An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis

Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in pl...

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Supporting Treatment Adherence Readiness through Training (START) for patients with HIV on antiretroviral therapy: study protocol for a randomized controlled trial

Few HIV antiretroviral adherence interventions target patients before they start treatment, assess adherence readiness to determine the timing of treatment initiation, or tailor the amount of adherence support...

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Comparison of exenatide with biphasic insulin aspart 30 on glucose variability in type 2 diabetes: study protocol for a randomized controlled trial

Apart from the mean level of glycemic control, the extent of glucose excursions is another important issue to consider in type 2 diabetes mellitus (T2DM) management. Studies have showed that fluctuations of gl...

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Morita therapy for depression and anxiety (Morita Trial): study protocol for a pilot randomised controlled trial

Morita Therapy, a psychological therapy for common mental health problems, is in sharp contrast to established western psychotherapeutic approaches in teaching that undesired symptoms are natural features of h...

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A case report of immunosuppression-related Kaposi’s sarcoma after autologous stem cell transplantation

Kaposi's sarcoma (KS) is a tumor formed by angioproliferations driven by Human herpes virus 8 also known as Kaposi's sarcoma-associated herpes virus (KSHV). It is best known as an acquired immune deficiency sy...

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Blinding in randomized controlled trials in general and abdominal surgery: protocol for a systematic review and empirical study

Blinding is a measure in randomized controlled trials (RCT) to reduce detection and performance bias. There is evidence that lack of blinding leads to overestimated treatment effects. Because of the physical c...

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High Throughput Assay to Examine Egg-Laying Preferences of Individual Drosophila melanogaster

This protocol describes a high throughput assay for testing egg-laying preferences of Drosophila melanogaster at single-animal resolution. This assay provides a simple, efficient, and scalable platform to identify genes and circuit components that control a simple decision-making process.

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Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions

OBJECTIVE: The present study aims to investigate the correlation between serum level of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the severity of coronary arterial lesion in patients with coronary heart disease (CHD).

PATIENTS AND METHODS: Between August 2010 and January 2015, 126 CHD patients and 70 patients with coronary arterial stenosis < 50% (controls) were included in the present study. Serum PCSK9 level was determined using ELISA. Demographic characteristics, relevant clinical data and biochemical data were collected from all patients, and their relationship with PCSK9 was analyzed to evaluate the correlation of PCSK9 expression with the severity of coronary artery disease (CAD).

RESULTS: Concentrations of total cholesterol (TC) and fasting blood sugar (FBS) were significantly higher in CHD patients than in controls (p < 0.05). No significant differences were observed in gender, age, body mass index (BMI), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), family history, smoking history and history of hypertension between groups (p > 0.05). Serum PCSK9 levels in the CHD group were significantly higher than those in the control group [(96.4 ± 33.2) ng/mL vs. (81.8 ± 27.6) ng/mL, p < 0.05]. Compared with those of patients with single-vessel or double-vessel disease, PCSK9 levels were significantly elevated in patients with multi-vessel disease (p < 0.05). The Gensini score of the CHD group was significantly lower than that of the control group (11.4 ± 10.5 vs. 37.3 ± 10.3, p < 0.05). The Gensini score of patients with multi-vessel disease was significantly higher compared with patients of single-vessel  or double-vessel disease (p < 0.05). Correlation analysis revealed that PCSK9 was positively correlated with many clinical parameters, including age, BMI, TC, TG, systolic blood pressure, FBS, Gensini score and LDL-C (p < 0.05). However, PCSK9 was not correlated with either gender ratio or diastolic blood pressure (p > 0.05).

CONCLUSIONS: Serum PCSK9 level is significantly elevated in CHD patients and its variation is correlated with the severity of CAD.

L'articolo Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions sembra essere il primo su European Review.

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Clinical observation on pericardiocentesis and glucocorticoid in the treatment of tuberculous pericarditis

OBJECTIVE: To investigate pericardiocentesis and glucocorticoids in the treatment of the clinical curative effect of tuberculous pericarditis.

PATIENTS AND METHODS: Choose 128 cases of our hospital diagnosed as tuberculous pericarditis patients as the research object, according to the treatment, were divided into group A (pericardium puncture + anti-tuberculosis (anti-TB) treatment of 26 cases) and group B (pericardium puncture +anti-tuberculosis (anti-TB) + glucocorticoid treatment of 30 cases), group C (anti-tuberculosis (anti-TB) + 24 cases of glucocorticoid therapy), and group D (48 cases of anti-tuberculosis (anti-TB) treatment), in the treatment of 8 weeks, 3 months, 6 months, 9 months, 12 months, 18 months by B ultrasonic and CT examination to observe the efficacy of treatment.

RESULTS: At 8 weeks after treatment in group A, group B and group C and group D efficient were 61.54%, 93.33%, 54.17%, and 68.75%, respectively, group B, respectively, compared with group A, group C, and group D, had obvious statistical significance difference (p < 0.05); Groups of early and late treatment comparison difference have no statistical significance (p > 0.05).

CONCLUSIONS: Tuberculous pericarditis in anti-TB treatment on the basis of using pericardiocentesis and sugar cortical hormone treatment, can achieve an ideal effect.

L'articolo Clinical observation on pericardiocentesis and glucocorticoid in the treatment of tuberculous pericarditis sembra essere il primo su European Review.

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Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by signal-averaged P wave duration and P wave dispersion

OBJECTIVE: Aortic regurgitation, conduction disturbances, increased myocardial fibrosis and pericarditis could be seen in ankylosing spondylitis (AS). However, less attention has been paid to supraventricular arrhythmias (SVA) and atrial conduction system changes. We aimed to assess SVA and conduction system changes in patients with AS.

PATIENTS AND METHODS: Twenty-eight patients (24 men; mean age, 28.7 ± 5.7 years) with AS and 30 healthy volunteers (26 men; mean age, 29.3 ± 5.8 years) were enrolled. All subjects were evaluated by 24-hour ambulatory electrocardiogram, 12 lead standard electrocardiogram (ECG) for P wave dispersion (Pd), and signal-averaged ECG (SAECG) for P wave duration (SAPWD).

