Ιατρικά Άρθρα: 09/04/17

Publication date: Available online 5 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Maiada M. Sadek, Mina Barzegar Amiri Olia, Cameron J. Nowell, Νicholas Barlow, Carl H. Schiesser, Sandra.E. Nicholson, Raymond S. Norton
Nitric oxide (NO) is an important effector molecule in host defence against bacterial pathogens. The development of fluorescence imaging to monitor NO production in vitro and in vivo will increase our understanding of its biological role. Recently, a novel "trappable" fluorescent blue 'turn-on' Cu(II)-complexed coumarin-based probe (CB) has been developed to detect NO. In this study, CB was investigated to evaluate its ability to detect NO in macrophages. Using confocal microscopy, NO was successfully detected in macrophages in the presence of stimuli that induce nitric oxide synthase (iNOS), the enzyme responsible for production of NO. The time dependence and subcellular compartmentalisation of CB in macrophages were evaluated. The probe can be trapped within cells and reacts directly and specifically with NO, rendering it a promising tool for imaging NO in response to pharmacological agents that modulate its level, for example during bacterial infections.

Graphical abstract

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3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

Publication date: Available online 4 September 2017
Source:Dental Materials
Author(s): F. Fahimipour, M. Rasoulianboroujeni, E. Dashtimoghadam, K. Khoshroo, M. Tahriri, F. Bastami, D. Lobner, L. Tayebi
ObjectiveVascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineering methods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model.MethodsThe paste, composed of (VEGF-loaded PLGA)-containing gelatin/alginate/β-TCP in water, was loaded into standard Nordson cartridges and promptly employed for printing the scaffolds. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink at room temperature.ResultsThe in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98±11MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture.SignificanceThe 3D printed gelatin/alginate/β-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects.

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Re: “Ultrasound Findings on Hands and Wrists of Patients with Systemic Lupus Erythematosus: Relationship with Physical Examination”

Publication date: Available online 4 September 2017
Source:Ultrasound in Medicine & Biology
Author(s): Matteo Piga, Alessandra Gabba, Alessandro Mathieu, Alberto Cauli

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Role of Densitometric Criteria in Evaluation of Effectiveness of Antiangiogenic Therapies in Metastatic Colorectal Cancer: An Italian Clinical Experience

Background/Aim: To evaluate the role of densitometric criterion using the Choi Criteria in the assessment of the response to antiangiogenic treatments of metastatic colorectal cancer (mCRC) compared to the RECIST criteria. Patients and Methods: Fifty-four patients (mean age=50.6 years) affected by advanced colorectal cancer and with hepatic and possibly peritoneal and pulmonary metastases, that can be treated with bevacizumab, were prospectively evaluated by computerized tomography (CT) scan. Metastases were also evaluated by CT in one-dimensional form according to RECIST. Results: Results show that in 58% of analyzed cases, stable disease according to RECIST coincided with stable disease according to the CHOI criteria, whereas in 42% of analyzed cases disease progression according to RECIST corresponded to stable disease or even partial response according to CHOI criteria. Conclusion: By using the densitometric criterion with CHOI criteria, the evaluation of the response to antiangiogenic treatment of mCRC is partially different compared to RECIST criteria.

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Lidocaine Stimulates the Function of Natural Killer Cells in Different Experimental Settings

Background: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery. Materials and Methods: NK cells from healthy donors and 43 patients who had undergone surgery for cancer were isolated. The function of NK cells was measured by lactate dehydrogenase release assay. NK cells were incubated with clinically relevant concentrations of lidocaine. By flow cytometry, we determined the impact of lidocaine on the expression of galactosylgalactosylxylosylprotein3-beta-glucuronosytranferase 1, marker of cell maturation (CD57), killer cell lectin like receptor A, inhibitory (NKG2A) receptors and killer cell lectin like receptor D, activation (NKG2D) receptors of NK cells. Differences in expression at p<0.05 were considered statistically significant. Results: Lidocaine increased the expression of NKG2D receptors and stimulated the function of NK cells against ovarian, pancreatic and ovarian cancer cell lines. Lidocaine also increased the cytolytic activity of NK cells from patients who underwent oncological surgery, except for those who had orthopedic procedures. Conclusion: Lidocaine showed an important stimulatory activity on NK cells. Our findings suggest that lidocaine might be used perioperatively to minimize the impact of surgery on NK cells.

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MRI and Ultrasound Fusion Imaging for Cervical Cancer

Background: Evaluating locoregional extension of cervical cancer is a key step in patient management. This study evaluated the feasibility of fusion imaging – a combination of magnetic resonance imaging (MRI) with real-time high-resolution ultrasound (US) – to diagnose cervical cancer and its extension. Patients and Methods: This prospective bi-center study included 13 women who underwent a 1.5-T MRI protocol including at least one T2-weighted plane. The results of imaging fusion were then compared with US and MRI results alone. Results: Cervical cancer was detected as a hyperechogenic hypervascularized lesion. Parametrial extension was detected by exploration of the stromal ring and the use of color Doppler mode in fusion imaging, and characterized by visualization of a vascular bridge. Conclusion: Fusion imaging could be used as a complementary technique for MRI to enhance diagnostic performance for cervical cancer lesions. While MRI remains the reference, real-time fusion imaging could improve its characterization and detect parametrial infiltration.

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Physical Needs of Long-term Cancer Patients

The enormous success in the therapeutic area of oncology has allowed achieving a number of long-term survival patients unthinkable until a few decades ago. The number of cancer survivors in the world has, in fact, almost tripled in the last decade alone. Anticancer therapies, including those of the latest generation, aimed at targeting also the chronicity of the disease, are not free from side-effects, especially when used in the long term. This scenario should lead to development of follow-up programs with the purpose of assessing long-term effects related to cancer treatments, in addition to the early detection of any relapse or a second tumor. Oncologists who take care of cancer survivors cannot ignore these effects; it is, therefore, essential to start a program of prevention and treatment of these sequelae, to meet patients' health needs.

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Study on the Validity of Pancreaticoduodenectomy in the Elderly

Aim: Pancreaticoduodenectomy (PD) is still the only curative treatment for periampullary cancer. Confirming the outcomes of PD in elderly patients is important as the aging population continues to grow. Patients and Methods: We analyzed 340 patients with periampullary cancer who underwent PD, dividing them into three groups by age: group A: aged 64 years or younger, n=115; group B: 65-74 years, n=144; and group C: 75 years or older, n=81. Results: Group C had a significantly higher 60-day mortality of 6.3% (p=0.04), the lowest 5-year overall survival rate of 9.9% (p=0.02), and there was no impact of staging of the Union for International Cancer Control classification on overall survival of patients with pancreatic cancer. Independent prognostic factors of group C in the multivariate analysis were pancreatic cancer and reoperation. Conclusion: For elderly patients aged 75 years or over, caution should be exercised in selecting PD for patients with pancreatic cancer.

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Deepening a Simple Question: Can MSCs Be Used to Treat Cancer?

In cancer, mesenchymal stem/stromal cells (MSCs) have been considered as vehicles for targeted delivery of drugs due to their inherent tropism toward primary and metastatic tumors. However, it is still unclear whether MSCs could be therapeutically explored without significant harm, since a great amound of evidence indicates that MSCs are able to exert both tumor-suppressive and pro-oncogenic effects. Here, we discuss how MSCs might adopt a pro- or anti-inflammatory profile in response to changes within the tumor microenvironment and how these features may lead to opposite outcomes in tumor development. Additionally, we address how differences in experimental design might impact interpretation and consistency of the current literature in this specific field. Finally, we point-out critical issues to be addressed at a pre-clinical stage, regarding safety and therapeutic effectiveness of MSCs application in cancer treatment.

