-4 weeks in co-culture. However, despite the formation of hematopoietic foci and accumulation of CD34⁺ and CD133⁺ cells in the adherent cell fraction, the ability of newly generated blood cells to form colonies in semi-solid culture medium was appreciably reduced. These findings suggest that human umbilical cord tissue-derived mesenchymal stromal cells display a weak capability to support the "stemness" of hematopoietic stem cell progeny despite long-term maintenance of their viability and proliferation.

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Effect of Pectin Gel Particles on Endotoxemia Induced by Restraint Stress in Mice

We studied the effect of pectin gel particles on endotoxemia in mice induced by restraint stress. It was shown that the concentration of LPS in mouse blood increased during restraint stress, which was associated with memory impairment. Pectin gel particles prevented the development of stress-induced endotoxemia and memory impairment in mice.

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Immunohistochemical Parameters of Musashi-1 in Nodular and Diffuse Adenomyosis

Comparative immunohistochemical analysis of the expression of somatic stem cells marker Musashi-1 in the endometrium was performed during various phases of menstrual cycle and in patients with nodular and diffuse adenomyosis. The expression of Musashi-1 reflecting proliferative potential of epithelial and stromal cells was quantitatively analyzed by the optical density in the nuclei and cytoplasm of epithelial and stromal cells of the eutopic endometrium and adenomyosis foci. In the eutopic endometrium, the immunohistochemical reaction was more intensive during proliferation phase in comparison with secretion phase. Enhanced expression of Musashi-1 was observed in adenomyosis foci in comparison with endometrial cells. The most intensive staining was found in nodular adenomyosis, especially in epithelial cells during the secretion phase. These data attest to the role of somatic stem cells in the development and progression of various forms of adenomyosis.

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Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

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Role of JAK1, JAK2, and JAK3 in Functional Stimulation of Mesenchymal Precursor Cells by Alkaloid Songorine

We studied the role of some JAK in the effect of diterpene alkaloid songorine on realization of the growth potential of mesenchymal precursor cells. The participation of JAK1, JAK2, and JAK3 in stimulation of proliferation of the precursor cells was demonstrated. Specific inhibitors of these JAK reduced the yield of fibroblast CFU and the rate of their division. Inhibition of JAK2 against the background of songorine treatment increased the rate of precursor differentiation.

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Selective Cytotoxicity of Manganese Nanoparticles against Human Glioblastoma Cells

Toxicity of different types of manganese nanoparticles against glioblastoma U-87MG and U-251 cells and normal human cells was studied using MTT test. The selectivity of the toxic effect of nanoparticles was evaluated as the ratio of 50% cytotoxic concentration (СС₅₀) for human embryos fibroblasts (FECh-15) to their СС₅₀ for tumor cells. Five of 6 samples of tested nanoparticles demonstrated selective toxic effect in vitro. Manganese oxide nanoparticles were characterized by maximum selectivity (СС₅₀ 6.9 nM and 2.1 nM for U-87MG and U-251 cells, respectively): selectivity index for glioblastoma U-87MG and U-251 cells was 29 and 95.2, respectively. Manganese oxide nanoparticles used for MRI detection of gliomas can be used for designing an oncolytic agent for the treatment of glial tumors in humans.

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The Influence of Proinflammatory Factors on the Neuroprotective Efficiency of Multipotent Mesenchymal Stromal Cells in Traumatic Brain Injury

We studied the neuroprotective potential of multipotent mesenchymal stromal cells in traumatic brain injury and the effect of inflammatory preconditioning on neuroprotective properties of stem cells under in vitro conditions. To this end, the effects of cell incubation with LPS or their co-culturing with leukocytes on production of cytokines IL-1α, IL-6, TNFα, and MMP-2 and MMP-9 by these cells were evaluated. Culturing under conditions simulating inflammation increased the production of all these factors by multipotent mesenchymal stromal cells. However, acquisition of the inflammatory phenotype by stromal cells did not reduce their therapeutic effectiveness in traumatic brain injury. Moreover, in some variants of inflammatory preconditioning, multipotent mesenchymal stromal cells exhibited more pronounced neuroprotective properties reducing the volume of brain lesion and promoting recovery of neurological functions after traumatic brain injury.