RESULTS: SVAs were detected in 9 patients with AS (32%) and 3 controls (10%; p =0.02). Mean SAPWD (115.7±28.6 ms vs. 100.2 ± 18.7 ms, p =0.017) and mean Pd (11.9±4.8 ms vs. 9.3±3.6 ms, 0.023) was longer in patients with AS than the control group. When patient with AS were divided into 2 subgroups as patients with or without SVA, the Pd (16.2±5.0 vs. 9.9±3.2, p =0.001), SAPWD (151.4±7.8 vs. 98.7±16.1, p =0.001) and Bath ankylosing spondylitis disease activity index (BASDAI) (5.1±1.6 vs. 3.7±1.0, p =0.014) were significantly greater in the subgroup with arrhythmias compared to the subgroup without arrhythmias. There was a strong positive correlation between BASDAI and SAPWD (r=0.622, p =0.001). There was also a moderate positive correlation between BASDAI and SAPWD (r=0.479, p =0.01).

CONCLUSIONS: SVA were detected more frequently in AS than control group. SAPWD and Pd were prolonged in patients with AS. Clinical severity assessed with BASDAI had a positive correlation with prolongation of SAPWD and Pd.

L'articolo Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by signal-averaged P wave duration and P wave dispersion sembra essere il primo su European Review.

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USP4 promotes invasion of breast cancer cells via Relaxin/TGF-β1/Smad2/MMP-9 signal

OBJECTIVE: Ubiquitin-specific protease 4 (USP4) is a deubiquitinating enzyme with key roles in the regulation of TGF-β1 signaling, suggesting its importance in tumorigenesis. However, the underlying mechanisms causing this are not entirely clear. In the present study, we investigated the effect of USP4 on invasion and tumorigenesis of breast cancer cells, and explored its mechanism.

MATERIALS AND METHODS: Effects of USP4 overexpression or USP4 silencing by small interfering RNA (USP4 siRNA) on invasion of breast cancer MDA-MB-231 and T47D cells in vitro was detected. Using siRNAs and inhibitors to examine the USP4 signaling pathway.

RESULTS: The migration and invasion assays showed that USP4 promotes human breast cancer cell migration and invasion by USP4 overexpression, and knockdown of USP4 by siRNA inhibits human breast cancer cell migration and invasion. Treatment with RLX siRNAs, TGF-β1 siRNAs, Smad2 siRNAs or BB94 (MMPs inhibitor) to USP4-overexpressing breast cancer cells revealed that USP4- induced RLX via TGF-β1 pathway promotes the cell migration and invasion. Further studies demonstrated that USP4-mediated TGF-β1 activation not only enhances the phosphorylation of Smad2 through TGF-β, but also directly upregulate matrix metalloproteinase (MMP)-9-mediated cell migration and invasion of breast cancer cells.

CONCLUSIONS: Therapies targeting the USP4 inhibits invasion of breast cancer cells via Relaxin/TGF-β1/Smad2/MMP-9 signal. These results indicate that USP4 is an attractive target for breast cancer therapy.

L'articolo USP4 promotes invasion of breast cancer cells via Relaxin/TGF-β1/Smad2/MMP-9 signal sembra essere il primo su European Review.

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MicroRNA-138 inhibits proliferation of cervical cancer cells by targeting c-Met

OBJECTIVE: MicroRNAs (miRNAs) function as important post-transcriptional regulators involved in a wide range of biological behaviors. MicroRNA-138 (miR-138) has been shown to play a critical role in tumor pathogenesis, the present study aimed to investigate the role of miR-138 in cervical cancer.

MATERIALS AND METHODS: CCK-8 assay was performed to measure the viabilities of cancer cells. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the mRNA and protein expression, respectively. Moreover, the miRNA target genes were validated with luciferase activity assay.

RESULTS: In the current study, we found that the expression of miR-138 was significantly down-regulated in cervical cancer tissues compared to the adjacent non-cancer tissues. CCK-8 assay showed that over-expression of miR-138 suppressed the proliferation of four cervical cancer cell lines including HeLa, SiHa, C33A and CaSki. By contrast, down-regulation of miR-138 promoted the growth of cervical cancer cells. In addition, increased expression of miR-138 led to a reduction in c-Met expression, whereas inhibition of miR-138 enhanced c-Met levels in cervical cancer cells. The luciferase reporter assay showed that c-Met was a direct target of miR-138 in cervical cancer cells.

CONCLUSIONS: These findings demonstrated that miR-138 inhibited cervical cancer cells proliferation via c-Met, providing a novel target for the molecular treatment of cervical cancer.

L'articolo MicroRNA-138 inhibits proliferation of cervical cancer cells by targeting c-Met sembra essere il primo su European Review.

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Impact of Aging on Mitochondrial Function in Cardiac and Skeletal Muscle

Publication date: Available online 24 March 2016
Source:Free Radical Biology and Medicine
Author(s): R.T. Hepple
Both skeletal muscle and cardiac muscle are subject to marked structural and functional impairment with aging and these changes contribute to the reduced capacity for exercise as we age. Since mitochondria are involved in multiple aspects of cellular homeostasis including energetics, reactive oxygen species signaling, and regulation of intrinsic apoptotic pathways, defects in this organelle are frequently implicated in the deterioration of skeletal and cardiac muscle with aging. On this basis, the purpose of this review is to evaluate the evidence that aging causes dysfunction in mitochondria in striated muscle with a view towards drawing conclusions about the potential of these changes to contribute to the deterioration seen in striated muscle with aging. As will be shown, impairment in respiration and reactive oxygen species emission with aging are highly variable between studies and seem to be largely a consequence of physical inactivity. On the other hand, both skeletal and cardiac muscle mitochondria are more susceptible to permeability transition and this seems a likely cause of the increased recruitment of mitochondrial-mediated pathways of apoptosis seen in striated muscle. The review concludes by examining the role of degeneration of mitochondrial DNA versus impaired mitochondrial quality control mechanisms in the accumulation of mitochondria that are sensitized to permeability transition, whereby the latter mechanism is favored as the most likely cause.



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Inhibition of the JNK signaling pathway increases sensitivity of hepatocellular carcinoma cells to cisplatin by down-regulating expression of P-glycoprotein

OBJECTIVE: The resistance of hepatocellular carcinoma (HCC) to chemotherapy may be mediated by the c-Jun N-terminal kinase (JNK) pathway. We wished to verify the involvement of this pathway in resistance of HCC cells to cisplatin.

MATERIALS AND METHODS: We used HepG2 cell line and cisplatin-resistant clone (HepG2/DDP). Expressions of drug resistance and apoptosis-related genes were analyzed by qPCR. Protein expressions were assessed by Western blot. The JNK pathway was assessed as total JNK1/2 and JNK1/2 phosphorylation. Cell growth kinetics was quantified by the CCK-8 assay, and cell apoptosis (Annexin V / propidium iodide) by flow cytometry.