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Flattening Filter Free vs. Flattened Beams for Lung Stereotactic Body Radiation Therapy

Background/Aim: To assess the clinical impact of high dose rate stereotactic body radiation therapy (SBRT) in patients with lung neoplastic lesions. Patients and Methods: From January 2014 to June 2016, a single-center retrospective analysis was performed including all patients treated by either flattening filter free (FFF) beams or flattening filter beams (FF) three-dimensional (3D) SBRT for lung neoplastic lesions. Results: A total of 99 SBRT were performed on 75 patients. Among these, 29 SBRT were performed using a FFF technique while 70 other SBRT were done using a FF technique. Median follow-up time was 12.9 months. Overall, no difference between the two groups was found except for the mean beam on time which was reduced by 3.3 to 0.9 minutes in the FFF group (p<0.001). Conclusion: We report a low toxicity rate and a shortened beam on time in patients treated with 3D FFF SBRT for lung neoplastic lesions.

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Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models.

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The Local Recurrence of Breast Cancer with Squamous Metaplasia and Obvious Histological Heterogeneity

Case Report: We herein report a case of local recurrence of breast cancer with squamous metaplasia and obvious intratumoral and intertumoral heterogeneity. A 39-year-old female patient was diagnosed with T3N2M0 stage IIIB right breast cancer and underwent right total mastectomy and axillar lymph node dissection. At four years after surgery, she became aware of chest wall pain and diagnostic imaging revealed recurrence in the lung, right thoracic wall and sternum. The recurrent lesions remained stable for 18 months with endocrine therapy. Thereafter, the lesion in the right thoracic wall suddenly became enlarged. Moreover, liver metastasis was confirmed on FDG-PET/CT. She underwent right thoracic wall tumor resection. A biopsy was simultaneously performed to obtain a specimen from the site of liver metastasis. Postoperatively, the right chest wall mass showed obvious intratumoral heterogeneity; squamous differentiation with aggressive features and a papillotubular component similar to the primary tumor. The metastatic liver tumor showed similar pathological features to the primary tumor. Conclusion: Intratumoral and intertumoral heterogeneity within primary tumors and associated metastatic sites may contribute to treatment failure and drug resistance.

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Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

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Thrombocytosis Portends Adverse Prognosis in Colorectal Cancer: A Meta-Analysis of 5,619 Patients in 16 Individual Studies

Aim: The current study aimed to determine the prognostic significance of thrombocytosis in patients with colorectal cancer (CRC) by a meta-analysis of the literature. Patients and Methods: The meta-analysis followed the 2009 guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic literature review was conducted from PubMed and Web of Science for articles published up to May 15, 2015. Sixteen studies with a total of 5,619 patients met the inclusion criteria. Hazard ratios and 95% confidence intervals were retrieved from the original articles, calculated from the published Kaplan–Meier survival curves, or the corresponding authors were contacted for additional information. Heterogeneity was assessed using the I² statistic and Chi-square tests. Publication bias was assessed by Begg's funnel plot, Egger's linear regression test and trim-and-fill method. Sensitivity analysis was performed to validate the reliability. Results: Thrombocytosis is associated with shorter overall, disease-free and cancer-specific survival. Overall survival is reduced in patients with thrombocytosis regardless of their clinical tumor stage, and ethnicity. Shortened disease-free survival is associated with elevated platelet count in the non-specific stage (I-IV), localized tumor (stage I-III), and in the Asian patient population. Thrombocytosis is further associated with reduced cancer-specific survival in the non-specific stage and in Asian patients. Finally, thrombocytosis is significantly related to female patients, colon tumor location, T3-4 stage, lymph node positivity, metastasis, undifferentiated histology and lymphatic involvement. Conclusion: Thrombocytosis portends adverse prognosis in CRC, and may serve as a clinically useful marker to facilitate risk stratification and guide postoperative management.

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Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with EGFR Mutations at a High Cell Density

Background/Aim: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. Materials and Methods: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities. Results: The 3D cell culture experiments showed the enhanced mitochondrial biological activity in clustered cell culture treated with gefitinib. Interestingly, the expression levels of Bcl-x_L and Bax, were affected by the cellular number and gefitinib treatment. We also found that gefitinib prevented additive anticancer activity in the combinational treatment with doxorubicin, which induces mitochondria-dependent apoptotic cell death. Conclusion: Our results indicate that gefitinib may work as a mitochondrial protector against combinational treatment with mitochondria-dependent anticancer agents in high-cell-density.

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Metastatic Microcystic Adnexal Carcinoma with DNA Sequencing Results and Response to Systemic Antineoplastic Chemotherapy

Microcystic adnexal carcinoma (MAC) is a rare cutaneous malignancy. Due to its rarity, the molecular characteristics and treatment for metastatic MAC remain undefined. Here we present, as far as we are aware, the first case of metastatic MAC with DNA sequencing results indicating a mutation in TP53 and chromosomal losses in cyclin dependent kinase inhibitor 2A (CDKN2A) and cyclin dependent kinase inhibitor 2B (CDKN2B). In addition, this is the first case of metastatic MAC with a documented objective response to systemic antineoplastic chemotherapy (carboplatin and paclitaxel) confirmed by positron emission tomography/computed tomography. Our case increases the very limited medical knowledge of this rare disease.

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Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells

Background: Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Materials and Methods: Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Results: Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Conclusion: Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application.

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Prognostic Significance of Serum CEA for Non-small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy

Background/Aim: To examine the prognostic significance of serum carcinoembryonic antigen (CEA) for stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients and Methods: In total, 129 stage I NSCLC patients were analyzed and divided into two groups: CEA-High (CEA>5 ng/ml) and CEA-Low (CEA≤5 ng/ml). Results: Median follow-up time was 38 months. Overall survival was not significantly different between CEA-High (n=47) and CEA-Low (n=82) patients (57% vs. 63% at 3 years; p=0.39), although progression-free survival (PFS) was significantly worse in CEA-High patients (31% vs. 51% at 3 years; p=0.01). Larger tumor size and high CEA level were independent prognostic factors for worse PFS. Failure pattern analysis showed that regional node or distant recurrence was more common in CEA-High patients (47%) than in CEA-Low patients (29%). Conclusion: Patients with CEA-High stage I NSCLC have a higher risk of regional or systemic relapse and should be followed-up carefully.

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Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2

Background: Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). Materials and Methods: We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2. Results: ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity. Conclusion: We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer.