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Changes in the Activity of Proteasomes and Calpains in Metastases of Human Lung Cancer and Breast Cancer

In patients with breast cancer and lung cancer, chymotrypsin-like and caspase-like activities of proteasomes and total activity of calpains in the primary tumor nodes and lymphogenic metastasis are elevated in comparison with the corresponding normal tissues. The development of lymphogenic metastases of breast cancer and lung cancer was associated with opposite change in caspase-like activity of proteasomes. These results can be useful for the development of methods for evaluation of aggressiveness of breast and lung cancer.

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Plasma Level of hsa-miR-619-5p microRNA Is Associated with Prostatic Cancer Dissemination beyond the Capsule

Profiles of circulating microRNA in the plasma of patients with prostate cancer with pathomorphological stages pT2, pT3, and pT4 are analyzed. The level of circulating microRNA hsa-miR-619-5p is elevated in patients with extracapsular spreading of the tumor, increasing significantly from stage pT2 to stage pT4.

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Application of Tetrameric Recombinant Human Butyrylcholinesterase as a Biopharmaceutical for Amelioration of Symptoms of Acute Organophosphate Poisoning

We present a procedure for optimizing the expression of recombinant tetrameric butyrylcholinesterase that enables large-scale production with the yield >30 mg/liter (>90 mg/roller bottle). Intravenous injection of the preparation significantly increased survival and decreased the severity of symptoms of poisoning with paraoxon, an organophosphorus toxin.

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Complete remission of brain metastasis of difficult-to-treat tumor ... - Science Daily

Science Daily

Complete remission of brain metastasis of difficult-to-treat tumor ... Science Daily Medical researchers report a remarkable treatment response in a patient participating in a clinical trial of a novel immune-system-based cancer therapy. and more »

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PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Meimei Zhao, Rui Geng, Xiang Guo, Ruoshi Yuan, Xiao Zhou, Yanyan Zhong, Yanfei Huo, Mei Zhou, Qinjian Shen, Yinglu Li, Weiguo Zhu, Jiadong Wang
The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

Graphical abstract

Teaser

RPA complex is a central player in multiple DNA repair pathways. Zhao et al. show that PCAF/GCN5-mediated acetylation of RPA1 is crucial for NER repair by promoting stable RPA1/XPA complex.


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UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Hanqing He, Jiajia Wang, Ting Liu
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltransferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation. Mutation of the acetylation site of RPA1 specifically impairs the ability of the protein to interact with the key nucleotide excision repair (NER) protein XPA, reduces XPA retention at sites of DNA damage caused by UV, compromises NER, and renders the cell hypersensitive to UV irradiation. Our data suggest that the acetylation status of RPA1 played a crucial role in repair of DNA damage via NER.

Graphical abstract

Teaser

He et al. find that the RPA1 protein becomes acetylated at lysine 163 in response to UV irradiation. Such acetylation specifically enhances interaction between RPA1 and the key NER protein XPA and promotes XPA retention at DNA damage sites. These findings suggest that RPA1 acetylation is a unique NER-related event.


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SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Ngat T. Tran, Michael T. Laub, Tung B.K. Le
The structural maintenance of chromosomes (SMC) complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using genome-wide methods and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome-partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Furthermore, we show that highly transcribed genes near parS that are oriented against SMC translocation disrupt arm alignment, suggesting that head-on transcription interferes with SMC translocation. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

Graphical abstract

Teaser

Tran et al. investigate the mechanism and function of SMC in the global organization of the Caulobacter chromosome. The findings suggest that SMC functions as a tether to actively cohese the chromosomal arms together and show that head-on transcription profoundly interferes with SMC translocation from the centromeric parS site.


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Feeling Stressed under the Sun? RPA1 Acetylation to the Rescue

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Debabrata Chakravarti, Tapas K. Hazra
Nucleotide excision repair (NER) requires replication protein A (RPA), among others, to respond to DNA damaging agents. In this issue of Cell Reports, He et al. (2017) and Zhao et al. (2017) show acetylation of RPA1 regulates the UV-induced DNA damage response.

Teaser

Nucleotide excision repair (NER) requires replication protein A (RPA), among others, to respond to DNA damaging agents. In this issue of Cell Reports, He et al. (2017) and Zhao et al. (2017) show acetylation of RPA1 regulates the UV-induced DNA damage response.