RESULTS: HepG2/DDP cells were more resistant and less apoptotic on cisplatin. Expression of drug-resistance genes MDR1, MRP1 and MPR2 was significantly up-regulated in HepG2/DDP cells (p < 0.05), with up-regulation of MDR1 being the highest. This was confirmed by Western blot analysis of P-glycoprotein (P-gp), MRP1 and MRP2 proteins, the proteins encoded by the above genes. Expression of anti-apoptotic genes Bcl-2 and Bcl-XL was significantly up-regulated, and expression of pro-apoptotic genes Bak and Bad was significantly reduced, in HepG2/DDP cells (p < 0.05). Cisplatin treatment of HepG2 led to increased phosphorylation of JNK1/2; the trend reversed by the inhibitor SP600125. Furthermore, cisplatin increased expression of P-gp, which was also attenuated by SP600125. Cell growth was inhibited more substantially, and cell apoptosis promoted, when HepG2 cells were exposed to both cisplatin and SP600125.

CONCLUSIONS: Inhibition of the JNK signaling pathway enhances the sensitivity of HCC cells to cisplatin by down-regulating the expression of P-gp.

L'articolo Inhibition of the JNK signaling pathway increases sensitivity of hepatocellular carcinoma cells to cisplatin by down-regulating expression of P-glycoprotein sembra essere il primo su European Review.

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Mechanism of action of EBV, Bcl-2, p53, c-Myc and Rb in non-Hodgkin’s lymphoma

OBJECTIVE: The aim of the present study is to explore the mechanism of action of several proteins, including Epstein-Barr virus (EBV), B-cell lymphoma (Bcl)-2, p53, c-Myc and retinoblastoma (Rb), in Non-Hodgkin's lymphoma (NHL).PATIENTS AND METHODS: Between July 2010 and July 2015, samples of 142 patients with pathologically confirmed NHL which presented at our institution were included in the observation group. In addition, samples from 55 patients with hyperplastic lymphadenitis presented during the same period were enrolled as control group. The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+) were determined and compared

PATIENTS AND METHODS: Between July 2010 and July 2015, samples of 142 patients with pathologically confirmed NHL which presented at our institution were included in the observation group. In addition, samples from 55 patients with hyperplastic lymphadenitis presented during the same period were enrolled as control group. The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+) were determined and compared among different subtypes and stages of NHLs of observation group. Besides, the correlation of EBV with p53, Bcl-2, Rb and c-Myc were investigated in NHLs of observation group.

RESULTS: In the observation group, the expression rates of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were significantly higher than those, respectively, in the control group (p < 0.05). No significant correlation was observed between EBV expression and the expressions of p53, Bcl-2, Rb and c-Myc in the observation group (p > 0.05). The expression rates of p53(+) and Bcl-2(+) were significantly higher in aggressive and highly-aggressive NHLs than in indolent NHLs of the observation group (p < 0.05). The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were significantly higher in stage III-IV NHLs than in stage I-II NHLs (p < 0.05).

CONCLUSIONS: The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) are closely associated with NHL pathogenesis. Expressions of these proteins are higher in later stages of NHLs, and expressions of p53(+) and Bcl-2(+) are higher in more aggressive NHLs.

L'articolo Mechanism of action of EBV, Bcl-2, p53, c-Myc and Rb in non-Hodgkin's lymphoma sembra essere il primo su European Review.

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DTC chemotherapy regimen is associated with higher incidence of premature ovarian failure in women of reproductive age with breast cancer

OBJECTIVE: Different chemotherapy regimens may contribute differently to the development of Premature Ovarian Failure (POF) in women of reproductive age with breast cancer. Here we evaluated how two different chemotherapy regimens, CAF (tegafur + pirarubicin + ifosfamide) and DTC (docetaxel + pirarubicin + ifosfamide), affect the development of POF.

PATIENTS AND METHODS: We enrolled 164 women of reproductive age with breast cancer (mean ± SD age of 34.56 ± 9.48 years). The patients were divided into two groups, which were respectively treated with CAF (n = 89) or DTC (n = 75) chemotherapy regimen. Both study groups were comparable in all analyzed characteristics at baseline. Patients were treated with respective chemotherapy regimen for 6 months and followed up for over 12 months after completion of chemotherapy. Study outcomes were occurrence rates of POF, menstrual status and recovery after completion of chemotherapy, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and oestradiol (E2).

RESULTS: At 6 months after completion of chemotherapy, POF incidence rates were significantly lower in the CAF group. Furthermore, the proportion of patients with eumenorrhea, menstrual disorders or chemotherapy-induced amenorrhea in this study group was also significantly different from the DTC group. Similarly, adverse changes of serum levels of FSH, LH and E2 were less pronounced in the CAF group.

CONCLUSIONS: Both tested chemotherapy regimens can cause POF; however, adverse effects of DCT chemotherapy regimen on ovarian function are more pronounced than those by CAF chemotherapy regimen.

L'articolo DTC chemotherapy regimen is associated with higher incidence of premature ovarian failure in women of reproductive age with breast cancer sembra essere il primo su European Review.

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Decoction and Fermentation of Selected Medicinal Herbs Promote Hair Regrowth by Inducing Hair Follicle Growth in Conjunction with Wnts Signaling

It is well recognized that regulating the hair follicle cycle in association with Wnt signaling is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether selected herbal medicines processed by decoction and fermentation promote hair growth by upregulating the number and size of hair follicles and Wnt signaling, including activation of β-catenin and Akt in telogen-synchronized C57BL/6N mice. The results revealed that the fermented extract after decoction (FDE) more effectively promoted hair growth than that of a nonfermented extract (DE). Notably, FDE effectively enhanced formation of hair follicles with clearer differentiation between the inner and outer root sheath, which is observed during the anagen phase. Mechanistic evidence was found for increased β-catenin and Akt phosphorylation levels in dorsal skin tissue along with elevated expression of hair regrowth-related genes, such as Wnt3/10a/10b, Lef1, and fibroblast growth factor 7. In conclusion, our findings suggest that FDE plays an important role in regulating the hair cycle by increasing expression of hair regrowth-related genes and activating downstream Wnt signaling targets.

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MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease

Publication date: Available online 24 March 2016
Source:Free Radical Biology and Medicine
Author(s): Shelly C Lu, José M. Mato, Cristina Espinosa-Diez, Santiago Lamas
The discovery of the microRNA (miRNA) family of small RNAs as fundamental regulators of post-transcriptional gene expression has fostered research on their importance in every area of biology and clinical medicine. In the particular area of liver metabolism and disease, miRNAs are gaining increasing importance. By focusing on two fundamental hepatic biosynthetic pathways, glutathione and methionine, we review recent advances on the comprehension of the role of miRNAs in liver pathophysiology and more specifically of models of hepatic cholestasis/fibrosis and hepatocellular carcinoma.



