Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): Jana J. Anderson, Narisa D.M. Darwis, Daniel F. Mackay, Carlos A. Celis-Morales, Donald M. Lyall, Naveed Sattar, Jason M.R. Gill, Jill P. Pell
AimRed and processed meat may be risk factors for breast cancer due to their iron content, administration of oestrogens to cattle or mutagens created during cooking. We studied the associations in UK Biobank and then included the results in a meta-analysis of published cohort studies.MethodsUK Biobank, a general population cohort study, recruited participants aged 40–69 years. Incident breast cancer was ascertained via linkage to routine hospital admission, cancer registry and death certificate data. Univariate and multivariable Cox proportional hazard models were used to explore the associations between red and processed meat consumption and breast cancer. Previously published cohort studies were identified from a systematic review using PubMed and Ovid and a meta-analysis conducted using a random effects model.ResultsOver a median of 7 years follow-up, 4819 of the 262,195 women developed breast cancer. The risk was increased in the highest tertile (>9 g/day) of processed meat consumption (adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.08–1.35, p = 0.001). Collation with 10 previous cohort studies provided data on 40,257 incident breast cancers in 1.65 million women. On meta-analysis, processed meat consumption was associated with overall (relative risk [RR] 1.06, 95% CI 1.01–1.11) and post-menopausal (RR 1.09, 95% CI 1.03–1.15), but not pre-menopausal (RR 0.99, 95% CI 0.88–1.10), breast cancer. In UK Biobank and the meta-analysis, red meat consumption was not associated with breast cancer (adjusted HR 0.99 95% CI 0.88–1.12 and RR 1.03, 95% CI 0.99–1.08, respectively).ConclusionsConsumption of processed meat, but not red meat, may increase the risk of breast cancer.



http://ift.tt/2DpQxei

Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis: A population-based cohort study

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): G.M.H.E. Dackus, K. Jóźwiak, G.S. Sonke, E. van der Wall, P.J. van Diest, M. Hauptmann, S. Siesling, S.C. Linn
BackgroundPrior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients.In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR).Patients and methodsAll women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (45<years≤55; n = 304) and postmenopausal (>55 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation.ResultsDuring follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed.ConclusionAI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients.



http://ift.tt/2p91WvQ

3-Methoxytyramine: An independent prognostic biomarker that associates with high-risk disease and poor clinical outcome in neuroblastoma patients

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): I.R.N. Verly, A.B.P. van Kuilenburg, N.G.G.M. Abeling, S.M.I. Goorden, M. Fiocco, F.M. Vaz, M.M. van Noesel, C.M. Zwaan, G.J.L. Kaspers, J.H.M. Merks, H.N. Caron, G.A.M. Tytgat
IntroductionPrognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis.Patients and methodsRetrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis.ResultsMultivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001).ConclusionsElevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.



http://ift.tt/2DpQpLQ

Long-term follow-up of retinoblastoma survivors: Experience from India

Rachna Seth, Amitabh Singh, Vijay Guru, Bhavna Chawla, Sushmita Pathy, Savita Sapra

South Asian Journal of Cancer 2017 6(4):176-179

Background: Retinoblastoma (Rb) is the most common primary intraocular tumor of infancy and childhood. Survivors' ocular and visual problems and increased risk for subsequent malignancy are well documented, but data on long-term health status of Rb survivors are limited, this being particularly true for India. Methodology: Children who had completed treatment for Rb at least 2 years ago before and were under follow-up at the after cancer treatment clinic were evaluated. Results: In our series of 213 patients, the median age was 29 months, there was a male preponderance, and majority had unilateral disease. Enucleation was done in almost three-fourth and 3% underwent bilateral enucleation. Majority of the patients received chemotherapy, and few received radiation. Growth was affected in about one-third and majority were those who had received radiation. Diminished vision was noticed in about one-sixth. Orbital hypoplasia and contracted socket were seen in 14.1% cases. 2.7% were hearing impaired. About one-sixth had a global intelligence delay. Second neoplasms were seen in 0.01%. No other abnormalities were seen. Conclusions: Common late effects in our Rb survivors include diminished vision in the salvage eye, intellectual disability, and contracted socket; there is a need for timely institution of prosthesis to avoid late effects such as hypoplasia, contracted sockets, and better cosmesis and enhanced self-esteem. Second neoplasm is a concern. Lifelong follow-up and counseling of a healthy lifestyle are needed for Rb survivors.

http://ift.tt/2BxnbgV

Role of percutaneous computed tomography-guided radiofrequency ablation in treatment of osteoid osteoma

Ajay R Upadhyay, Nikunj Chandrakant Desai, Digish U Vaghela

South Asian Journal of Cancer 2017 6(4):139-140

Aim: The aim of the study was to evaluate efficacy of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) of nidus in osteoid osteoma (OO). Materials and Methods: RFA was performed on fifty patients with clinically and radiologically diagnosed OO. RFA was done in the department of radio-diagnosis in our institute (a tertiary care providing institute in Ahmedabad, Western India). Ablation was performed by putting at an electrode tip (3–5 mm) into nidus under CT guidance with targeted temperature of 90°C for 3 min. Results: All procedures were technically successful. No immediate major or minor complications were observed. Complete clinical success was achieved in 46 patients. Only four patients required second intervention. Conclusion: Our experience indicates a 98% success rate. No major complications were noted.

http://ift.tt/2zdnbwf

Male breast cancer: A retrospective review of clinical profile from a tertiary cancer care center of India

Dharma Ram, Suhas K Rajappa, Veda P Selvakumar, Himanshu Shukla, Ashish Goel, Rajeev Kumar, Kapil Kumar