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Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Laina Freyer, Chih-Wei Hsu, Sonja Nowotschin, Andrea Pauli, Junji Ishida, Keiji Kuba, Akiyoshi Fukamizu, Alexander F. Schier, Pamela A. Hoodless, Mary E. Dickinson, Anna-Katerina Hadjantonakis
Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos. Transcriptomics at late gastrulation identified aberrant upregulation of erythroid and myeloid markers in mutant embryos prior to the appearance of physical malformations. Double-mutant analyses showed that loss of Apela signaling impacts early Aplnr-expressing mesodermal populations independently of the alternative ligand Apelin, leading to lethal cardiac defects in some Apela null embryos.

Graphical abstract

Teaser

Apela (a.k.a. Elabela, Ende, and Toddler) is a key signaling peptide that activates APLNR in mouse development. Freyer et al. show that lethal developmental defects in Apela mutants may rely on sufficient blood circulation. They suggest that extraembryonic mesoderm derivatives, including endothelial and hematopoietic progenitors, may be the first cell populations impacted by the loss of Apela.


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Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Yohei Shinmyo, Yukari Terashita, Tung Anh Dinh Duong, Toshihide Horiike, Muneo Kawasumi, Kazuyoshi Hosomichi, Atsushi Tajima, Hiroshi Kawasaki
Folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. However, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. By combining in utero electroporation and the CRISPR/Cas9 system, we succeeded in efficient gene knockout of Cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencephalic brains of ferrets. We show that Cdk5 knockout in the ferret cerebral cortex markedly impaired cortical folding. Furthermore, the results obtained from the introduction of dominant-negative Cdk5 into specific cortical layers suggest that Cdk5 function in upper-layer neurons is more important for cortical folding than that in lower-layer neurons. Cdk5 inhibition induced severe migration defects in cortical neurons. Taken together, our findings suggest that the appropriate positioning of upper-layer neurons is critical for cortical folding.

Graphical abstract

Teaser

Shinmyo et al. describe a highly efficient gene knockout method for the folded cerebral cortex of ferrets using the CRISPR/Cas9 system. Loss-of-function studies of the Cdk5 gene suggest that appropriate positioning of upper-layer neurons is crucial for cortical folding.


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Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Megan S. Wyeth, Kenneth A. Pelkey, Xiaoqing Yuan, Geoffrey Vargish, April D. Johnston, Steven Hunt, Calvin Fang, Daniel Abebe, Vivek Mahadevan, André Fisahn, Michael W. Salter, Roderick R. McInnes, Ramesh Chittajallu, Chris J. McBain
Although Netos are considered auxiliary subunits critical for kainate receptor (KAR) function, direct evidence for their regulation of native KARs is limited. Because Neto KAR regulation is GluK subunit/Neto isoform specific, such regulation must be determined in cell-type-specific contexts. We demonstrate Neto1/2 expression in somatostatin (SOM)-, cholecystokinin/cannabinoid receptor 1 (CCK/CB1)-, and parvalbumin (PV)-containing interneurons. KAR-mediated excitation of these interneurons is contingent upon Neto1 because kainate yields comparable effects in Neto2 knockouts and wild-types but fails to excite interneurons or recruit inhibition in Neto1 knockouts. In contrast, presynaptic KARs in CCK/CB1 interneurons are dually regulated by both Neto1 and Neto2. Neto association promotes tonic presynaptic KAR activation, dampening CCK/CB1 interneuron output, and loss of this brake in Neto mutants profoundly increases CCK/CB1 interneuron-mediated inhibition. Our results confirm that Neto1 regulates endogenous somatodendritic KARs in diverse interneurons and demonstrate Neto regulation of presynaptic KARs in mature inhibitory presynaptic terminals.

Graphical abstract

Teaser

Netos are considered critical kainate receptor (KAR) auxiliary subunits in glutamatergic principal cells, but their roles in GABAergic interneurons remain unexplored. Wyeth et al. find that somatodendritic KARs within diverse interneurons require Neto1, whereas both Neto1 and Neto2 regulate presynaptic KAR-mediated suppression of inhibitory transmission.


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The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Jui-Heng Tseng, Ling Xie, Sheng Song, Youmei Xie, Lauren Allen, Deepa Ajit, Jau-Shyong Hong, Xian Chen, Rick B. Meeker, Todd J. Cohen
The initiating events that promote tau mislocalization and pathology in Alzheimer's disease (AD) are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

Graphical abstract

Teaser

Tau mislocalization and aggregation are implicated in the pathogenesis of Alzheimer's disease. Tseng et al. report that endogenous neuronal tau re-localizes to distinct neuritic foci, which are active sites of calcium deregulation, leading to aberrant tau accumulation. These findings provide insights into the early-stage tau dysfunction that occurs in vulnerable neurons.