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Association between pain catastrophising and musculoskeletal disorders is modified by past injuries in Malaysian military recruits

Objectives

Pain catastrophising is defined as exaggerated negative thoughts, which can occur during an actual or anticipated painful experience, such as musculoskeletal injuries (MSI) or disorders (MSD). The aims of this study are to examine the association between pain catastrophising and MSI and MSD in Malaysian Army male recruits, and evaluate the effects of past injury.

Methods

A cohort of 611 male Malaysian Army recruits were recruited and followed up at 3 and 6 months. Pain catastrophising, MSD, sociodemographic and work factors were measured using a self-administered questionnaire, and MSI incidence was retrieved from the medical records. Multivariable fixed effects regression was used to model the cumulative incidence of MSD and MSI.

Results

Approximately 12% of the recruits were diagnosed with incident MSI and 80% reported incident MSD. Higher pain catastrophising at baseline was associated with higher 6 month MSD risk (adjusted OR (aOR) 1.6 per 1 SD increase of Pain Catastrophising Scale (PCS) scores; 95% CI 1.2 to 2.0), and longitudinally associated with MSD incidence (aOR 1.2, 95% CI 1.1 to 1.4). Pain catastrophising was not associated with MSI incidence (aOR 1.0, 95% CI 0.8 to 1.3). The association between pain catastrophising and self-reported MSD was stronger among recruits with self-reported past injury (p for interaction <0.001).

Conclusions

Pain catastrophising was able to predict symptomatic MSD, and not physician-diagnosed MSI, and these findings are directly related to individual health beliefs. Pain catastrophising has a greater influence on how military recruits perceived their musculoskeletal conditions during training, and efforts to reduce pain catastrophising may be beneficial.

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More From Less: High-Throughout Dual Polarity Lipid Imaging of Biological Tissues

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00169F, Paper

Shane Ellis, Jo Cappell, Nina Ogrinc Potocnik, Benjamin Balluff, Julie Hamaide, Annemie Van der Linden, Ron Heeren
The high ion signals produced by many lipids in mass spectrometry imaging make them an ideal molecular class to study compositional changes throughout tissue sections and their relationship with disease....
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Raman spectroscopy as a tool for label-free lymphocyte cell line discrimination

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00181E, Paper

Alison Jane Hobro, Yutaro Kumagai, Shizuo Akira, Nicholas I Smiith
Unactivated lymphocytes are morphologically identical and biochemically are relatively similar, making them difficult to distinguish from one another with conventional light microscopy. Here, we use Raman spectroscopy to provide biochemical...
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High level of chemokine CCL18 is associated with pulmonary function deterioration, lung fibrosis progression and reduced survival in Systemic Sclerosis

Objectives

Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18 which has been linked to pulmonary inflammation is an interesting candidate, but data have not been consistent. Here, we aimed to assess CCL18 levels in a large, prospective and unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis.

Methods

Sera from the Oslo University Hospital SSc cohort (n=298) and healthy controls (n=100) were analysed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/ml) was defined using mean value +2SD in healthy controls sera as cut-off.

Results

High serum CCL18 was identified in 35% (105/298). Annual decline in Forced Vital Capacity (FVC) differed significantly between high and low CCL18 subsets (13.3% and 4.7, p=0.016), as did the annual progression rate of lung fibrosis (0.9% (SD2.9) and 0.2% (SD1.9)). Highest rates of annual FVC decline >10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (10% (Odds Ratio (OR) 1.1, 95%CI 1.01-1.11) and FVC Conclusions

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Early Mobilization and Rehabilitation of the Critically Ill Patient

Neuromuscular disorders are increasingly recognized as a cause of both short and long-term physical morbidity in survivors of critical illness. This recognition has given rise to research aimed at better understanding the risk factors and mechanisms associated with neuromuscular dysfunction and physical impairment associated with critical illness, as well as possible interventions to prevent or treat these issues. Among potential risk factors, bed rest is an important modifiable risk factor. Early mobilization and rehabilitation of critically ill patients may help prevent or mitigate the sequelae of bed rest and improve patient outcomes. Recent research studies and quality improvement projects have demonstrated that early mobilization and rehabilitation is safe and feasible in critically ill patients, with potential benefits including improved physical functioning and decreased duration of mechanical ventilation, intensive care and hospital stay. Despite these findings, early mobilization and rehabilitation is still uncommon in routine clinical practice, with many perceived barriers. This review 1) summarizes potential risk factors for neuromuscular dysfunction and physical impairment associated with critical illness, 2) highlights the potential role of early mobilization and rehabilitation in improving patient outcomes, and 3) discusses some of the commonly perceived barriers to early mobilization and strategies for overcoming them.

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Temporary IVC Filters: How Do We Move Forward?

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Hypertension is associated with undiagnosed obstructive sleep apnea during rapid eye movement (REM) sleep

Background

Evidence linking obstructive sleep apnea (OSA) with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension.background

Methods

The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) Study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥140mm Hg and/or diastolic ≥ 90mm Hg, or medication) and risk factors. In 2010-2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography (PSG, Embletta X100) of whom739 recorded ≥30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up [56 months mean follow-up (range: 48-74)] in men free of hypertension at baseline.

Results

Severe REM OSA [apnea hypopnea index (AHI)REM ≥30/h) showed independent adjusted associations with prevalent [odds ratio (OR): 2.40, 95% confidence interval (CI): 1.42-4.06], and recent-onset hypertension (2.24, 1.04-4.81). Significant associations with non-REM AHI (AHINREM) were not seen. In men with AHIConclusions

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Oropharyngeal crowding closely relates to aggravation of obstructive sleep apnea

Background

Obesity is known to be an important risk factor for obstructive sleep apnea (OSA). However, OSA can also be seen in non-obese patients with a small maxilla and/or mandible, as well as in all obese patients with such features. Thus, we hypothesized that regional factors, oropharyngeal crowding associated with fat deposition, and maxillomandibular enclosure size closely related to the severity of OSA.

Methods

A total of 703 male Japanese subjects, who were classified into obese (body mass index [BMI] ≥ 30 kg/m2; n=158) and non-obese (BMI Results

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Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: the Sleep Apnea Stress Randomized Controlled Trial

Background

Although existing research highlights the relationship of obstructive sleep apnea (OSA) and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures.