South Asian Journal of Cancer 2017 6(4):141-143

Aim: Present study was done with an aim to analyse the clinicopathological and survival characteristics of male breast cancer patients. Methods: We did a retrospective review of our database and analysed total 27 patients who presented to breast oncology unit of Rajiv Gandhi cancer centre and research institute from January 2010 to April 2016. Results: Most common stage at presentation in our study was in stage II. The median follow up was 32.75 months. The actuarial 5-year survival was 92.30% and DFS was 76.30%. Only hormone receptor status was found as a significant prognostic variable among the prognostic factors studied for disease free survival. Conclusions: Carcinoma breast in male is a relatively rare disease and management principles are translated from our understanding of breast cancer in women. A relatively early stage at presentation is a contrasting finding of our series which may be responsible for a significantly better actuarial 5 year survival rates.

http://ift.tt/2BwPnR5

Myoepithelial carcinoma of the breast: Case report of a rare entity and its response to chemotherapy

Sanyo P Dsouza, Ajit Kulkarni, Nandini Sharma, SD Banavali

South Asian Journal of Cancer 2017 6(4):185-194



http://ift.tt/2zerTKg

Osimertinib in Indian patients with T790M-positive advanced nonsmall cell lung cancer

Vanita Noronha, Swaratika Majumdar, Amit Joshi, Vijay Patil, Vaishakhi Trivedi, Anuradha Chougule, Kumar Prabhash

South Asian Journal of Cancer 2017 6(4):143-146



http://ift.tt/2BwSwjI

Cutaneous Hodgkin's lymphoma

Asawari Anant Ambekar, Chitralekha S Soman

South Asian Journal of Cancer 2017 6(4):170-175



http://ift.tt/2zdXZ8X

Tolerance and adverse event profile with sorafenib in Indian patients with advanced hepatocellular carcinoma

Vikas Ostwal, Tarachand Gupta, Supriya Chopra, Sherly Lewis, Mahesh Goel, Shraddha Patkar, Nitin Shetty, Anant Ramaswamy

South Asian Journal of Cancer 2017 6(4):144-146

Background: The current standard of treatment for advanced hepatocellular cancer Hepatocellular carcinoma (HCC) is Sorafenib. Data regarding its tolerance and adverse event profile in Indian patients is scarce. Materials and Methods: The primary aim of this analysis was to assess the adverse events (Grade 3 and Grade 4 as per CTCAE v4.0) and requirements for dose reduction with sorafenib in advanced HCC. Details of consecutive patients started on 800 mg/day dosing were obtained from a prospectively maintained database (over a period of 6 months) and analyzed. Results: Thirty-nine patients were available for inclusion in the study. Median age was 58 years (range: 20–75). All patients were classified as Barcelona clinic liver cancer C. Common side effects seen were liver dysfunction (38.5%), hand-foot-syndrome-rash (HFSR) (Grade 2 and 3-25.6%), fatigue (Grade 2 and Grade 3–10.3%), and diarrhea (7.7%). Dose reduction was required in 43.6% of patients. Drug interruptions/cessation was required in 38.5% of patients within the first four months of treatment. Nearly 41% of patients required cessation of sorafenib due to intolerable side-effects while 28.2% stopped sorafenib due to progressive disease. At a median follow-up of 4.9 months, median event-free survival (EFS) was 4.20 months (95% confidence interval: 3.343–5.068). Conclusion: A higher incidence of liver dysfunction and HFSR is seen in Indian patients as compared to published data. A significant proportion of patients required cessation of sorafenib due to adverse events in our series. However, EFS remains on par with that seen in larger studies with sorafenib in advanced HCC.

http://ift.tt/2Bxi2Fx

Adolescents and young adults: A study of distribution of cancer at ages 15–39 years in a tertiary care hospital from North India: Epidemiological considerations

Neha Kakkar, Ajay Gupta, Neeraj Kumar Sharma, Prachi Agarwal, Jaspreet Kaur

South Asian Journal of Cancer 2017 6(4):180-182

Purpose: This study aimed to analyze cancer pattern among adolescents and young adults (AYA) in a tertiary care center in North India. Materials and Methods: A retrospective study from January 2011 to December 2014 was undertaken on AYA cancer patients (aged 15–39 years). Results: Totally 1077 cases of AYA cancers were identified for analyzing the frequency and pattern of cancer distribution. The most common cancer was head and neck (32%) followed by breast (14.2%). The distribution pattern was observed to be varying in different age groups with lymphoma, leukemia, bone tumors, and sarcomas in adolescents while carcinomas being more frequent in young adults. Conclusion: Cancer distribution patterns are distinct among AYA in terms of epidemiology and biology.

http://ift.tt/2zfqLGw

Metastatic anorectal melanomas – An exploratory retrospective analysis on the benefits of systemic therapy versus best supportive care in a resource-limited setting from India

Arvind Sahu, Anant Ramaswamy, Nitin Singhal, Vipul Doshi, Jimmy Mirani, Ashwin Desouza, Shripad Banavali, Avanish Saklani, Vikas Ostwal

South Asian Journal of Cancer 2017 6(4):147-150

Aim: Data regarding the optimal management of metastatic anorectal melanoma (mARM) is scarce. The primary aim was to evaluate the potential benefits of systemic therapy in mARM. Materials and Methods: This is a retrospective analysis of all mARM who presented between July 2013 and June 2015 at the Department of GI Medical Oncology, Tata Memorial Hospital. Results: Of a total of 37 patients, twelve patients were planned for best supportive care (BSC) only while the remaining 25 patients received systemic therapy. The median overall survival (OS) for the whole cohort was 27 weeks. The OS was significantly better in patients who received first-line therapy as compared to those who were offered BSC (median OS: 14 vs. 33 weeks; P = 0.04). Patients with PS of 1 did significantly better than PS of 2 more (OS 70 vs. 17 weeks; P = 0.015). Conclusion: mARM should be offered chemotherapy, especially in good performance patients. Paclitaxel/Platinum or Capecitabine/Temozolomide regimens can be considered as the preferred regime in the resource-limited setting where immunotherapy may not be a feasible option.