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Comparing the Efficacy of DeVIC Therapy and High-dose Methotrexate Monotherapy with Whole-brain Radiation Therapy for Newly-diagnosed Primary Central Nervous System Lymphoma: A Single Institution Study

Background/Aim: In the current study, we aimed to compare DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy with high-dose methotrexate (HD-MTX) monotherapy plus whole-brain radiation therapy (WBRT) for newly-diagnosed primary central nervous system lymphoma (PCNSL), in terms of their efficacies and tolerability. Patients and Methods: A total of 21 consecutive patients with PCNSL were treated with DeVIC therapy and WBRT, between 2002 and 2010. From 2010 to 2014, 14 consecutive patients with PCNSL were treated with HD-MTX followed by WBRT. Results: Overall response rates of complete and partial response for initial chemotherapy were significantly better with DeVIC therapy (95.2%) than with HD-MTX monotherapy (50%). Furthermore, one-year and two-year progression-free survival (PFS) rates were better in the DeVIC cohort than in the HD-MTX cohort. DeVIC therapy yielded higher early response rates, longer PFS, and manageable adverse events, and may be potentially better for the treatment of cases that are refractory to MTX-based therapy. Conclusion: Our retrospective clinical study revealed that DeVIC therapy is comparable with that of HD-MTX monotherapy plus WBRT, for newly diagnosed PCNSL.

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Effective Metabolic Targeting of Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models with Recombinant Methioninase

Background: Methionine dependence may be the only known general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino--mercaptomethane lyase [EC 4.4.1.11]) (recombinant methioninase [rMETase]), which was subsequently tested in mouse models of various types of human tumors. The present study aimed to investigate the efficacy of rMETase on human osteosarcoma cells in vitro and in vivo. Materials and Methods: Human osteosarcoma cell lines 143B, HOS and SOSN2 were tested in vitro for survival during a 72-h exposure to rMETase using the WST-8 assay. Half-maximal inhibitory concentrations were calculated for in vitro efficacy experiments. 143B cells were orthotopically transplanted into the tibia of nude mice. Mouse models were randomized into the following groups 1 week after transplantation: Group 1, untreated control; Group 2, cisplatinum (CDDP) [intraperitoneal (i.p.) injection at 6 mg/kg weekly, for 3 weeks], positive control; Group 3, rMETase, 100 units/mouse i.p. daily, for 21 days. Tumor sizes and body weight were measured with calipers and a digital balance once per week, respectively. Results: rMETase significantly inhibited osteosarcoma cell growth, in a dose-dependent manner, in vitro. Both CDDP and rMETase treatment significantly inhibited tumor volume compared to untreated control mice at 5 weeks after initiation. Tumor volumes were as follows: Group 1, untreated, control: 1808.2 ± 344 mm³; Group 2, CDDP: 1102.2 ± 316 mm³, p=0.0008 compared to untreated control; Group 3, rMETase: 884.8 ± 361 mm³, p=0.0001 compared to untreated control. There were no animal deaths in any group. The body weight of mice was not significantly different between any group. Conclusion: rMETase showed promising efficacy against osteosarcoma, a recalcitrant tumor type. Future studies will investigate the efficacy of rMETase on patient-derived orthotopic xenograft (PDOX) models of osteosarcoma as a bridge to testing rMETase in the clinic.

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Surgical Strategy for T1 Duodenal or Ampullary Carcinoma According to the Depth of Tumor Invasion

Aim: To investigate the utility of local resection (LR) for T1 duodenal carcinoma and T1 ampullary carcinoma. Patients and Methods: Between June 2002 and November 2014, a total of 64 patients with pathological T1 (pT1) ampullary carcinoma (25 patients) and pT1 duodenal carcinoma (39 patients) were treated. Of these, 33 patients underwent local resection (LR group), while the other 31 patients underwent pancreatoduodenectomy (PD group). Results: The LR group had 31 patients with pT1a and 2 patients with pT1b. PD group had 18 patients with pT1a and 13 patients with pT1b. One patient with pT1b duodenal carcinoma (20.0%) and one patient with pT1b ampullary carcinoma (10.0%) developed lymph node metastasis, while none of the patients with pT1a disease developed metastases. Conclusion: LR may be considered in the patients preoperatively diagnosed with T1a duodenal carcinoma and T1a ampullary carcinoma.

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Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro

Background/Aim: Extracts of Paeonia suffruticosa are traditionally used in Chinese medicine to increase blood flow. Recently, this extract has been shown to possess anti-tumor and anti-inflammatory properties, though this mechanism remains unknown. In the current work, we prepared extracts of P. suffruticosa and analyzed their effects on MDA-MB-231 triple-negative breast cancer cells. Materials and Methods: Varying concentrations of an aqueous extract of P. suffruticosa was administered to MDA-MB-231. An MTS assay was used to determine the cell viability. Cytokine production was investigated through enzyme-linked immunosorbent assay (ELISA). Caspase-Glo assays were performed to measure caspase 3/7, 8 and 9 to analyze anti-apoptotic effects. Results: MTS assay for cell viability revealed that the extract increased viability at low concentrations (0.6 mg/ml) and decreased viability observed at concentrations ≥2.5 mg/ml (p<0.01). ELISA for IL-6, IL-2, and TNF-alpha revealed a biphasic dose-response inversely related to viability (p<0.05). IL-24 expression also increased at 2.5 mg/ml and 4.0 mg/ml (p<0.05). Bax levels remained relatively constant while Bcl-2 decreased significantly in all concentrations (p<0.01). Small decreases in Fas ligand levels was observed in parallel with a lack of increase in caspase-8 activity. Most notable was that while 4mg/ml of P. suffruticosa extract reduced MDA-MB-231 viability by >60% (p<0.01), the same concentration reduced the viability of non-transformed HaCat cells by ~8% (p>0.05), suggesting a selective oncolytic effect. Conclusion: P. suffruticosa extract has the ability to modulate the production of several tumor suppressive cytokines, induce intrinsic apoptosis and has the capability of reducing cancer burden while sparing healthy tissue.

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Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Karem H. Alzoubi, Fadia A. Mayyas, Rania Mahafzah, Omar F. Khabour
Consumption of high-fat diet (HFD) induces oxidative stress in the hippocampus that leads to memory impairment. Melatonin has antioxidant and neuroprotective effects. In this study, we hypothesized that chronic administration of melatonin can prevent memory impairment induced by consumption of HFD. Melatonin was administered to rats via oral gavage (100mg/kg/day) for 4 weeks. HFD was also instituted for the same duration. Behavioral studies were conducted to test spatial memory using the radial arm water maze. Additionally, oxidative stress biomarkers were assessed in the hippocampus. Results showed that HFD impaired both short- and long- term memory (P<0.05), while melatonin treatment prevented such effects. Furthermore, melatonin prevented HFD-induced reduction in levels of GSH, and ratio of GSH/GSSG, and increase in GSSG in the hippocampus. Melatonin also prevented reduction in the catalase activity in hippocampus of animals on HFD. In conclusion, HFD induced memory impairment and melatonin prevented this impairment probably by preventing alteration of oxidative stress in the hippocampus.