Methods

We conducted a parallel, randomized controlled trial in moderate to severe OSA (Apnea-Hypopnea Index>15) patients to examine effects of 2-month continuous positive airway pressure (CPAP) versus sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes:ng/mg) and myeloperoxidase:pmol/L)) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95%CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia.

Results

Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In intent to treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.05, -0.15-0.06 versus -0.13, -0.23- -0.02) or myeloperoxidase (-3.33, -17.02-10.37 versus -5.15, -18.65-8.35), nor other oxidative markers; findings which persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/ml) levels (-0.04, -0.08- -0.01 versus 0.02, -0.02-0.06, p=0.019) and augmentation index (%) (-6.49, -9.32, -3.65 versus 0.44, -2.22, 3.10, pConclusions

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A Multidisciplinary Pulmonary Embolism Response Team (PERT) –Initial 30-Month Experience with a Novel Approach to Delivery of Care to Patients with Sub-Massive and Massive PE

Introduction

Integrating newly developed tests and treatments for severe pulmonary embolism (PE) into clinical care requires coordinated multi-specialty collaboration. To meet this need, we developed a new paradigm: a multidisciplinary Pulmonary Embolism Response Team (PERT). In this report, we provide the first longitudinal analysis of patients treated by a PERT.

Methods

Our PERT includes specialists in cardiovascular medicine and surgery, emergency medicine, hematology, pulmonary/critical care and radiology and is organized as a rapid response team. We prospectively captured clinical, therapeutic and outcome data at PERT activation and during follow-up periods up to 365 days. We analyzed data collectively, and as five mutually exclusive six-month time periods. We performed Fisher's exact tests and regression analysis to test for trend.

Results

In 30 months, there were 394 unique PERT activations, 314 (80%) for confirmed PE. PERT activations increased by 16% every six months. Most confirmed PE were submassive (n=143, 46%) or massive (n=80, 26%). The PERT treated a relatively large proportion of PE patients with systemic or catheter-directed thrombolysis (n=35, 11%), though the most common treatment was anticoagulation alone (n=215, 69%). Hemorrhagic complications were rare overall, especially among patients treated with catheter-directed thrombolysis. The all cause 30-day mortality of PERT patients with confirmed PE was 12%.

Conclusions

We report our initial 30-month experience with a novel multidisciplinary PERT that rapidly engages multiple specialists to deliver efficient, organized and evidence-based care to patients with high-risk PE. The PERT paradigm was rapidly adopted and may become a new standard-of-care for patients with PE.

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Recent Advances in Chest Medicine: Advances in Bronchial Thermoplasty

Bronchial thermoplasty (BT) is a therapeutic intervention for patients with severe persistent asthma that delivers targeted thermal energy to the airway walls with the goal of ablating the smooth muscle. Since the publication of the original pre-clinical studies, three large randomized clinical trials evaluating its impact on asthma control have been performed. These trials have shown improvements in asthma related quality of life and a reduction in asthma exacerbations following treatment with BT. However, there remains significant controversy regarding the true efficacy of BT and the interpretation of these studies, particularly the Asthma Intervention Research (AIR)-2 trial. Here, we will discuss these controversies and present the latest evidence on the use of BT in asthma, specifically the recently published 5-year longitudinal evaluation of patients. In addition, we will discuss new insights into the histopathologic changes that occur in the airways following BT as well as the feasibility of performing the procedure in very severe asthmatics. We will also discuss the ongoing translational and clinical investigations regarding the underlying mechanism of action and methods to improve patient selection for this procedure.

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Elevated levels of circulating BMP7 predict mortality in pulmonary arterial hypertension

Background

This study aimed to show whether circulating BMPs levels are associated with increased risk of mortality in PAH patients.

Methods

A total of 156 PAH patients including 43 HPAH and 113 IPAH diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from HPAH (n = 43), IPAH (n = 113) and controls (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMPs levels.

Results

HPAH patients had significantly higher BMP7 concentrations than IPAH and controls (20.1 (9.4, 55.2) vs. 6.5 (3.5, 11.7) and 2.5 (0.9, 6.6) pg/ml, respectively; P Conclusions

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Inside front cover continued (editorial board members)

Publication date: April 2016
Source:Biological Psychology, Volume 116





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Editorial board

Publication date: April 2016
Source:Biological Psychology, Volume 116





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Deficient Aversive-potentiated Startle and the Triarchic Model of Psychopathy: The Role of Boldness

Publication date: Available online 24 March 2016
Source:Biological Psychology
Author(s): Àngels Esteller, Rosario Poy, Javier Moltó
This study examined the contribution of the phenotypic domains of boldness, meanness, and disinhibition of the Triarchic conceptualization of psychopathy (Patrick, Fowles & Krueger, 2009) to deficient aversive-potentiated startle in a mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes were recorded during a passive picture-viewing task (erotica, neutral, threat, and mutilation). Deficient threat vs. neutral potentiation was uniquely related to increased boldness scores, thus suggesting that the diminished defensive reaction to aversive stimulation is specifically linked to the charm, social potency and venturesomeness features of psychopathy (boldness), but not to features such as callousness, coldheartedness and cruelty traits (meanness), even though both phenotypes theoretically share the same underlying low-fear disposition. Our findings provide further evidence of the differential association between distinct psychopathy components and deficits in defensive reactivity and strongly support the validity of the triarchic model of psychopathy in disentangling the etiology of this personality disorder.



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Impact of migration on tuberculosis epidemiology and control in the EU/EEA

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Epidemiological characteristics and risk factors of hepatitis C virus genotype 1 infection: a national epidemiological survey of Chinese Han population

OBJECTIVE: Hepatitis C virus (HCV) infection is a high morbidity disease in China. The aim of this study was to explore the latest distribution of HCV genotypes in China, mainly focusing on epidemiological characteristics and risk factors of HCV genotype 1 in Chinese Han population.

PATIENTS AND METHODS: 793 HCV-positive patients were enrolled from 21 hospitals across China. The association of epidemiological data with HCV genotype 1 and the potential risk factors was analyzed using univariate and multivariate logistic regression analysis.

RESULTS: The HCV genotype 1b was detected in 66.9% of 793 patients. The way of infection, disease course, HCV RNA level, history of blood transfusion and smoking were found to be significantly different between patients infected with HCV genotype 1 and non-genotype 1. The result of univariate logistic regression analysis showed that HCV genotype 1 infection has a close relationship with age, gender, smoking history, the way of infection, allergy, disease course, and HCV RNA level. Moreover, the HCV RNA level, disease course, and blood transfusion history were the related risk factors for infection of HCV genotype 1 as demonstrated by multivariate logistic regression analysis.