http://ift.tt/2BwPlIX

Profile of patients undergoing palliative radiotherapy: A single-institute study from a tertiary care oncology center

Virender Suhag, BS Sunita, Pankaj Vats, Nilotpal Chakravarty, Mayuri Jain, Rekha S Vashisht

South Asian Journal of Cancer 2017 6(4):190-193

Background: Palliative radiotherapy (PRT) plays a significant role in the palliation of symptoms in patients with cancer and constitutes nearly 50% of the workload in different settings. Aims: The aim is to study patient-, disease-, and treatment-related characteristics in locoregionally advanced and metastatic malignancies meriting palliative management. Setting and Design: This was a retrospective observational study in a tertiary care government institute with academic and research potential. Methodology: The electronic medical records, medical documents, and radiotherapy (RT) treatment charts were retrieved and studied. Observations: A total of 460 patients were included in the study over 2 years, forming 30% of the total number of patients treated during the study period. Three hundred and ninety-six patients received PRT to the metastatic sites, while 64 patients received extremely hypofractionated PRT to the primary for symptomatic relief. Totally 442 patients showed good symptomatic response to PRT. One hundred and thirty-eight patients underwent re-irradiation. Lung was the most common primary site seen in 155 cases. The most common indication for PRT was palliation of pain from painful metastases as seen in 240 cases, and the next common indication was palliative whole-brain RT for brain metastases as seen in 159 cases. Conclusion: PRT forms an integral and important aspect of palliative care to the vast number of patients harboring metastatic disease that warrants some form of treatment for symptomatic relief. Short course of PRT in outdoor setting is a preferred mode of treatment to improve the quality of life of these distressed patients.

http://ift.tt/2zerW8N

Musculoskeletal chronic graft versus host disease – A rare complication of allogeneic hematopoietic stem cell transplantation: A case report and review of its literature

Vasu Babu Goli, Reetu Jain, Ganapathi Bhat, Anjana Sainani, SH Advani

South Asian Journal of Cancer 2017 6(4):150-168



http://ift.tt/2BwPcoT

Regional reporting of the incidence of Anaplastic Lymphoma Kinase mutation in 379 non-small-cell lung cancer patients from Kolkata: Using immunohistochemistry as the diagnostic modality in a significant subset

Koushik Chatterjee, Raja Bhowmik, Bhargab Chattopadhyay

South Asian Journal of Cancer 2017 6(4):169-170

Context: Regional epidemiology of anaplastic lymphoma kinase (ALK) mutation in non-small-cell lung cancer (NSCLC) is an unmet need in India, and so is the knowledge of its incidence based on immunohistochemistry (IHC). Aims: Reporting the incidence of ALK mutation in NSCLC from Kolkata, incorporating IHC as the diagnostic modality in a considerable subset of patients. Subjects and Methods: It is a retrospective observational study done on NSCLC patients with adenocarcinoma histology, unselected by epidermal growth factor receptor, whose samples were tested for ALK mutation status between March 1, 2013, and March 15, 2017. The study involved all cancer facilities in Kolkata, except Tata Medical Centre. Up to June 2015, the tests were done by fluorescence in situ hybridization (FISH) and from July 2015 to the end, tests were done using IHC, as per the standard testing guidelines existing during the respective time periods. Results were documented in a de-identified manner to analyze the incidence of ALK mutations. Results: A total of 379 patients was tested for ALK mutations. March 2013 to June 2015, 200 (52.77%) patients were tested by FISH, 17 (8.5%) samples were unreportable and 4 patients [(2.19%) 4/183] tested positive for ALK mutations. From July 2015 to March 2017, 179 (47.22%) patients were tested by IHC, 9 (5.02%) samples were unreportable, and 10 patients [(5.88%) 10/170] tested positive for ALK mutations. Overall, 26 (6.8%) samples were unreportable and 14 [(3.9%) 14/353] patients tested positive for ALK mutations. Conclusions: The overall incidence of ALK mutation positive NSCLC in Kolkata is 3.9%. The incidence by IHC is 5.88% and by FISH is 2.19%, in the subset of patients tested by these two modalities respectively.

http://ift.tt/2zePqLb

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy

Suresh Babu Mallekavu, Aditi Harsh Thanky, Govind Babu Kanakasetty, Lakshmaiah Kuntegowdanahalli, Lokanatha Dasappa, Linu A Jacob

South Asian Journal of Cancer 2017 6(4):151-153

Context: Carcinoma cervix is a leading cause of cancer in Indian females where 15%–60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. Settings and Design: The study design was a retrospective analysis. Materials and Methods: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). Results: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. Statistical Analysis Used: It was carried out by SPSS software version 20. Conclusion: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research.

http://ift.tt/2BwP7S7

Clinicopathological and molecular epidemiological study of lung cancer patients seen at a tertiary care hospital in Northern India