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Deletion of Nampt in Projection Neurons of Adult Mice Leads to Motor Dysfunction, Neurodegeneration, and Death

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Xiaowan Wang, Qiao Zhang, Ruisi Bao, Nannan Zhang, Yingzhen Wang, Luis Polo-Parada, Andrew Tarim, Aidan Alemifar, Xianlin Han, Heather M. Wilkins, Russell H. Swerdlow, Xinglong Wang, Shinghua Ding
Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) is the rate-limiting enzyme of the mammalian NAD⁺ biosynthesis salvage pathway. Using inducible and conditional knockout (cKO) mice, we show that Nampt gene deletion in adult projection neurons leads to a progressive loss of body weight, hypothermia, motor neuron (MN) degeneration, motor function deficits, paralysis, and death. Nampt deletion causes mitochondrial dysfunction, muscle fiber type conversion, and atrophy, as well as defective synaptic function at neuromuscular junctions (NMJs). When treated with nicotinamide mononucleotide (NMN), Nampt cKO mice exhibit reduced motor function deficits and prolonged lifespan. iNAMPT protein levels are significantly reduced in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, indicating the involvement of NAMPT in ALS pathology. Our findings reveal that neuronal NAMPT plays an essential role in mitochondrial bioenergetics, motor function, and survival. Our study suggests that the NAMPT-mediated NAD⁺ biosynthesis pathway is a potential therapeutic target for degenerative MN diseases.

Graphical abstract

Teaser

Wang et al. find that projection neuron NAMPT is essential for mitochondrial bioenergetics, motor function, and survival of adult mice and that iNAMPT is reduced in ALS patients. NMN improves health and extends the lifespan of Nampt knockout mice. Their findings suggest therapeutic avenues for motor neuron degenerative diseases.


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Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Theodoros I. Roumeliotis, Steven P. Williams, Emanuel Gonçalves, Clara Alsinet, Martin Del Castillo Velasco-Herrera, Nanne Aben, Fatemeh Zamanzad Ghavidel, Magali Michaut, Michael Schubert, Stacey Price, James C. Wright, Lu Yu, Mi Yang, Rodrigo Dienstmann, Justin Guinney, Pedro Beltrao, Alvis Brazma, Mercedes Pardo, Oliver Stegle, David J. Adams, Lodewyk Wessels, Julio Saez-Rodriguez, Ultan McDermott, Jyoti S. Choudhary
Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.

Graphical abstract

Teaser

Roumeliotis et al. use in-depth proteomics to assess the impact of genomic alterations on protein networks in colorectal cancer cell lines. Cell-line-specific network signatures are inferred de novo by protein quantification profiles and ultimately expose the collateral and transcript-independent effects of detrimental mutations on protein complexes.


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The Functional Impact of Alternative Splicing in Cancer

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Héctor Climente-González, Eduard Porta-Pardo, Adam Godzik, Eduardo Eyras
Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers).

Graphical abstract

Teaser

Climente-González et al. show that alternative splicing (AS) changes in tumors are linked to a significant loss of functional domain families that are also frequently mutated in cancer. These domain losses happen independently of somatic mutations and lead to the remodeling of complexes and protein-protein interactions in cancer.


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Generation of Mouse Haploid Somatic Cells by Small Molecules for Genome-wide Genetic Screening

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Zheng-Quan He, Bao-Long Xia, Yu-Kai Wang, Jing Li, Gui-Hai Feng, Lin-Lin Zhang, Yu-Huan Li, Hai-Feng Wan, Tian-Da Li, Kai Xu, Xue-Wei Yuan, Yu-Fei Li, Xin-Xin Zhang, Ying Zhang, Liu Wang, Wei Li, Qi Zhou
The recent success of derivation of mammalian haploid embryonic stem cells (haESCs) has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn²⁺-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.

Graphical abstract

Teaser

He et al. show that CDK1 and ROCK inhibition can suppress the spontaneous diploidization of haploid embryonic stem cells (haESCs) and generate haploid somatic cells of all three germ layers for genome-wide genetic screening.