CONCLUSIONS: The HCV genotype 1 was still the main genotype of HCV infection in China. We should intensify HCV screening for those people who aged over 50 years and had a history of blood transfusion in China. The treatment of genotype 1 should be paid more attention in antiviral of HCV.

L'articolo Epidemiological characteristics and risk factors of hepatitis C virus genotype 1 infection: a national epidemiological survey of Chinese Han population sembra essere il primo su European Review.

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Migration-related tuberculosis: epidemiology and characteristics of tuberculosis cases originating outside the European Union and European Economic Area, 2007 to 2013

Migrants arriving from high tuberculosis (TB)-incidence countries may pose a significant challenge to TB control programmes in the host country. TB surveillance data for 2007-2013 submitted to the European Surveillance System were analysed. Notified TB cases were stratified by origin and reporting country. The contribution of migrant TB cases to the TB epidemiology in EU/EEA countries was analysed. Migrant TB cases accounted for 17.4% (n?=?92,039) of all TB cases reported in the EU/EEA in 2007-2013, continuously increasing from 13.6% in 2007 to 21.8% in 2013. Of 91,925 migrant cases with known country of origin, 29.3% were from the Eastern Mediterranean, 23.0% from south-east Asia, 21.4% from Africa, 13.4% from the World Health Organization European Region (excluding EU/EEA), and 12.9% from other regions. Of 46,499 migrant cases with known drug-susceptibility test results, 2.9% had multidrug-resistant TB, mainly (51.7%) originating from the European Region. The increasing contribution of TB in migrants from outside the EU/EEA to the TB burden in the EU/EEA is mainly due to a decrease in native TB cases. Especially in countries with a high proportion of TB cases in non-EU/EEA migrants, targeted prevention and control initiatives may be needed to progress towards TB elimination.

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Increased incidence of invasive meningococcal disease of serogroup C / clonal complex 11, Tuscany, Italy, 2015 to 2016

We report an increase of serogroup C Neisseria meningitidis invasive meningococcal disease in Tuscany. From January 2015 to end February 2016, 43 cases were reported, among which 10 were fatal, compared to two cases caused by serogroup C recorded in 2014 and three in 2013. No secondary cases occurred. Thirty-five strains belonged to C:P1.5-1,10-8:F3-6:ST-11(cc11). Control measures have been adopted and immunisation campaigns implemented. Studies on risk factors and carriage are ongoing.

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The effect of migration within the European Union/European Economic Area on the distribution of tuberculosis, 2007 to 2013

Immigration from tuberculosis (TB) high-incidence countries is known to contribute notably to the TB burden in low-incidence countries. However, the effect of migration enabled by the free movement of persons within the European Union (EU)/European Economic Area (EEA) on TB notification has not been analysed. We analysed TB surveillance data from 29 EU/EEA countries submitted for the years 2007-2013 to The European Surveillance System. We used place of birth and nationality as proxy indicators for native, other EU/EEA and non-EU/EEA origin of the TB cases and analysed the characteristics of the subgroups by origin. From 2007-2013, a total of 527,467 TB cases were reported, of which 129,781 (24.6%) were of foreign origin including 12,566 (2.4%) originating from EU/EEA countries other than the reporting country. The countries reporting most TB cases originating from other EU/EEA countries were Germany and Italy, and the largest proportion of TB cases in individuals came from Poland (n=1,562) and Romania (n=6,285). At EU/EEA level only a small proportion of foreign TB cases originated from other EU/EEA countries, however, the uneven distribution of this presumed importation may pose a challenge to TB programmes in some countries.

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Presentation with gastrointestinal symptoms and high case fatality associated with group W meningococcal disease (MenW) in teenagers, England, July 2015 to January 2016

Atypical clinical presentations associated with group W meningococcal disease (MenW) are well-described and include pneumonia, septic arthritis, endocarditis and epiglottitis/supraglottitis. Following anecdotal reports of teenagers presenting with predominantly gastrointestinal symptoms, we undertook a case review of MenW cases in 15 to 19 year-olds diagnosed in England between July 2015 and January 2016. Of the 15 cases, seven presented with a short history of nausea, vomiting and diarrhoea; five of these seven cases died within 24 hours of presentation to hospital.

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WHO publishes an implementation framework on active tuberculosis drug-safety monitoring and management (aDSM)

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Diagnostic Utility of Neuregulin for Acute Coronary Syndrome

The purpose of this study was to determine the diagnostic test characteristics of serum neuregulin-1β (NRG-1β) for the detection of acute coronary syndrome (ACS). We recruited emergency department patients presenting with signs and symptoms prompting an evaluation for ACS. Serum troponin and neuregulin-1β levels were compared between those who had a final discharge diagnosis of myocardial infarction (STEMI and NSTEMI) and those who did not, as well as those who more broadly had a final discharge diagnosis of ACS (STEMI, NSTEMI, and unstable angina). Of 319 study participants, 11% had evidence of myocardial infarction, and 19.7% had a final diagnosis of ACS. Patients with MI had median neuregulin levels of 0.16 ng/mL (IQR [0.16–24.54]). Compared to the median of those without MI, 1.46 ng/mL (IQR [0.16–15.02]), there was no significant difference in the distribution of results (). Median neuregulin levels for patients with ACS were 0.65 ng/mL (IQR [0.16–24.54]). There was no statistical significance compared to those without ACS who had a median of 1.40 ng/mL (IQR [0.16–14.19]) (). Neuregulin did not perform successfully as a biomarker for acute MI or ACS in the emergency department.

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MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition

OBJECTIVE: Down-regulation of miR-138 is observed in a variety of cancers, which suggests that miR-138 may be involved in cancer pathogenesis. Our current work aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human NSCLC cells.

MATERIALS AND METHODS: Cell proliferation was determined by MTT assay. Real-time PCR and western blot were performed to detect the mRNA and protein expression levels. The target of miR-138 was validated by luciferase activity assay.

RESULTS: Compared with the chemosensitive parental cells, miR-138 was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition, the epithelial-mesenchymal transition (EMT) related markers E-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2 (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that ZEB2 was a direct target of miR-138.

CONCLUSIONS: Our study demonstrates that miR-138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a potential therapeutic target for drug-resistant NSCLC patients.

L'articolo MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition sembra essere il primo su European Review.