Randeep Singh, Nitesh Rohtagi

South Asian Journal of Cancer 2017 6(4):171-175

Aims: The primary objective of this study was to estimate the clinicopathological and molecular profile of lung cancer patients along with the evaluation of their clinical characteristics at a tertiary care hospital in Northern India. Subjects and Methods: A total of 421 patients with lung cancer histology who were treated at Max Super Speciality Hospitals were included in the study. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and permission was obtained from the Ethics Committee before the start of the study. Clinical characteristics and molecular profiling data were collected from the patient's medical records. Results: There were 330 (78.4%) men and 91 (21.6%) women with a median age of 62 years (range: 30–93 years). Of the 421 patients, 388 (92.2%) patients had the nonsmall cell lung cancer (NSCLC) histology whereas 33 (7.8%) patients were of SCLC histology. Histology and gender had a significant association with NSCLC and SCLC (P < 0.05). Epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene testing was done in 120 and 93 patients, respectively. Of the 120 patients, 24 (20%) cases were positive for EGFR mutations whereas EML4-ALK fusion gene was present in 8 (8.6%) out of 93 patients. Conclusions: Our study confirms the importance of molecular testing in the NSCLC patient subgroup with an aim to identify the exact molecular targets that can benefit from the newer generation of targeted therapies.

http://ift.tt/2zeBDo1

Retraction: Recurrent Glioblastoma: Where we stand

South Asian Journal of Cancer 2017 6(4):153-153



http://ift.tt/2BwOY11

Good response to erlotinib in a patient after progression on osimertinib: A rare case of spatiotemporal T790M heterogeneity in a patient with epidermal growth factor receptor-mutant nonsmall cell lung cancer

Venkata Pradeep Babu Koyyala, Ullas Batra, Parveen Jain, Mansi Sharma, Pankaj Goyal, Kshitiz Domadia, Sneha Botra

South Asian Journal of Cancer 2017 6(4):179-185



http://ift.tt/2zeMKgD

Oncology gold standard® practical consensus recommendations for the use of monoclonal antibodies in the management of squamous cell carcinoma of head and neck

Govind Babu, Ankur Bahl, GS Bhattacharya, KT Bhowmik, PS Dattatraya, Nikhil Ghadyalpatil, SM Karandikar, Padmaj Kulkarni, Nithya Sridharan, Purvish Parikh, Kumar Prabhash, T Raja, S Rajasundaram, S Subramanian, Kaustav Talapatra, Ashok Vaid

South Asian Journal of Cancer 2017 6(4):154-160

We present the 2017 Oncology Gold Standard Practical Consensus Recommendation for use of monoclonal antibodies in the management of advanced squamous cell carcinoma of head neck region.

http://ift.tt/2Byf7fR

Epidemiology of cancer in young in central India: An analysis of rural cancer hospital data

Novak Gupta, Prakash Chitalkar, Renu Mishra, Ankur Punia

South Asian Journal of Cancer 2017 6(4):183-185

Background: Cancers in teenage and young adults (TYAs), though an increasing cause of mortality in our country, have been scarcely studied. The lack of studies of TYAs can significantly affect the outcomes of the youth in the prime of their lives. Aims: The aim of this study was to study the type of cancers in the TYA at a rural cancer center in central India. Design and Methods: A prospective study in the department of medical oncology, from the period of January 2013 till March 2016, was done. Data regarding socioepidemiological factors were collected for new cancer patients between the age group of 15–30 years in semi-structured questionnaire and from the hospital records. Cancers were classified according to the Birch classification. The cases were analyzed according to the epidemiological profile, classification of cancer, and age-wise distribution using descriptive analysis. Results: In this study, out of 5221 cancer patients, TYAs accounted for 327 (6.26%) with 189 males and 138 females (M: F– 1.37:1). The maximum cases were seen in 25–30 years' age group. Carcinoma was the most common malignancy (54.74%) with an increase from 19.56% in the 15–19 years' age group to 64.82% in the 25–30-year-old patients. Conclusion: The present study gives a glimpse of the TYA cancers in the central India. More than half of the young cancer patients suffer from carcinomas with about half of these being head and neck cancers.

http://ift.tt/2zdE4XV

Short message service prompted mouth self-examination in oral cancer patients as an alternative to frequent hospital-based surveillance

Sagar Vaishampayan, Akshat Malik, Prashant Pawar, Kavi Arya, Pankaj Chaturvedi

South Asian Journal of Cancer 2017 6(4):161-164

Introduction: Oral squamous cell carcinoma (OSCC) are amongst commonest cancer in the Indian sub-continent. After treatment, these patients require frequent followup to look for recurrences/second primary. Mouth Self Examination (MSE) has a great potential in all levels of prevention of oral cancer. However, the compliance to self-examination has been reported as poor. Mobile phone is a cheap and effective way to reach out to people. Short Message Service (SMS) is extremely popular can be a very effective motivational and interactive tool in health care setting. Methodology: We aimed to identify in adequately treated OSCC patients, the influence of health provider initiated SMS on the compliance to the MSE and to establish the efficacy of MSE by comparing patients' MSE interpretation via replies to the SMS with that of the experts' opinion on clinical examination status during follow up. Conclusion: We conclude that MSE can be very useful in adequately treated OSCC patients for evaluating disease status. All treated OSCC patients must be adequately educated for MSE as an integral part of treatment & follow-up protocol by the health provider facility. Health provider generated SMS reminders do improve motivation and compliance towards MSE but don't seem to reduce dropouts in follow up for large and diverse population like that in India.

http://ift.tt/2BzY8cT

EMERALD: Emergency visit audit of patients treated under medical oncology in a tertiary cancer center: Logical steps to decrease the burden

Amit Joshi, Vijay M Patil, Vanita Noronha, Anant Ramaswamy, Sudeep Gupta, Atanu Bhattacharjee, Avinash Bonda, MV Chandrakanth, Vikas Ostwal, Navin Khattry, Shripad Banavali, Kumar Prabhash