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Mass Cytometry and Topological Data Analysis Reveal Immune Parameters Associated with Complications after Allogeneic Stem Cell Transplantation

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Tadepally Lakshmikanth, Axel Olin, Yang Chen, Jaromir Mikes, Erik Fredlund, Mats Remberger, Brigitta Omazic, Petter Brodin
Human immune systems are variable, and immune responses are often unpredictable. Systems-level analyses offer increased power to sort patients on the basis of coordinated changes across immune cells and proteins. Allogeneic stem cell transplantation is a well-established form of immunotherapy whereby a donor immune system induces a graft-versus-leukemia response. This fails when the donor immune system regenerates improperly, leaving the patient susceptible to infections and leukemia relapse. We present a systems-level analysis by mass cytometry and serum profiling in 26 patients sampled 1, 2, 3, 6, and 12 months after transplantation. Using a combination of machine learning and topological data analyses, we show that global immune signatures associated with clinical outcome can be revealed, even when patients are few and heterogeneous. This high-resolution systems immune monitoring approach holds the potential for improving the development and evaluation of immunotherapies in the future.

Graphical abstract

Teaser

Lakshmikanth et al. conduct a systems analysis of immune reconstitution after stem cell transplantation. Using topological data analysis, combinations of cells and proteins associated with CMV and graft-versus-host disease were revealed and illustrate the potential of systems immunomonitoring to improve the development and evaluation of cancer immunotherapies.


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Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Anne Rechtien, Laura Richert, Hadrien Lorenzo, Gloria Martrus, Boris Hejblum, Christine Dahlke, Rahel Kasonta, Madeleine Zinser, Hans Stubbe, Urte Matschl, Ansgar Lohse, Verena Krähling, Markus Eickmann, Stephan Becker, Rodolphe Thiébaut, Marcus Altfeld, Marylyn Addo
Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.

Graphical abstract

Teaser

Rechtien et al. apply a systems vaccinology approach to examine the early innate immune responses elicited by the Ebola vaccine rVSV-ZEBOV. They find that early innate immune responses, with IP-10 as an independent soluble marker, correlate with EBOV-GP-specific antibody induction.


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Are Optimism and Cynical Hostility Associated with Smoking Cessation in Older Women?

Abstract

Background

Optimism and cynical hostility independently predict morbidity and mortality in Women's Health Initiative (WHI) participants and are associated with current smoking. However, their association with smoking cessation in older women is unknown.

Purpose

The purpose of this study is to test whether optimism (positive future expectations) or cynical hostility (mistrust of others) predicts smoking cessation in older women.

Methods

Self-reported smoking status was assessed at years 1, 3, and 6 after study entry for WHI baseline smokers who were not missing optimism or cynical hostility scores (n = 10,242). Questionnaires at study entry assessed optimism (Life Orientation Test-Revised) and cynical hostility (Cook-Medley, cynical hostility subscale). Generalized linear mixed models adjusted for sociodemographics, lifestyle factors, and medical and psychosocial characteristics including depressive symptoms.

Results

After full covariate adjustment, optimism was not related to smoking cessation. Each 1-point increase in baseline cynical hostility score was associated with 5% lower odds of cessation over 6 years (OR = 0.95, CI = 0.92–0.98, p = 0.0017).

Conclusions

In aging postmenopausal women, greater cynical hostility predicts lower smoking cessation over time. Future studies should examine whether individuals with this trait may benefit from more intensive cessation resources or whether attempting to mitigate cynical hostility itself may aid smoking cessation.

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Associations Between Pain Catastrophizing and Cognitive Fusion in Relation to Pain and Upper Extremity Function Among Hand and Upper Extremity Surgery Patients

Abstract

Background

Patients who present to hand surgery practices are at increased risk of psychological distress, pain, and disability. Greater catastrophic thinking about pain is associated with greater pain intensity, and initial evidence suggest that, together, catastrophic thinking about pain and cognitive fusion (i.e., interpretation of thoughts as true) are associated with poorer pain outcomes.

Purpose

We tested whether cognitive fusion or catastrophic thinking interacts in relation to pain and upper extremity physical function among patients seeking care from a hand surgeon.

Methods

Patients (N = 110; mean age= 47.51; 59% women) presenting to an outpatient hand surgery practice completed computerized measures of sociodemographics, pain intensity, cognitive fusion, catastrophic thinking about pain, and upper extremity function.