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Differential effects of imipramine and CORT 118335 (Glucocorticoid receptor modulator/mineralocorticoid receptor antagonist) on brain-endocrine stress responses and depression-like behavior in female rats

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Elizabeth T. Nguyen, Jody L. Caldwell, Joshua Streicher, Valentina Ghisays, Nikolaus J. Balmer, Christina M. Estrada, Matia B. Solomon
Depression is commonly associated with hypothalamic-pituitary adrenal (HPA) axis dysfunction that primarily manifests as aberrant glucocorticoid secretion. Glucocorticoids act on Type I mineralocorticoid (MR) and Type II glucocorticoid receptors (GR) to modulate mood and endocrine responses. Successful antidepressant treatment normalizes HPA axis function, in part due to modulatory effects on MR and GR in cortico-limbic structures. Although women are twice as likely to suffer from depression, little is known about how antidepressants modulate brain, endocrine, and behavioral stress responses in females. Here, we assessed the impact of CORT 118335 (GR modulator/MR antagonist) and imipramine (tricyclic antidepressant) on neuroendocrine and behavioral responses to restraint or forced swim stress (FST) in female rats (n=10–12/group). Increased immobility in the FST is purported to reflect passive coping or depression-like behavior. CORT 118335 dampened adrenocorticotropic hormone (ACTH) and corticosterone responses to the FST, but did not affect immobility. Imipramine suppressed ACTH, but had minimal effects on corticosterone responses to FST. Despite these marginal effects, imipramine decreased immobility, suggesting antidepressant efficacy. In an effort to link brain-endocrine responses with behavior, c-Fos was assessed in HPA axis and mood modulatory regions in response to the FST. CORT 118335 upregulated c-Fos expression in the paraventricular nucleus of the hypothalamus. Imipramine decreased c-Fos in the basolateral amygdala and hippocampus (CA1 and CA3), but increased c-Fos in the central amygdala. These data suggest the antidepressant-like (e.g., active coping) properties of imipramine may be due to widespread effects on cortico-limbic circuits that regulate emotional and cognitive processes.

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A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Sevda Gheibi, Khosrow Kashfi, Asghar Ghasemi
Prevalence of diabetes, a serious public health problem is rapidly increasing worldwide. Type-2 diabetes is the common form of diabetes characterized by insulin resistance and abnormalities in insulin production. Despite the current development of therapeutic agents, there is no effective treatment without side effects; it is therefore necessary to find new prevention strategies and better treatments. For this purpose animal models of diabetes are appropriate tools, of which rodents due to the short generation time and economic considerations are the first choice. The aim of this review is to present features of a frequently used model of type-2 diabetes in rat, induced by a high fat diet and streptozotocin, taking into account its advantages/disadvantages and presenting a practical guide.

Graphical abstract

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The anti-tumor effect of aspirin: What we know and what we expect

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Ji Ma, Zhonglin Cai, Hongliang Wei, Xinlan Liu, Qingli Zhao, Tao Zhang
Aspirin has been widely used as an antipyretic analgesic drug. More and more evidences have shown that aspirin may be play some role on anti-tumor. In this article, we reviewed the research history of aspirin in the treatment and prevention of cancer. Many epidemiological and clinical studies have shown that aspirin can reduce the risk of a variety of malignant tumors and reduce cancer mortality. In addition, we discuss the specific mechanisms of aspirin in the anti-tumor effects. It has been found that aspirin mainly depends on the COX pathway and non-COX pathway to inhibit tumor cell growth and to curb tumor development. In this article, clinical studies and anti-tumor mechanism studies published in recent years are reviewed.

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Exceptionally high UBE2C expression is a unique phenomenon in basal-like type breast cancer and is regulated by BRCA1

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Tao Qin, Gena Huang, Liyuan Chi, Silei Sui, Chen Song, Na Li, Siwen Sun, Ning Li, Min Zhang, Zuowei Zhao, Lianhong Li, Man Li
Ubiquitin-conjugating enzyme 2C (UBE2C) is overexpressed in various types of cancer, leading to poor outcomes and drug resistance. UBE2C may also have a critical role in phenotypes associated with poor prognosis in breast cancer; however, the relationship between UBE2C expression and clinical outcome in breast cancer subtypes has not previously been investigated. We firstly analyzed breast cancer patient data and immunohistochemistry of breast cancer patient samples. We demonstrated that UBE2C was associated with poor prognosis in breast cancer, particularly basal-like breast cancer, a subtype with aggressive clinical features. Interestingly, we found that there was a close relationship between the expression of BRCA1 and UBE2C in the MCF-7 and MDA-MB-231 breast cancer cell lines. Upregulation of BRCA1 could inhibit the expression of UBE2C. In cells with BRCA1 silenced down, expression of UBE2C was obviously increased, with a concurrent decrease in cellular sensitivity to doxorubicin. Suppression of UBE2C expression by RNA interference led to decrease the mRNA expressions of BCRP, MRP1 and P-gp in doxorubicin-treated MDA-MB-231 cells. Moreover, treatment with 1μg/ml doxorubicin led to increased expression of UBE2C. The results show high expression of UBE2C is a potential prognostic factor of poor outcome in basal-like breast cancer. Moreover, loss of BRCA1 function results in an increase in UBE2C expression and chemical resistance to doxorubicin in breast cancer cells.

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An interdisciplinary approach to the development of accessible computer-administered measurement instruments

Publication date: Available online 4 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Susan Magasi, Mark Harniss, Allen W. Heinemann
Principles of fairness in testing require that all test takers, including people with disabilities, have an equal opportunity to demonstrate their capacity in the construct being measured. Measurement design features and assessment protocols can pose barriers for people with disabilities. Fairness in testing is a fundamental validity issue at all phases in the design, administration and interpretation of measurement instruments in clinical practice and research. There is limited guidance for instrument developers in how to develop and evaluate the accessibility and usability of measurement instruments. This paper describes a 6-stage iterative process for developing accessible computer-administered measurement instruments based on our work in several major measurement initiatives. Interdisciplinary teams of accessibility experts, content and measurement experts, information technology experts and people with disabilities should work together to ensure that measurement instruments are accessible and usable by a wide range of users. The development of accessible measurement instruments is not only an ethical requirement, it also ensures better science by minimizing measurement bias, missing data, and attrition due to mismatches between the target population and test administration platform and protocols.

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Clinical benefits of joint mobilisation on ankle sprains: a systematic review and meta-analysis

Publication date: Available online 4 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ishanka Weerasekara, Peter Osmotherly, Suzanne Snodgrass, Jodie Marquez, Rutger de Zoete, Darren A. Rivett
ObjectiveTo assess the clinical benefits of joint mobilisation on ankle sprains.Data sourcesMEDLINE, MEDLINE In Process, Embase, AMED, PsycINFO, CINAHL, Cochrane library, PEDro, Scopus, SPORTDiscus and Dissertations and Thesis were searched from inception to June, 2017.Study SelectionStudies investigating humans with a grade I or II lateral or medial sprains of the ankle in any pathological state from acute to chronic, who had been treated with joint mobilisation were considered for inclusion. Any conservative intervention was considered as a comparator. Commonly reported clinical outcomes were considered such as ankle range of movement, pain, and function. After screening of 1530 abstracts, 56 studies were selected for full text screening, and 23 were eligible for inclusion. Eleven studies on chronic sprains reported sufficient data for meta-analysis.Data ExtractionData were extracted using the participants, interventions, comparison, outcomes and study design approach. Clinically relevant outcomes (dorsiflexion range, proprioception, balance, function, pain threshold, pain intensity) were assessed at immediate, short term and long term follow-up points.Data SynthesisMethodological quality was assessed independently by two reviewers and most studies were found to be of moderate quality, with no studies rated as poor.Meta-analysis revealed significant immediate benefits of joint mobilisation compared to comparators on improving postero-medial dynamic balance (p=0.0004), but not for improving dorsiflexion range (p= 0.16), static balance (p = 0.96) or pain intensity (p= 0.45). Joint mobilisation was beneficial in the short term for improving weight-bearing dorsiflexion range (p= 0.003) compared to a control.ConclusionJoint mobilisation appears to be beneficial for improving dynamic balance immediately after application and dorsiflexion range in the short term. Long term benefits have not been adequately investigated.