South Asian Journal of Cancer 2017 6(4):186-189

Background: We are a tertiary care cancer center and have approximately 1000–1500 emergency visits by cancer patients undergoing treatment under the adult medical oncology unit each month. However, due to the lack of a systematic audit, we are unable to plan steps toward the improvement in quality of emergency services, and hence the audit was planned. Methods: All emergency visits under the adult medical oncology department in the month of July 2015 were audited. The cause of visit, the demographic details, cancer details, and chemotherapy status were obtained from the electronic medical records. The emergency visits were classified as avoidable or unavoidable. Descriptive statistics were performed. Reasons for avoidable emergency visits were sought. Results: Out of 1199 visits, 1168 visits were classifiable. Six hundred and ninety-six visits were classified as unavoidable (59.6%, 95% CI: 56.7–62.4), 386 visits were classified as probably avoidable visit (33.0%, 95% CI: 30.4–35.8) whereas the remaining 86 (7.4%, 95% CI: 6.0–9.01) were classified as absolutely avoidable. Two hundred and ninety-seven visits happened on weekends (25.6%) and 138 visits converted into an inpatient admission (11.9%). The factors associated with avoidable visits were curative intention of treatment (odds ratio - 2.49), discontinued chemotherapy status (risk ratio [RR] - 8.28), and private category file status (RR – 1.89). Conclusion: A proportion of visits to emergency services can be curtailed. Approximately one-fourth of patients are seen on weekends, and only about one-tenth of patients get admitted.

http://ift.tt/2zdmuD9

How Well Does Dual-energy CT with Fast Kilovoltage Switching Quantify CT Number and Iodine and Calcium Concentrations?

Publication date: Available online 21 December 2017
Source:Academic Radiology
Author(s): Shingo Ohira, Tsukasa Karino, Yoshihiro Ueda, Yuya Nitta, Naoyuki Kanayama, Masayoshi Miyazaki, Masahiko Koizumi, Teruki Teshima
Rationale and ObjectivesBecause it is imperative for understanding the performance of dual-energy computed tomography scanner to determine clinical diagnosis, we aimed to assess the accuracy of quantitative measurements using dual-energy computed tomography with fast kilovoltage switching.Materials and MethodsQuantitative measurements were performed for 16 reference materials (physical density, 0.965–1.550 g/cm³; diameter of rod, 2.0–28.5 mm; iodine concentration, 2–15 mg/mL; and calcium concentration, 50–300 mg/mL) with varying scanning settings, and the measured values were compared to their theoretical values.ResultsFor high-density material, the maximum differences in Hounsfield unit values in the virtual monochromatic images at 50, 70, and 100 keV were −176.2, 61.0, and −35.2 HU, respectively, and the standard deviations over short- and long-term periods were 11.1, 6.1, and 3.5 HU at maximum. The accuracy of the Hounsfield unit measurement at 50 and 70 keV was significantly higher (P < 0.05) with higher radiation output and smaller phantom size. The difference in the iodine and calcium measurements in the large phantom were up to −2.6 and −60.4 mg/mL for iodine (5 mg/mL with 2-mm diameter) and calcium (300 mg/mL) materials, and the difference was improved with a small phantom. Metal artifact reduction software improved subjective image quality; however, the quantitative values were significantly underestimated (P < 0.05) (−49.5, −26.9, and −15.3 HU for 50, 70, and 100 keV, respectively; −1.0 and −17 mg/mL for iodine and calcium concentration, respectively) compared to that acquired without a metal material.ConclusionsThe accuracy of quantitative measurements can be affected by material density and the size of the object, radiation output, phantom size, and the presence of metal materials.



http://ift.tt/2kD1UaR

Breast Imaging Outcomes following Abnormal Thermography

Publication date: Available online 21 December 2017
Source:Academic Radiology
Author(s): Colleen H. Neal, Kelsey A. Flynt, Deborah O. Jeffries, Mark A. Helvie
Rationale and ObjectivesThe study aimed to determine the outcome of patients presenting for evaluation of abnormal breast thermography.Materials and MethodsFollowing Institutional Review Board approval, retrospective search identified 38 patients who presented for conventional breast imaging following a thermography-detected abnormality. Study criteria included women who had mammogram and/or breast ultrasound performed for evaluation of a thermography-detected abnormality between January 1, 2000, and December 31, 2015. Patients whose mammograms and ultrasounds were initiated at an outside institution or who did not have imaging at our institution were excluded. Records were reviewed for clinical history, thermography results, mammogram and/or ultrasound findings, and pathology. Mammograms and ultrasounds were prospectively interpreted by one of 14 Mammography Quality Standards Act–certified breast imaging radiologists with 3–30 years of experience. Patient outcomes were determined by biopsy or at least 1 year of follow-up. Patient ages ranged from 23 to 70 years (mean = 50 years).ResultsNinety-five percent (36 of 38) of patients did not have breast cancer. The two patients diagnosed with breast cancer had suspicious clinical symptoms including palpable mass and erythema. No asymptomatic woman had breast cancer. Negative predictive value was 100%. Of 38 patients, 79% (30 of 38) had Breast Imaging Reporting and Data System (BI-RADS) 1 or 2 assessments; 5% (2 of 38) had BI-RADS 3; and 16% (6 of 38) had BI-RADS 4 (n = 5) or BI-RADS 5 (n = 1) assessments. Two of six patients with biopsy recommendations were diagnosed with breast cancer (Positive predictive value 2 = 33.3%). All findings recommended for biopsy were ipsilateral to the reported thermography abnormality.ConclusionsNo cancer was diagnosed among asymptomatic women. The 5% of patients diagnosed with cancer had co-existing suspicious clinical findings. Mammogram and/or ultrasound were useful in accurately characterizing patients with abnormal thermography.