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Silencing of NUF2 inhibits proliferation of human osteosarcoma Saos-2 cells

OBJECTIVE: NUF2 (NUF2, Ndc80 kinetochore complex component), which is essential for kinetochore-microtubule attachment in mitosis, has emerged as a critical mediator of the cell cycle in multiple tumour occurrences. In the present study, we aimed to investigate the role of NUF2 in osteosarcoma, one of the most common primary bone tumours in children and young adults.

MATERIALS AND METHODS: Lentivirus-mediated short-hairpin RNA (shRNA) targeting NUF2 (Lv-shNUF2) was employed for evaluation in human osteosarcoma Saos-2 cells. After NUF2 silencing, the proliferation of Saos-2 cells was significantly inhibited, as determined by the MTT assay.

RESULTS: The colony forming ability was also significantly decreased in Saos-2 cells infected with Lv-shNUF2. Flow cytometry revealed that downregulation of NUF2 in Saos-2 cells caused a remarkable accumulation of the cell population in the S phase. Furthermore, the expression levels of cell cycle regulators cyclin A and cyclin-dependent kinase 2 (CDK2) were notably decreased, whereas those of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, were increased in response to NUF2 knockdown in Saos-2 cells.

CONCLUSIONS: Our findings suggest that NUF2 might modulate cell proliferation via cell cycle control in Saos-2 cells. Downregulation of NUF2 by shRNA might be a novel strategy for early treatment of osteosarcoma using molecular-targeting therapy.

L'articolo Silencing of NUF2 inhibits proliferation of human osteosarcoma Saos-2 cells sembra essere il primo su European Review.

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Advance in the study on p38 MAPK mediated drug resistance in leukemia

Leukemia is a group of malignant clone diseases of hematopoietic stem cells, while drug resistance (DR) has become the primary cause of chemotherapy failure. p38 mitogen-activated protein kinase (p38MAPK) signaling pathway induces cell activation, proliferation and apoptosis in response to extracellular stimuli. Recent studies have shown that p38 MAPK signaling pathway is closely associated with DR in leukemia. The present article reviews the relationship between p38 MAPK signaling pathway and DR in leukemia.

L'articolo Advance in the study on p38 MAPK mediated drug resistance in leukemia sembra essere il primo su European Review.

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PRAME promotes in vitro leukemia cells death by regulating S100A4/p53signaling

OBJECTIVE: PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME is expressed in a wide variety of tumors, but in contrast with most other tumor-associated antigens, it is also expressed in leukemias. The physiologic role of PRAME remains elusive. Recently, it has found PRAME could be involved in the regulation of cell death in leukemias, but the mechanism of the function is unclear. Here, we confirm that PRAME induces leukemias cell death by regulation of S100A4/p53 signaling.

MATERIALS AND METHODS: The pCDNA3-PRAME plasmid and its control were transfected with the KG-1 cells. The pCDNA3-PRAME transfected KG-1 cells were then transiently transfected with S100A4 cDNA or wt-p53 siRNA. The PRAME siRNA and its control were transfected with the K562 cells. The PRAME siRNA transfected K562 cells were then transiently transfected with S100A4 siRNA or pGMp53-Lu. PRAME, S100A4 and P53 were detected by Western blot assay in different time point. Annexin V/propidium iodide and MTT methods were used to detect apoptosis and cell survival rate.

RESULTS: KG-1 cells overexpressing the PRAME gene significantly induces apoptosis and decreases proliferation in vitro, followed by down-regulation of S100A4 and up-regulation of p53. Up-regulation of S100A4 by S100A4 transfection inhibits PRAME-induced p53 up-regulation. Furthermore, up-regulation of S100A4 by S100A4 transfection or down-regulation of p53 by p53 siRNA transfection reduces apoptosis and increases proliferation in vitro. Knockdown of PRAME in K562 cells significantly increases proliferation in vitro, followed by up-regulation of S100A4 and down-regulation of p53. The downregulation of S100A4 by S100A4 siRNA transfection increased p53 expression. Furthermore, downregulation of S100A4 by S100A4 siRNA transfection or up-regulation of p53 by p53 transfection decreases proliferation in vitro.

CONCLUSIONS: Our results suggest that the leukemias expressing high levels of PRAME has a favorable prognosis. PRAME promotes in vitro leukemia cells death by regulating S100A4/p53 signaling.

L'articolo PRAME promotes in vitro leukemia cells death by regulating S100A4/p53signaling sembra essere il primo su European Review.

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Prioritization of high-cost new drugs for HCV: how much is ethical sustainability?

Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease.
In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term "distributive justice" and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the price of new DAA will be reduced through competition and eventual patent expiration, the phenomenon of high drug costs will go on in the next decades and we need adequate tools to face the problems of distributive justice that come with it.

L'articolo Prioritization of high-cost new drugs for HCV: how much is ethical sustainability? sembra essere il primo su European Review.

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Quantitative fibrosis parameters highly predict esophageal-gastro varices in primary biliary cirrhosis

OBJECTIVE: Esophageal-gastro Varices (EGV) may develop in any histological stages of primary biliary cirrhosis (PBC). We aim to establish and validate quantitative fibrosis (qFibrosis) parameters in portal, septal and fibrillar areas as ideal predictors of EGV in PBC patients.PATIENTS AND METHODS: PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis.

PATIENTS AND METHODS: PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis.

RESULTS: Among the forty-nine PBC patients with qFibrosis images, twenty-nine PBC patients with both esophagogastroscopy data and qFibrosis data were selected out for EGV prognosis analysis and 44.8% (13/29) of them had EGV. The qFibrosis parameters of collagen percentage and number of crosslink in fibrillar area, short/long/thin strings number and length/width of the strings in septa area were associated with EGV (p < 0.05). Multivariate logistic analysis showed that the collagen percentage in fibrillar area ≥ 3.6% was an independent factor to predict EGV (odds ratio 6.9; 95% confidence interval 1.6-27.4). The area under receiver operating characteristic (ROC), diagnostic sensitivity and specificity was 0.9, 100% and 75% respectively.CONCLUSIONS: Collagen percentage in

CONCLUSIONS: Collagen percentage in the fibrillar area as an independent predictor can highly predict EGV in PBC patients.

L'articolo Quantitative fibrosis parameters highly predict esophageal-gastro varices in primary biliary cirrhosis sembra essere il primo su European Review.

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Characteristic analysis of white matter lesions in migraine patients with MRI

OBJECTIVE: The aim of this study is to analyze the characteristics of white matter lesions in abnormal manifestations of magnetic resonance imaging (MRI) of patients with migraine, and its relationship with migraine.