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Face perception in pure alexia: Complementary contributions of the left fusiform gyrus to facial identity and facial speech processing

Publication date: Available online 4 September 2017
Source:Cortex
Author(s): Andrea Albonico, Jason J.S. Barton
Recent concepts of cerebral visual processing predict from overlapping patterns of face and word activation in cortex that left fusiform lesions will not only cause pure alexia but also lead to mild impairments of face processing.Our goal was to determine if alexic subjects had deficits in facial identity processing similar to those seen after right fusiform lesions, or complementary deficits affecting different aspects of face processing.We studied four alexic patients whose lesions involved the left fusiform gyrus and one prosopagnosic subject with a right fusiform lesion, on standard tests of face perception and recognition. We evaluated their ability first to process faces in linear contour images, and second to detect, discriminate, identify and integrate facial speech patterns into perception.We found that all five patients were impaired in face matching across viewpoint, but the alexic subjects performed worse with line-drawn faces, while the prosopagnosic subject did not. Alexic subjects could detect facial speech patterns but had trouble identifying them and did not integrate facial speech patterns with speech sounds, whereas identification and integration was intact in the prosopagnosic subject.We conclude that, in addition to their role in reading, the left-sided regions damaged in alexic subjects participate in the perception of facial identity but in a non-redundant fashion, focusing on the information in linear contours at higher spatial frequencies. In addition they have a dominant role in processing facial speech patterns, another visual aspect of language processing.

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Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family History of Breast Cancer and Folate Intake

Abstract

To evaluate the association between alcohol consumption and breast cancer risk in younger women, overall and by family history of breast cancer and folate intake, we prospectively followed 93,835 US women aged 27–44 years in Nurses' Health Study II who had alcohol consumption data in 1991. Alcohol consumption and folate intake were measured by food frequency questionnaire every 4 years. We documented 2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol consumption was not associated with breast cancer risk overall (for intake of ≥10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence interval: 0.94, 1.22). When the association was stratified by family history and folate intake, a positive association between alcohol consumption and breast cancer was found among women with a family history and folate intake less than 400 μg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06, 3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer in other categories of family history and folate intake (P-interaction = 0.55). In conclusion, in this population of younger women, higher alcohol consumption was associated with increased risk of breast cancer among those with both a family history of breast cancer and lower folate intake.

http://ift.tt/2iXZfdE

RE: “SMOKELESS TOBACCO USE AND THE RISK OF HEAD AND NECK CANCER: POOLED ANALYSIS OF US STUDIES IN THE INHANCE CONSORTIUM”

http://ift.tt/2iXZdT4

Maternal Dietary L-Arginine and Adverse Birth Outcomes in Dar es Salaam, Tanzania

Abstract

The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001–2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation.

http://ift.tt/2wzYZpM

THE AUTHORS REPLY

http://ift.tt/2iWUnWg

Particulate Matter and Risk of Hospital Admission in the Kathmandu Valley, Nepal: A Case-Crossover Study

Abstract

Air pollution is known to lead to a substantial health burden, but the majority of evidence is based on data from North America and Europe. Despite rising pollution levels, very limited information is available for South Asia. We investigated the impact of particulate matter with an aerodynamic diameter less than or equal to 10 μm (PM₁₀) on hospitalization, by cause and subpopulation, in the Kathmandu Valley, an understudied and rapidly urbanizing region in Nepal. Individual-level daily inpatient hospitalization data (2004–2007) were collected from each of 6 major hospitals, as Nepal has no central data collection system. Time-stratified case-crossover analysis was used with interaction terms for potential effect modifiers (e.g., age, sex, and socioeconomic status), with adjustment for day of the week and weather. Daily PM₁₀ concentrations averaged 120 μg/m³, with the daily maximum reaching 403 μg/m³. A 10-μg/m³ increase in PM₁₀ level was associated with increased risks of hospitalization of 1.00% (95% confidence interval (CI): 0.62, 1.38), 1.70% (95% CI: 0.18, 3.25), and 2.29% (95% CI: 0.18, 4.43) for total, respiratory, and cardiovascular admissions, respectively. We did not find strong evidence of effect modification by age, sex, or socioeconomic status. These results, in combination with the high levels of exposure, indicate a potentially serious human health burden from air pollution in the Kathmandu Valley.

http://ift.tt/2iXNvYv

Evaluating the Effectiveness of New York City Health Policy Initiatives in Reducing Cardiovascular Disease Mortality, 1990–2011

Abstract

Beginning in 2002, New York City (NYC) implemented numerous policies and programs targeting cardiovascular disease (CVD) risk factors. Using death certificates, we analyzed trends in NYC-specific and US mortality rates from 1990 to 2011 for all causes, any CVD, atherosclerotic CVD (ACVD), coronary artery disease (CAD), and stroke. Joinpoint analyses quantified annual percent change (APC) and evaluated whether decreases in CVD mortality accelerated after 2002 in either NYC or the total US population. Our analyses included 1,149,217 NYC decedents. The rates of decline in mortality from all causes, any CVD, and stroke in NYC did not change after 2002. Among men, the decline in ACVD mortality accelerated during 2002–2011 (APC = −4.8%, 95% confidence interval (CI): −6.1, −3.4) relative to 1990–2001 (APC = −2.3%, 95% CI: −3.1, −1.5). Among women, ACVD rates began declining more rapidly in 1993 (APC = −3.2%, 95% CI: −3.8, −2.7) and again in 2006 (APC = −6.6%, 95% CI: −8.9, −4.3) as compared with 1990–1992 (APC = 1.6%, 95% CI: −2.7, 6.0). In the US population, no acceleration of mortality decline was observed in either ACVD or CAD mortality rates after 2002. Relative to 1990–2001, atherosclerotic CVD and CAD rates began to decline more rapidly during the 2002–2011 period in both men and women—a pattern not observed in the total US population, suggesting that NYC initiatives might have had a measurable influence on delaying or reducing ACVD mortality.

http://ift.tt/2wzgsPc

Prediction of Multiple Recurrent Events: A Comparison of Extended Cox Models in Bladder Cancer

Abstract

Recurrence of bladder cancer can occur repeatedly in the same patient after treatment of the primary tumor. Models predicting the risk of a next recurrence may inform individualized decision-making on surveillance frequency. We aimed to assess the usefulness of extensions of the Cox proportional hazards model for repeated events in this context. We analyzed 531 Dutch patients with bladder cancer (1990–2012) with information on 7 prespecified predictors at the time of diagnosis of the primary and recurrent tumors. We considered 3 aspects of model variants: how to model time to the repeated events (calendar time, gap time, elapsed time); the number of preceding events (predictor, stratum variable); and the within-subject correlation (ignored in a simple Cox model, robust standard errors in a variance-correction model, random effect in a frailty model). First to fourth recurrences of bladder cancer occurred in 313, 174, 103, and 66 patients, respectively, with median calendar follow-up times of 1.1, 2.5, 3.8, and 4.5 years, respectively. We focused on gap time in the detailed analyses, allowing for clinically meaningful predictions. Variance-correction models may be useful if predictor selection is part of the model development. Frailty models may be useful when within-subject correlation is strong.

http://ift.tt/2iY5wpG

Rotating Night-Shift Work and the Risk of Breast Cancer in the Nurses' Health Studies

Abstract

In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using data from 2 prospective cohort studies, the Nurses' Health Study (1988–2012; n = 78,516) and Nurses' Health Study II (1989–2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk.