http://ift.tt/2kWZQKc

Autophagy and proteostasis in the control of synapse aging and disease

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): YongTian Liang, Stephan Sigrist
The maintenance of neuronal homeostasis is severely threatened by aging, probably partially due to compromised autophagic clearance. Hence, rejuvenating autophagy in aging neurons is considered a promising strategy to restore cognitive performance. Research in recent years has shown that autophagosome biogenesis takes place mainly in distal axons and, thus, close to presynaptic specializations, and that efficient macro-autophagy is essential for neuronal homeostasis and survival. Retrograde transport of autophagosomes might play a role in neuronal signaling processes, promoting neuronal complexity and preventing neurodegeneration. Here, we discuss recent advances concerning the intersection of aging, neurodegeneration and autophagy, and try to create a unified view of how neuronal autophagy and proteostasis might control synaptic aging and disease.



http://ift.tt/2Dsibra

Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction

Publication date: Available online 21 December 2017
Source:Cell Stem Cell
Author(s): Kazutaka Miyamoto, Mizuha Akiyama, Fumiya Tamura, Mari Isomi, Hiroyuki Yamakawa, Taketaro Sadahiro, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Hidenori Tani, Li Wang, Li Qian, Makoto Inoue, Yoshinori Ide, Junko Kurokawa, Tsunehisa Yamamoto, Tomohisa Seki, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expression and are inefficient. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT in reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial infarction. Thus, efficient, non-integrating SeV vectors may serve as a powerful system for cardiac regeneration.

Graphical abstract

Teaser

Ieda and colleagues show that non-integrating Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently reprogrammed mouse and human fibroblasts into induced cardiomyocyte-like cells. In vivo delivery of SeV vectors enhanced in vivo cardiac reprogramming compared to conventional retrovirus vectors, improved cardiac function, and reduced fibrosis after myocardial infarction.


http://ift.tt/2BLrbHp

Radial Glial Fibers Promote Neuronal Migration and Functional Recovery after Neonatal Brain Injury

Publication date: Available online 21 December 2017
Source:Cell Stem Cell
Author(s): Hideo Jinnou, Masato Sawada, Koya Kawase, Naoko Kaneko, Vicente Herranz-Pérez, Takuya Miyamoto, Takumi Kawaue, Takaki Miyata, Yasuhiko Tabata, Toshihiro Akaike, José Manuel García-Verdugo, Itsuki Ajioka, Shinji Saitoh, Kazunobu Sawamoto
Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation. Transplanting an N-cadherin-containing scaffold into injured neonatal brains likewise promotes migration and maturation of V-SVZ-derived neuroblasts, leading to functional improvements in impaired gait behaviors. Together these results suggest that RG fibers enable postnatal V-SVZ-derived neuroblasts to migrate toward sites of injury, thereby enhancing neuronal regeneration and functional recovery from neonatal brain injuries.

Graphical abstract

Teaser

Radial glia cells generate neuroblasts during embryonic cortical development and disappear soon after birth. Sawamoto and colleagues show that radial glia fibers are maintained in neonatal cortex in response to brain injury and support migration of postnatal V-SVZ-derived neurons, leading to behavioral recovery


http://ift.tt/2BLri5N

Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML

Publication date: Available online 21 December 2017
Source:Cell Stem Cell
Author(s): Delfim Duarte, Edwin D. Hawkins, Olufolake Akinduro, Heather Ang, Katia De Filippo, Isabella Y. Kong, Myriam Haltalli, Nicola Ruivo, Lenny Straszkowski, Stephin J. Vervoort, Catriona McLean, Tom S. Weber, Reema Khorshed, Chiara Pirillo, Andrew Wei, Saravana K. Ramasamy, Anjali P. Kusumbe, Ken Duffy, Ralf H. Adams, Louise E. Purton, Leo M. Carlin, Cristina Lo Celso
Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.

Graphical abstract

Teaser

Multi-modal microscopy of acute myeloid leukemia progression within the bone marrow reveals focal and progressive remodeling of endosteal blood vessels coupled to loss of osteoblasts, hematopoietic stem cells (HSCs), and HSC niches. Preserving endosteal vessels increases the number of surviving HSCs and improves the efficacy of chemotherapy.


http://ift.tt/2BM9fwb

A novel hydrophilic pyridinium salt polymer/SWCNTs composite film for high thermoelectric performance

Publication date: Available online 21 December 2017
Source:Polymer
Author(s): Sanyin Qu, Qin Yao, Liming Wang, Jianli Hua, Lidong Chen
Polymer/carbon nanotube composites have gained great progress in the past decade. However, the lack of scalability of production due to the relatively high volatility and strong toxicity of the dispersion solvent have created a great need for environmental friendly process for expanding TE applications. In this work, organic-inorganic composite films composed of a novel hydrophilic pyridinium salt polymer (noted as P2) and SWCNTs were prepared for thermoelectric application. The novel hydrophilic pyridinium salt polymer was designed and synthesized containing the pyridinium salt for aqueous dissolution and thiophenes as the conjugation group to make the polymer/CNT composite film electrical connecting, therefore improving the thermoelectric performance. Another pyridinium salt polymer (noted as P1) without thiophene group was also synthesized for the purpose of comparison. The polymers attach on the surface of CNTs through π-π conjugation interaction between conjugation groups and π-electrons of CNTs. The P2/CNT composites were homogeneously dispersed in the aqueous solution, revealing better dispersion behavior than P1/CNT, which is probably because of the stronger contact interaction between P2/CNT than P1/CNT due to the higher electron delocalization of polymer P2 than P1. The electrical conductivity of P2/CNT composite film reached the maximum value of 159 S/cm with 50% CNT content. Consequently, a high power factor of 46.4 μW/mK² was obtained for the P2/50%CNT composite film.