PATIENTS AND METHODS: 38 patients, diagnosed with migraine were continuously selected as the observation group, while during the same period, 30 healthy individuals were selected as the control group. The differences of the features of MRI of two groups, the ratios of white matter lesions manifestations and the severity were compared.

RESULTS: The manifestations of MRI in patients with migraine were mainly white matter lesions. The accuracy rate was 86.7%, and the sensibility was 92.3%. According to Wahlund white matter lesions classifications, patients with migraine were mainly Level II and Level III (84.2%). It can be acquired from relevant analyses that white matter lesions classifications and the degrees of migraine were positively correlated (p < 0.05). White matter lesions were mainly distributed in the frontal lobe (78.9%), limbic system (60.5%) and parietal lobe (28.9%).

CONCLUSIONS: The MRI of migraine, the manifestations of white matter lesions were relatively sensitive. The higher the classification was linked with the degree of migraine. They were mainly distributed in the frontal lobe, limbic system and parietal lobe.

L'articolo Characteristic analysis of white matter lesions in migraine patients with MRI sembra essere il primo su European Review.

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Nesfatin-1 hormone levels in morbidly obese patients after laparoscopic sleeve gastrectomy

OBJECTIVE: To investigate changes in body mass index (BMI) and nesfatin-1 levels in patients with morbid obesity who had undergone laparoscopic sleeve gastrectomy (LSG).PATIENTS AND METHODS: Blood samples were collected from, and the BMI calculated of 30 morbidly obese patients pre-surgery and at 3 and 6 months post-surgery. Nesfatin-1 hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Descriptive statistical analysis of the data was performed using Kruskal-Wallis variance analysis, one-way ANOVA, and the Bonferroni-Dunn test. The correlations between continuous variables not displaying normal distribution and those displaying normal distributions were analyzed using the Spearman correlation test and the Pearson correlation test, respectively.

PATIENTS AND METHODS: Blood samples were collected from, and the BMI calculated of 30 morbidly obese patients pre-surgery and at 3 and 6 months post-surgery. Nesfatin-1 hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Descriptive statistical analysis of the data was performed using Kruskal-Wallis variance analysis, one-way ANOVA, and the Bonferroni-Dunn test. The correlations between continuous variables not displaying normal distribution and those displaying normal distributions were analyzed using the Spearman correlation test and the Pearson correlation test, respectively.RESULTS: The mean age of the 30 patients was 41.23 ± 10.37 years. The mean BMI values (kg/m2) were 49.30 ± 7.92, 39,48 ± 7.32, and 34.39 ± 7.56 presurgery, three months

RESULTS: The mean age of the 30 patients was 41.23 ± 10.37 years. The mean BMI values (kg/m2) were 49.30 ± 7.92, 39,48 ± 7.32, and 34.39 ± 7.56 presurgery, three months post-surgery, and six months post-surgery, respectively (p < 0.001). Mean nesfatin-1 levels (ng/ml) were 22.80 ± 14.16, 60.23 ± 52.92, and 96.99 ± 40.20 presurgery, three months post-surgery, and six months post-surgery, respectively (p < 0.001). The postoperative months 3 and 6 BMI values were significantly lower than the preoperative BMI value and the postoperative month 6 BMI value was significantly lower than the postoperative month 3 BMI value (p < 0.001). The postoperative months 3 and 6 nesfatin-1 levels were significantly lower than the preoperative nesfatin-1 levels. A negative correlation was found between age and preoperative nesfatin-1 values (p = 0.001, r = -0.0557).

CONCLUSIONS: Observation of significant increases in nesfatin-1 hormone levels in morbidly obese patients who had undergone LSG indicate that nesfatin-1 has important anorexigenic effects post-surgery and may be an important component of future obesity treatments.

L'articolo Nesfatin-1 hormone levels in morbidly obese patients after laparoscopic sleeve gastrectomy sembra essere il primo su European Review.

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The association of vascular endothelial growth factor, metalloproteinases and their tissue inhibitors with cardiovascular risk factors in the metabolic syndrome

OBJECTIVE: The present study was proposed to examine the matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor (VEGF) in patients with metabolic syndrome (MetS), and to compare these parameters with healthy controls. We also compared the possible association of the circulating levels of MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF with cardiovascular risk factors in patients with MetS. We also compared the possible association of the circulating levels of MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF with cardiovascular risk factors in patients with MetS.

PATIENTS AND METHODS: A total of 45 patients with MetS and 17 healthy controls with a body mass index (BMI) less than 25 kg/m2 were enrolled in the study. Plasma MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF levels were determined using ELISA.

RESULTS: TIMP-1,-2, MMP-2,-9 levels and intima-media thickness (IMT) were significantly higher in patients with MetS compared with healthy controls (p<0.001). Serum VEGF levels were found to be significantly increased (p<0.05) in MetS compared with healthy controls. MMP-2 was positively correlated with TIMP-1 (r=0.357; p<0.05) and TIMP-2 (r=0.320; p<0.05) in MetS patients. MMP-2 was positively correlated with IMT (r=0.39; p<0.01). According to the ROC curves, TIMP-1 levels were both sensitive (93.3%) and specific (81.2%).

CONCLUSIONS: We observed that the patients with MetS have increased circulating concentrations of MMP-9, MMP-2, and TIMP-1, TIMP-2 that are associated with increased concentrations of VEGF. These findings suggest that MMP-2 may have a role in the increased cardiovascular risk of MetS patients.

L'articolo The association of vascular endothelial growth factor, metalloproteinases and their tissue inhibitors with cardiovascular risk factors in the metabolic syndrome sembra essere il primo su European Review.

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Polymers, Vol. 8, Pages 91: Drug Delivery Systems Obtained from Silica Based Organic-Inorganic Hybrids

This is a review of hybrid materials based on silica as an inorganic phase used as drug delivery systems (DDS). Silica based DDS have shown effectivity when compared with traditional delivery systems. They present advantages such as: (a) ability to maintain the therapeutic range with minor variations; (b) prevention of local and systemic toxic effects; (c) plasma concentrations increase of substances with a short half-life; and (d) reduction of the number of daily doses, which may increase patient adherence to the treatment. These advantages occur due to the physical, chemical and optical properties of these materials. Therefore, we discuss the properties and characteristics of them and we present some applications, using different approaches of DDS to ensure therapeutic effectiveness and side effects reduction such as implantable biomaterial, film-forming materials, stimuli-responsive systems and others.

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