Results

ANCOVA revealed an interaction between cognitive fusion and catastrophic thinking about pain with respect to pain intensity and upper extremity function (ps < .01). Participants who scored high on both cognitive fusion and catastrophic thinking about pain reported the greatest levels of pain, relative to those who scored high on a single measure. The lowest levels of upper extremity function were also observed among those who scored high on both catastrophic thinking about pain and cognitive fusion. A similar pattern of results was observed when we tested each catastrophizing subscale individually.

Conclusion

Maladaptive cognitions about pain (i.e., catastrophic thinking) may be particularly problematic when interpreted as representative of reality (i.e., cognitive fusion). Psychosocial interventions addressing catastrophic thinking about pain and cognitive fusion concurrently merit investigation among people with hand and upper extremity illness.

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Monetary Incentive Interventions Can Enhance Psychological Factors Related to Fruit and Vegetable Consumption

Abstract

Background

Incentive interventions have gained popularity to motivate health behavior change, but some psychological theorists caution that they may have deleterious effects on factors that potentiate behavior maintenance. Importantly, no empirical study has tested whether incentives indeed have iatrogenic effects on key psychological constructs associated with health behavior change and maintenance.

Purpose

The study aims to explore the effects of monetary incentives on theoretically informed psychological constructs and fruit and vegetable consumption.

Methods

Individuals reporting insufficient fruit and vegetable consumption were randomly assigned to receive either daily monetary incentives, delayed monetary incentives, or no incentives for their fruit and vegetable consumption during a 3-week intervention period. Behavior engagement and psychological factors were measured at baseline, at the end of the intervention, and 2 weeks following the cessation of the intervention.

Results

Participants in the daily incentive condition demonstrated the greatest increase in self-reported consumption during the intervention and at the follow-up. Moreover, increases in consumption during the intervention period were associated with increases in attitudes and self-efficacy, which, in turn, predicted behavior maintenance at follow-up. Intrinsic motivation to consume fruits and vegetables increased over time across the entire sample but did not differ between groups.

Conclusions

Monetary incentives can alter health behavior engagement without decreasing intrinsic motivation or other relevant cognitive and motivational constructs. Further, although incentives may serve as a vehicle to initiate behavior change, increased experience with the behavior may then lead to enhancements in key psychological constructs that serve as mechanisms to potentiate behavior maintenance following the cessation of incentives.

Trial Registration Number

The trial was registered with the ClinicalTrials.gov database (NCT02594319) http://ift.tt/2x2E7bw.

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Preventing Weight Gain Improves Sleep Quality Among Black Women: Results from a RCT

Abstract

Background

Obesity and poor sleep are highly prevalent among Black women.

Purpose

We examined whether a weight gain prevention intervention improved sleep among Black women.

Methods

We conducted a randomized trial comparing a 12-month weight gain prevention intervention that included self-monitoring through mobile technologies and phone coaching to usual care in community health centers. We measured sleep using the Medical Outcomes Study Sleep Scale at baseline, 12 months, and 18 months. The scale examines quantity of sleep, sleep disturbance, sleep adequacy, daytime somnolence, snoring, shortness of breath, and global sleep problems (sleep problem indices I and II).

Results

Participants (n = 184) were on average 35.4 years and obese (BMI 30.2 kg/m²); 74% made <$30,000/year. At baseline, average sleep duration was 6.4 (1.5) hours. Controlling for weight change and sleep medication, the intervention group reported greater improvements in sleep disturbance [−8.35 (−16.24, −0.45)] and sleep problems at 12 months: sleep problem index I [−8.35 (−16.24, −0.45)]; sleep problem index II [−8.35 (−16.24, −0.45)]. However, these findings did not persist at 18 months.

Conclusions

Preventing weight gain may afford clinical benefit on improving sleep quality.

Trial Registration Number

The trial was registered with the ClinicalTrials.gov database (NCT00938535)

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Accumulation of Depressive Symptoms and Carotid Intima-Media Thickness: the Cardiovascular Risk in Young Finns Study

Abstract

Background

The association between depressive symptoms and subclinical atherosclerosis has been inconsistent.

Purpose

We sought to replicate our previous study, which demonstrated a positive relation between depressive symptoms and subclinical atherosclerosis assessed with carotid intima-media thickness (IMT) in men, using a newer measurement of carotid IMT and a cumulative loading of depressive symptoms over three follow-ups.