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Invited Commentary: Integrating Genomics and Social Epidemiology—Analysis of Late-Life Low Socioeconomic Status and the Conserved Transcriptional Response to Adversity

Abstract

Socially disadvantaged children face increased morbidity and mortality as they age. Understanding mechanisms through which social disadvantage becomes biologically embedded and devising measurements that can track this embedding are critical priorities for research to address social gradients in health. The analysis by Levine et al. (Am J Epidemiol. 2017;186(5):503–509) of genome-wide gene expression in a subsample of US Health and Retirement Study participants suggests important new directions for the field. Specifically, findings suggest promise in integrating gene expression data into population studies and provide further evidence for the conserved transcriptional response to adversity as a marker of biological embedding of social disadvantage. The study also highlights methodological issues related to the analysis of gene expression data and social gradients in health and a need to examine the conserved transcriptional response to adversity alongside other proposed measurements of biological embedding. Looking to the future, advances in genome science are opening new opportunities for sociogenomic epidemiology.

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Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles

Abstract

Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002–2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation.

http://ift.tt/2wzVdNd

Phenol Concentrations During Childhood and Subsequent Measures of Adiposity Among Young Girls

Abstract

Phenolic compounds represent a class of environmental chemicals with potentially endocrine-disrupting capabilities. We investigated longitudinal associations between childhood exposure to phenols, from both manmade and natural sources, and subsequent measures of adiposity among girls enrolled in the Breast Cancer and the Environment Research Program between 2004 and 2007. Baseline (ages 6–8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, the sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index (weight (kg)/height (m)²), waist circumference, and percent body fat were measured at annual or semiannual examinations through 2015 (n = 1,017). Linear mixed-effects regression was used to estimate how baseline concentrations of phenols (tertile groups) were related to changes in girls' adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A nonmonotonic association was observed for triclosan and girls' adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.

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Changes in the Inflammatory Potential of Diet Over Time and Risk of Colorectal Cancer in Postmenopausal Women

Abstract

We examined the associations between changes in dietary inflammatory potential and risk of colorectal cancer (CRC) in 87,042 postmenopausal women recruited from 1993–1998 by the Women's Health Initiative, conducted in the United States. Food frequency questionnaire data were used to compute patterns of change in dietary inflammatory index (DII) scores and cumulative average DII scores over 3 years. Cox regression models were used to estimate hazard ratios for CRC risk. After a median of 16.2 years of follow-up, 1,038 CRC cases were diagnosed. DII changes were not substantially associated with overall CRC, but proximal colon cancer risk was higher in the proinflammatory-change DII group than in the antiinflammatory-stable DII group (hazard ratio = 1.32, 95% confidence interval: 1.01, 1.74). Among nonusers of nonsteroidal antiinflammatory drugs (NSAIDs) (P_interaction = 0.055), the proinflammatory-stable DII group was at increased risk of overall CRC and proximal colon cancer. Also among nonusers of NSAIDs, risks of overall CRC, colon cancer, and proximal colon cancer were higher in the highest quintile compared with the lowest cumulative average DII quintile (65%, 61%, and 91% higher risk, respectively). Dietary changes toward, or a history of, proinflammatory diets are associated with an elevated risk of colon cancer, particularly for proximal colon cancer and among nonusers of NSAIDs.

http://ift.tt/2wzkvuQ

Traffic Congestion as a Risk Factor for Mortality in Near-Road Communities: A Case-Crossover Study

Abstract

Existing epidemiologic research on traffic largely neglects localized fluctuations. We leveraged finely resolved congestion data to investigate short-term associations with mortality in communities near roadways. We identified all nonaccidental, cardiovascular, cerebrovascular, and respiratory deaths (2009–2013) within 1 km of a highway in the Puget Sound region of Washington State. Using a case-crossover design, we examined the association of congestion 0–150 m, 151–300 m, and 301–1,000 m upwind of a decedent's home with mortality, adjusting for meteorology, holidays, and influenza activity. Among 9,449 deaths, we observed higher odds of cerebrovascular and respiratory mortality with greater upwind congestion, especially congestion near the decedent's home. For each 10-minute-km increase in upwind congestion within 150 m, the odds of cerebrovascular mortality were 1.08 (95% confidence interval (CI): 0.88, 1.33); within 151–300 m, the odds of cerebrovascular mortality were 1.05 (95% CI: 0.98, 1.12) times higher. We observed similar patterns for respiratory mortality, with 1.06 (95% CI: 0.76, 1.50) times higher odds of death with greater upwind congestion within 150 m and 1.02 (95% CI: 0.95, 1.10) times higher odds within 151–300 m. No increased odds of mortality were observed at greater distances, for overall mortality, or with downwind congestion. Unexpectedly, lower odds of cardiovascular mortality were suggested with greater congestion. This work demonstrates the use of nontraditional data to characterize the impacts of near-road exposures.

http://ift.tt/2iXz4np

Evaluating the Relationship Between Birth Weight for Gestational Age and Adult Blood Pressure Using Participants From a Cohort of Same-Sex Siblings, Discordant on Birth Weight Percentile

Abstract

Many studies have described an inverse relationship between birth weight and blood pressure (BP). Debate continues, however, over the magnitude and validity of the association. This analysis draws on the Early Determinants of Adult Health study (2005–2008), a cohort of 393 US adults (mean age 43 years; 47% male), including 114 same-sex sibling pairs deliberately sampled to be discordant on sex-specific birth weight for gestational age (BW/GA) in order to minimize confounding in studies of fetal growth and midlife health outcomes. Every quintile increment in BW/GA percentile was associated with a 1.04−mm Hg decrement in adult systolic BP (95% confidence interval (CI): −2.14, 0.06) and a 0.63−mm Hg decrement in diastolic BP (95% CI: −1.35, 0.09), controlling for sex, age, site, smoking, and race/ethnicity. The relationship was strongest among those in the lowest decile of BW/GA. Adding adult body mass index to the models attenuated the estimates (e.g., to −0.90 mm Hg (95% CI: −1.94, 0.14) for systolic BP). In the sibling-pair subgroup, associations were slightly stronger but with wider confidence intervals (e.g., −1.22 mm Hg (95% CI: −5.20, 2.75) for systolic BP). In conclusion, we found a small inverse relationship between BW/GA and BP in cohort and sibling-pair analyses, but the clinical or public health significance is likely limited.

http://ift.tt/2wzpags

Lifetime Alcohol Intake, Binge Drinking Behaviors, and Breast Cancer Risk

Abstract

The prevalence of binge drinking in the United States is rising. While alcohol is a risk factor for breast cancer, less is known about the impact of episodic heavy drinking. In 2003–2009, women aged 35–74 years who were free of breast cancer were enrolled in the Sister Study (n = 50,884). Residents of the United States or Puerto Rico who had a sister with breast cancer were eligible. Multivariable Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals for breast cancer. During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Increased breast cancer risk was observed for higher lifetime alcohol intake (for ≥230 drinks/year vs. <60 drinks/year, hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.15, 1.58). Relative to low-level drinkers (<60 drinks/year), hazard ratios were increased for ever binge drinking (HR = 1.29, 95% CI: 1.15, 1.45) or blacking out (HR = 1.39, 95% CI: 1.17, 1.64). Compared with low-level drinkers who never binged, moderate drinkers (60–229 drinks/year) who binged had a higher risk (HR = 1.25, 95% CI: 1.08, 1.44). There was evidence of effect modification between moderate lifetime drinking and binging (relative excess risk due to interaction = 0.33, 95% CI: 0.10, 0.57). Our findings support the established association between lifetime alcohol intake and breast cancer and provide evidence for an increased risk associated with heavy episodic drinking, especially among moderate lifetime drinkers.