Graphical abstract

http://ift.tt/2CUXxPt

Automatic, simultaneous control of polymer composition and molecular weight during free radical copolymer synthesis

Publication date: Available online 21 December 2017
Source:Polymer
Author(s): Terry McAfee, Rick D. Montgomery, Thomas Zekoski, Aide Wu, Wayne F. Reed
Fully automatic, simultaneous control of polymer composition and molecular weight trajectories during free radical copolymer synthesis was achieved by coupling the continuous ACOMP data stream into a feedback controller which operated pumps for reactor feed of comonomers. The controller operates without recourse to a detailed kinetic model or reactivity ratios. Rather, it uses the fact that instantaneous copolymer chain composition is related to the instantaneous rate of consumption of comonomers, and the rate for each of these is described by rates α1 and α2 for comonomers 1 and 2, respectively. The instantaneous weight average molecular weight Mw,inst is proportional to total comonomer concentration via a constant p. Hence, target trajectories for composition and Mw can be independently prescribed and followed. Since α1, α2 and p are directly measurable from the ACOMP data stream, their values can be constantly updated by the automatic controller during the reaction process to insure the target trajectories are followed.

Graphical abstract

http://ift.tt/2BMtpWV

Duplex Sonography of Vertebral Arteries for Evaluation of Patients with Acute Vertigo

Publication date: Available online 21 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Peiman Nazerian, Sofia Bigiarini, Rudi Pecci, Lucia Taurino, Marco Moretti, Andrea Pavellini, Elisa Capretti, Stefano Grifoni, Simone Vanni
We evaluated the role of vertebral artery extracranial color-coded duplex sonography (VAECCS) in predicting vertebrobasilar stroke in consecutive patients presenting to the emergency department with vertigo of suspected ischemic origin. The final diagnosis was established by a panel of experts consisting of an emergency physician, a neurologist, and an otoneurologist. Vertebrobasilar stroke was diagnosed when an acute brain ischemic lesion congruent with symptoms was detected by neuroimaging during the index visit or a stroke was diagnosed within a 3-mo period after emergency department presentation. Among 126 patients, 28 (22%) were diagnosed with vertebrobasilar stroke. Fifteen (75%) of 20 patients with abnormal VAECCS results and 13 (12%) of 106 with normal VAECCS results had a final diagnosis of vertebrobasilar stroke. The sensitivity and specificity of VAECCS were 53.6% and 94.9%, respectively. Detecting an abnormal flow pattern at VAECCS significantly increased the risk of vertebrobasilar stroke (odds ratio = 21.5). The flow patterns most frequently related to vertebrobasilar stroke were absence of flow and high resistance pattern velocity (odds ratio = 9.3 and 22.7, respectively). VAECCS predicts vertebrobasilar stroke and could be a useful bedside screening tool in patients with vertigo.



http://ift.tt/2kWypQT

Ketamine Inhibits Ultrasound Stimulation-Induced Neuromodulation by Blocking Cortical Neuron Activity

Publication date: Available online 21 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Sungmin Han, Minkyung Kim, Hyungmin Kim, Hyunjoon Shin, Inchan Youn
Ultrasound (US) can be used to noninvasively stimulate brain activity. However, reproducible motor responses evoked by US are only elicited when the animal is in a light state of anesthesia. The present study investigated the effects of ketamine on US-induced motor responses and cortical neuronal activity. US was applied to the motor cortex of mice, and motor responses were evaluated based on robustness scores. Cortical neuronal activity was observed by fluorescence calcium imaging. US-induced motor responses were inhibited more than 20 min after ketamine injection, and US-triggered Ca²⁺ transients in cortical neurons were effectively blocked by ketamine. Our results indicate that ketamine suppresses US-triggered Ca²⁺ transients in cortical neurons and, therefore, inhibits US-induced motor responses in a deep anesthetic state.



http://ift.tt/2kDbjzh

Ultrasound Monitoring of Jugular Venous Pulse during Space Missions: Proof of Concept

Publication date: Available online 21 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Paolo Zamboni, Francesco Sisini, Erica Menegatti, Angelo Taibi, Giacomo Gadda, Valentina Tavoni, Anna Maria Malagoni, Mirko Tessari, Sergio Gianesini, Mauro Gambaccini
The jugular venous pulse (JVP) is one of the main parameters of cardiac function and is used by cardiologists in diagnosing heart failure. Its waveform comprises three positive waves (a, c and v) and two negative waves (x and y). Recently, it was found that JVP can be extrapolated from an ultrasound (US) video recording of the internal jugular vein (IJV), suggesting its application in space missions, on which US scanners are already widely used. To date, the feasibility of assessing JVP in microgravity (microG) has not been investigated. To verify the feasibility of JVP assessment in microG, we tested a protocol of self-performed B-mode ultrasound on the International Space Station (ISS). The protocol consisted of a video recording of IJV synchronized with electrocardiogram that produces a cross-sectional area time trace (JVP trace) (in cm²). The scans were acquired in six experimental sessions; two pre-flight (BDC1 and -2), two in space (ISS1 and -2) and two post-flight (Houston PF1, Cologne PF2). We measured the mean and standard deviation of the JVP waves and the phase relationship between such waves and P and T waves on the electrocardiogram. We verified that such parameters had the same accuracy on Earth as they did under microG, and we compared their values. The sensitivity, specificity and accuracy of JVP trace in microgravity are higher than those on Earth. The sequence of (a, c, and v) ascents and (x and y) descents along the cardiac cycle in microG is the same as that on Earth. The cause-and-effect relationship between the P and T waves on the electrocardiogram and a and v waves, respectively, of JVP is also confirmed in microG. Our experiment indicated the feasibility of deriving a JVP trace from a B-mode US examination self-performed by an astronaut in microG.



http://ift.tt/2kVqJhE

Multiple time courses of somatosensory responses in human cortex

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): P. Avanzini, V. Pelliccia, G. Lo Russo, G.A. Orban, G. Rizzolatti
Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli.