Methods

The sample comprised 996 adults (352 men) aged 30 to 45 years in 2007 from a prospective population-based Finnish sample. The participants completed a modified version of Beck Depression Inventory in 1992, 1997, and 2001. Carotid IMT was assessed with ultrasound in 2001 and 2007. Cardiovascular risk factors (i.e., body mass index, systolic blood pressure, low-density lipoprotein cholesterol, and smoking) were measured in childhood (1980) and in adulthood (2007).

Results

We found no association between the accumulative depression index and carotid IMT before or after controlling for the traditional risk factors (all p values ≥0.67). Depressive symptoms did not predict IMT progression over two time points and the highest level of carotid wall thickening. Imputed and non-imputed data sets provided similar results. Results remained the same when men and women were analyzed separately. Additional analyses revealed no significant interactions between depressive symptoms and cardiovascular risk factors (i.e., body mass index and systolic blood pressure) on carotid IMT (all p values >0.15).

Conclusions

The findings of this population-based study did not indicate any direct association between depressive symptoms and carotid IMT in asymptomatic, young adults.

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Prospective Associations Between Depressive Symptoms and the Metabolic Syndrome: the Spirited Life Study of Methodist Pastors in North Carolina

Abstract

Background

Metabolic syndrome (Met-S) has a robust concurrent association with depression. A small, methodologically limited literature suggests that Met-S and depression are reciprocally related over time, an association that could contribute to their overlapping influences on morbidity and mortality in cardiovascular disease, diabetes, and cancer.

Purpose

Using a refined approach to the measurement of Met-S as a continuous latent variable comprising continuous components, this study tested the prospective associations between Met-S and depression.

Methods

This study of 1114 clergy included four annual assessments of depressive symptoms and Met-S components. Standard methods were used to measure Met-S risk factors, and the Patient Health Questionnaire-8 was used to assess depressive symptoms. We used confirmatory factor analysis to verify the structure of Met-S and depression and structural equation modeling to quantify the prospective relationships.

Results

The statistical models confirmed the validity of quantifying Met-S as a continuous latent variable, replicated previous evidence of a concurrent association, and indicated a significant prospective association of initial depressive symptoms with subsequent Met-S. Initial Met-S was at most only weakly associated with subsequent depressive symptoms, and the former prospective effect was significantly larger. Associations of depressive symptoms and Met-S were significant for both men and women, but somewhat stronger among men.

Conclusions

Results support representation of Met-S as a continuous latent variable. The association of initial depressive symptoms with later Met-S suggests that interventions addressing these correlated risk factors may prove useful in preventive efforts.

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Increasing Physical Activity Through Principles of Habit Formation in New Gym Members: a Randomized Controlled Trial

Abstract

Background

The promotion of physical activity (PA) is paramount to public health, yet interventions in the social cognitive tradition have yielded negligible improvements. The limited progression may be due to an overreliance on intention as the proximal determinant of behavior and a lack of consideration of implicit/automatic processes. The purpose of this study was to examine the impact of a habit formation intervention on PA over 8 weeks in a two-arm parallel design, randomized controlled trial.

Methods

Participants (n = 94) were new gym members with the intention to engage in PA but below international PA guidelines at baseline, who were randomized into a control or habit experimental group. The experimental group attended a workshop (at baseline) and received a follow-up booster phone call at week 4. The primary outcome of the study was minutes of moderate-vigorous intensity PA (MVPA) at week 8. The secondary outcome was a manipulation check to determine if the experimental group effectively incorporated habit-building constructs (cues and practice consistency).

Results

The experimental group showed a significant increase in MVPA after 8 weeks in both accelerometry (d = 0.39, p = .04) and self-report (d = 0.53, p = .01) compared with the control group. The experimental group also showed an increase in use of cues (d = 0.56, p < .001) and practice consistency (d = 0.40, p = .01) at week 8.

Conclusion

The results contribute to the initial validity of increasing PA through a focus on preparation cues and practice consistency. Future research should replicate these findings and extend the duration of assessment to evaluate whether PA changes are sustained.

Registered Trial Number NCT02785107

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Development of prediction equations for estimating appendicular skeletal muscle mass in Japanese men and women

This study aimed to develop and cross-validate prediction equations for estimating appendicular skeletal muscle mass (ASM) and to examine the relationship between sarcopenia defined by the prediction equations...

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