http://ift.tt/2iWJSSH

Parental Body Mass Index and Behavioral Problems in Their Offspring: A Danish National Birth Cohort Study

Abstract

Maternal obesity has been associated with increased risk of offspring behavioral problems. We examined whether this association could be explained by familial factors by comparing associations for maternal body mass index (BMI) with associations for paternal BMI. We studied 38,314 children born to mothers enrolled in the Danish National Birth Cohort during 1996–2002. Data on maternal BMI was collected at 15 weeks of gestation, and paternal BMI was assessed when the child was 18 months old. When the child was 7 years old, the Strengths and Difficulties Questionnaire was completed by the parents. We estimated odds ratios for behavioral problems in offspring born to overweight/obese parents, and we found that maternal BMI was associated with offspring behavioral problems. Maternal BMI of 25.0–29.9 was associated with a 33% (odds ratio = 1.33, 95% confidence interval: 1.13, 1.57) higher risk of total difficulties in offspring, and maternal BMI of ≥30.0 was associated with an 83% (odds ratio = 1.83, 95% confidence interval: 1.49, 2.25) higher risk. Paternal obesity was also associated with higher risk of offspring behavioral problems, but stronger associations were observed with maternal prepregnancy obesity. Our results suggest that part of the association between maternal BMI and behavioral problems can be accounted for by genetic and social factors, but environmental risk factors may also contribute to the etiology of behavioral problems.

http://ift.tt/2wA8CoK

Study of polyamide thin film characteristics impact on permeability/selectivity performance and fouling behavior of forward osmosis membrane

Abstract

In recent years, forward osmosis (FO) has received considerable attention due to its huge potentials in water desalination. The thin film composite (TFC) membrane used in the FO desalination consists of a bottom support layer covered by an active layer on top. Polyamide (PA) is commonly employed as an active layer forming via interfacial polymerization between m-phenylenediamine (MPD) and trimesoyl chloride (TMC) monomers. In this study, the effects that the MPD and TMC concentrations could have on the performance and anti-fouling behavior of the obtained FO membrane have been investigated. Results showed that there is a trade-off relationship between the water flux and salt rejection, which by increasing MPD concentration, the water flux was reducedو while the salt rejection was enhanced. Also, by increasing the TMC concentration, an opposite trend was observed. Using 0.20 wt.% of TMC monomer, the highest water fluxes of 21.6 LMH and 29.3 LMH were achieved in two different membrane configurations. Furthermore, higher TMC concentration caused better anti-fouling property, when PA active layer of the membrane was in a high fouling potential environment.

http://ift.tt/2gACAQa

Modelling studies for photocatalytic degradation of organic dyes using TiO 2 nanofibers

Abstract

In this work, modelling of the photocatalytic degradation of para-nitrophenol (PNP) using synthesized electrospun TiO₂ nanofibers under UV light illumination is reported. A dynamic model was developed in order to understand the behaviour of operating parameters, i.e. light intensity and catalyst loading on the photocatalytic activity. This model was simulated and analysed for both TiO₂ solid nanofibers and TiO₂ hollow nanofibers, applied as photocatalysts in the Langmuir–Hinshelwood kinetic framework. The entire photocatalytic degradation rate follows pseudo-first-order kinetics. The simulated results obtained from the developed model are in good agreement with the experimental results. At a catalyst loading of 1.0 mg mL⁻¹, better respective degradation rates were achieved at UV light irradiance of 4 mW cm⁻², for both the TiO₂ solid and hollow nanofibers. However, it was also observed that TiO₂ hollow nanofibers have a higher adsorption rate than that of TiO₂ solid nanofibers resulting in a higher photocatalytic degradation rate of PNP.

http://ift.tt/2eFmeZv

Evaluation of the content of Zn, Cu, Ni and Pb as well as the enzymatic activity of forest soils exposed to the effect of road traffic pollution

Abstract

The paper evaluates the contents of total forms of selected heavy metals (Zn, Cu, Ni and Pb) as well as the activity of catalase (CAT), dehydrogenases (DEH), alkaline phosphatase (AlP) and acid phosphatase (AcP) in mineral surface horizons of forest soils exposed to the effect of road traffic pollutions. The sampling locations (n = 24) were determined in the area covered by the Szubin Forest along the exit road from Bydgoszcz to Poznań (provincial road no. 223). Soil was sampled 25 m away from the traffic lane, from two depths, 5–20 cm (humus horizons) and 20–50 cm (eluvial horizons). The contents of the heavy metals analysed were in the order of Pb > Zn > Cu > Ni. Despite intensive road traffic, with the Integrated Pollution Index (IPI) calculated, there was found a low pollution with nickel, average with zinc and copper and high with lead only. However, under the Regulation of the Minister of Environment, heavy metal values recorded allow for classifying the soils analysed as soils unpolluted with those metals. In the soil samples analysed, there were found significant positive dependencies between the content of clay fraction and zinc (r = 0.455; P < 0.05) and copper (r = 0.430; P < 0.05). With the enzyme activity results, values of the soil resistance index (RS) were calculated. The enzymes analysed were classified in the following decreasing order in terms of their resistance to traffic pollution: catalase > acid phosphatase > alkaline phosphatase > dehydrogenases (humus horizons) and catalase > dehydrogenases > alkaline phosphatase > acid phosphatase (eluvial horizons). Organic carbon showed a significant positive correlation with the activities of alkaline (r = 0.668; P < 0.05) and acid phosphatase (r = 0.668; P < 0.05) however not with catalase and dehydrogenases.

http://ift.tt/2gACzM6

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The post VideoEndocrinology™ Top-Viewed Videos appeared first on American Thyroid Association.

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Antimicrobial photodynamic therapy on treatment of infected radiation-induced oral mucositis: Report of two cases

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Alyne Simões, Bernar Monteiro Benites, Camila Benassi, Gabriella Torres-Schroter, Juliana Rodrigues de Castro, Luana Campos

http://ift.tt/2wBU5XS

Scholar : Ειδοποίηση Μελετητή - [ ΣΤΟΜΑ

Ειδοποίηση Μελετητή:[ ΣΤΟΜΑΤΙΤΙΣ ]

[HTML] Apremilast for treatment of recalcitrant aphthous stomatitis

F Schibler, K Heidemeyer, HW Klötgen… - JAAD Case Reports, 2017

Conclusion Apremilast is an orally administered small molecule that specifically inhibits
phosphodiesterase-4 and modulates the immune system by increasing the levels of
intracellular cyclic adenosine monophosphate and inhibiting interleukin (IL)-2, interferon-γ,

Stress as a Cause of Recurrent Aphthous Stomatitis and Its Correlation with Salivary Stress Markers.

UK Kunikullaya, MA Kumar, V Ananthakrishnan… - The Chinese journal of …, 2017

Stress causes an increase in cortisol and amylase. Recurrent aphthous stomatitis (RAS)
results due to a multitude of causes, amongst which stress is one of the most important. Aim
of the study was to estimate the level of stress, serum cortisol, salivary cortisol, amylase and

PFAPA-СИНДРОМ У ДІТЕЙ: ВИДАЛЯТИ ЧИ ЗБЕРІГАТИ МИГДАЛИКИ?

SA Levytska - Неонатологія, хірургія та перинатальна медицина, 2017

... PDF. Посилання. .1 Semianchuk VB. Periodic fever, aphthous stomatitis, pharyngitis and cervical
adenitis (pfapa) syndrome in children. Wiad Lek. ... 1. Semianchuk VB. Periodic fever, aphthous
stomatitis, pharyngitis and cervical adenitis (pfapa) syndrome in children. Wiad Lek. ...

[PDF] ONCOLYTIC VESICULAR STOMATITIS VIRUS INHIBITS CANCER CELL INVASION PROCESSES

DW GOAD - 2017

Oncolytic viruses (OVs) are being widely exploited as alternative treatment options for many
types of cancers due to their natural and/or engineered ability to preferentially target and
lyse cancer cells while sparing normal healthy cells.(Atherton and Lichty, 2013; Barlett et al.,

Neutralization of the potent neurotropic Chandipura virus via classical pathway is dependent on C1q

U Kunnakkadan, JB Johnson - Molecular Immunology, 2017

... After local infection, CHPV disseminates to the central nervous system causing marked damage
and even death. Studies on the closely related Vesicular Stomatitis Virus (VSV) have shown
that it activates the classical pathway resulting in virus neutralization. ...

[HTML] Proceedings of the 24 th Paediatric Rheumatology European Society Congress: Part three

E Atsali, D Kassara, P Katsimbri, S Boiu, DT Boumpas… - Pediatric Rheumatology, 2017

Skip to main content. Advertisement. Biomed Central ...

[HTML] Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R- …

M Uchida, Y Mori, T Nakamura, K Kato, K Kamezaki… - … and Pharmaceutical Bulletin, 2017

... Abdominal distension, hypertension, stomatitis, and headache were also observed, although
their frequencies were less than 10% in both the palonosetron and granisetron groups. ...
Hypertension, 2 (6.3%), 1 (2.4%), 0.077. Stomatitis, 2 (6.3%), 1 (2.4%), 0.077. ...

TNFRSF1A and MEFV mutations in childhood onset multiple sclerosis

A Blaschek, R v Kries, P Lohse, K Huss, K Vill… - European Journal of …, 2017

... 08 German, m, 13, RR, typical MRI* with high lesion load OCB's present, hemiparesis
hemihypoesthesia, Initially GLAT, currently Natalizumab, recurrent fever in childhood, aphthous
stomatitis, Diab.mellitus type I, father with MS and E148Q/P369S/R408Q MEFV mutation; Exon ...

Haematological parameters and serum biochemical assay of West African Dwarf goats infected with peste des petits ruminants virus in Nsukka, Enugu State

ICI Ugochukwu, EI Ugochukwu, CC Chukwu - Comparative Clinical Pathology, 2017

... It is a highly contagious viral disease of domestic and wild small ruminants characterised by
stomatitis, pyrexia, se- vere dehydration, emaciation, purulent ocular and nasal dis- charges,
pneumonia and severe diarrhoea and followed by hypothermia, and death usually occurs ...

[PDF] Oral Health Equals Total Health: A Brief Review

A Yap - Journal of Dentistry Indonesia, 2017

... addition, many drugs used to treat medical conditions can induce oral side effects, including
xerostomia (dry mouth), dysgeusia (distortion in perception of taste), and stomatitis (inflammatory
disease of the mouth).7 Some medical treatments may also result in oral infections and ...

Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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Scholar : Ειδοποίηση Μελετητή - [ ογκοι

Ειδοποίηση Μελετητή:[ ογκοι κεφαλης τραχηλου ]

[PDF] Μελέτη του βαθμού ενημέρωσης των ογκολόγων-παθολόγων ως προς το αντικείμενο της φαρμακογονιδιωματικής στην Ελλάδα

Π Τσιάκα - 2017

... Φυσικά οι γενετικές εξετάσεις μπορούν να γίνουν και σε τμήμα φρέσκου (μη-μονιμοποιημένου)
όγκου, εφόσον η ... έναν αιώνα βασιζόταν στην παθολογοανατομική εξέταση των όγκων. Τα τελευταία ...
όγκοι έχουν διαφορετικούς βιοδείκτες, οι τελευταίοι έχουν μεγάλη σημασία στην ...

Scholar : Ειδοποίηση Μελετητή - [ Decannulat

Ειδοποίηση Μελετητή:[ Decannulation ]

La chirurgia robotica transorale (TORS): Una nuova applicazione nelle decannulazioni ad alto rischio

F Montevecchi, G Cammaroto, G Meccariello, PT Hoff… - ACTA …, 2017

... Tracheostomy decannulation has always been considered a procedure with an
attendant risk, especially in patients with a reduced upper airway diameter as is
commonly observed in the obstructive sleep apnoea (OSA) population. ...

[HTML] Resection and anastomosis for benign tracheal stenosis: Single institution experience of 18 cases

A Kumar, BB Asaf, HV Puri, A Abdellateef - Lung India, 2017

... The indications for surgery were: symptomatic reduction in the tracheal diameter of more
than 50% (with stridor or dyspnea), failure of tracheostomy decannulation, or failure of
endoscopic management. All were elective, planned procedures. ...

ATS Core Curriculum 2017: Part III. Adult Critical Care Medicine

JI McSparron, MM Hayes, JT Poston, LA Seaburg… - Annals of the American …, 2017

Sequential use of extracorporeal devices to avoid mechanical ventilation in a patient with complicated pulmonary fibrosis

LO Harnisch, O Moerer - Journal of Artificial Organs, 2017

... Finally, the plan was to switch the devices to ECCO2R. The use of low-flow ECCO2R appeared
to be advantageous because of the option to control for CO2 extracorporeally and still being able
to mobilize the patient, with a lower risk of hazardous accidental decannulation. ...

Consensus Report by PALISI and PBMTC Joint Working Committees, Supportive Care Guidelines for Management of VOD in Children and Adolescents; Part 3: Focus …

N Ovchinsky, W Frazier, JJ Auletta, CC Dvorak… - Biology of Blood and …, 2017

... 79%. Further, Di Nardo et al reported 29 HCT patients from the ELSO registry in 2014,
of which 79% (n =23) died during ECMO support, 21% (n =6) survived to ECMO
decannulation and 10% (n =3) were discharged (22). Notably ...

Water and Air Caloric Tests in Patients with dizziness

SA via Forkhead - Otolaryngology–Head and Neck Surgery

... The questions were designed to gauge familiarity with emergency stay suture usage and to
assess job title, years of experience, and prior experience with accidental decannulation. ... Lack
of experience with accidental decannulation was PSQ i Page 3. P266 ...

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Δευτέρα 4 Σεπτεμβρίου 2017

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Abstract

[HTML] Apremilast for treatment of recalcitrant aphthous stomatitis

[PDF] ONCOLYTIC VESICULAR STOMATITIS VIRUS INHIBITS CANCER CELL INVASION PROCESSES

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[HTML] Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R- …

[PDF] Oral Health Equals Total Health: A Brief Review

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[HTML] Resection and anastomosis for benign tracheal stenosis: Single institution experience of 18 cases

[HTML] Spontaneous Breathing For the Difficult Airway

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