http://ift.tt/2kCIOBM

A probabilistic atlas of human brainstem pathways based on connectome imaging data

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Yuchun Tang, Wei Sun, Arthur W. Toga, John M. Ringman, Yonggang Shi
The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles for each subject, which were then used to calculate the probabilistic atlases in the MNI152 space for public release. In our experimental results, we demonstrate that our method yielded anatomically faithful reconstruction of the brainstem pathways and achieved improved performance in comparison with an existing atlas of cerebellar peduncles based on HCP data. These atlases have been publicly released on NITRIC (http://ift.tt/2kCIOlg) and can be readily used by brain imaging researchers interested in studying brainstem pathways.



http://ift.tt/2kVHgCq

Editorial Board

Publication date: February 2018
Source:Brain and Development, Volume 40, Issue 2





http://ift.tt/2DpY393

Announcements and reports

Publication date: February 2018
Source:Brain and Development, Volume 40, Issue 2





http://ift.tt/2kVw88t

Cover

Publication date: February 2018
Source:Brain and Development, Volume 40, Issue 2





http://ift.tt/2DpifaY

Contents

Publication date: February 2018
Source:Brain and Development, Volume 40, Issue 2





http://ift.tt/2kVSeaX

VE-Cadherin regulates the self-renewal of mouse embryonic stem cells via LIF/Stat3 signaling pathway

Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Ningning He, Xiaoniao Chen, Dan Wang, Ke Xu, Lingling Wu, Yuanyuan Liu, Hongyan Tao, Qinjun Zhao, Xiaocang Cao, Yuhao Li, Na Liu, Xin Qi, Zhongchao Han, Deling Kong, Jun Yang, Zongjin Li
With the abilities of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for stem cell-based therapeutics. However, the maintenance of ES cells with mouse embryonic fibroblasts (MEFs) can limit the clinical translation of ES cells. In the present study, we synthesized a fusion protein of the immunoglobulin G (IgG) fragment crystallizable region and vascular endothelial cadherin (VE-cadherin) extracellular domain (VE-cad-Fc) as a substrate for mouse ES cell culture, and we hypothesized that VE-cadherin could enhance the pluripotency and self-renewal of ES cells. Furthermore, we introduced a Stat3 reporter imaging system into ES cells and investigated the mechanism of the pluripotency enhancement mediated by VE-cadherin through cultured ES cells on VE-cad-Fc-coated plates using molecular imaging techniques. The resulting data revealed that VE-cad-Fc could activate the Stat3 signaling pathway, leading to the upregulation of stemness-related markers SSEA-1 and alkaline phosphatase (ALP). Moreover, VE-cad-Fc recovered the expression of Oct4, c-Myc, Nanog, Sox2, Tbx3 and Klf4 in differentiated ES cells, as well as enhanced the pluripotency of ES cells. In conclusion, VE-cadherin fusion protein coating methods provide an alternative towards feeder free culture of ES cells, and the strategy developed in the present study may benefit the clinical translation of ES cell-based therapeutics.



http://ift.tt/2BOzqTc

Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment

Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Xiao Zhao, Xiuchao Wang, Wei Sun, Keman Cheng, Hao Qin, Xuexiang Han, Yu Lin, Yongwei Wang, Jiayan Lang, Ruifang Zhao, Xiaowei Zheng, Ying Zhao, Jian shi, Jihui Hao, Qing Robert Miao, Guangjun Nie, He Ren
Low chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Using immunohistochemical evaluation, we investigated that decreased expression of human equilibrative nucleoside transporter-1 (hENT1, which is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity. To solve these problems, we employed a nanomedicine-based formulation of cationic liposomes for co-delivery of GEM along with siRNA targeting RRM2. Due to the specific endocytic uptake mechanism of nanocarriers and gene-silencing effect of RRM2 siRNA, this nanomedicine formulation significantly increased GEM chemosensitivity in tumor models of genetically engineered Panc1 cells with low hENT1 or high RRM2 expression. Moreover, in a series of patient-derived cancer cells, we demonstrated that the therapeutic benefits of the nanomedicine formulations were associated with the expression levels of hENT1 and RRM2. In summary, we found that the essential factors of GEM chemosensitivity were the expression levels of hENT1 and RRM2, and synthesized nanoformulations can overcome these problems. This unique design of nanomedicine not only provides a universal platform to enhance chemosensitivity but also contributes to the precision design and personalized treatment in nanomedicine.

Graphical abstract

http://ift.tt/2CSuKeb

Cost-effectiveness of adjuvant intravaginal brachytherapy in high-intermediate risk endometrial carcinoma

Publication date: Available online 21 December 2017
Source:Brachytherapy
Author(s): John M. Stahl, Shari Damast, Trevor J. Bledsoe, Yi An, Vivek Verma, James B. Yu, Melissa R. Young, Nataniel H. Lester-Coll
PURPOSEWe assessed the cost-effectiveness of adjuvant intravaginal brachytherapy (IVBT) vs. observation after total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) for high-intermediate risk (HIR) endometrial carcinoma.Methods AND MATERIALSA Markov model was used to assess the cost-effectiveness of IVBT by comparing average cumulative costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) between patients allocated to (1) 'observation' or (2) 'IVBT' after TH/BSO. We used a prototype Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)–defined HIR patient in the base case analysis. We calibrated the model to match the outcomes reported in the PORTEC-1 and PORTEC-2 trials. Utilities were obtained from published estimates, and costs were calculated based on Medicare reimbursement ($5445 for IVBT). The societal willingness-to-pay threshold was set at $100,000 per QALY. The time horizon was 5 years.ResultsIVBT was associated with a net increase of 0.094 QALYs (4.512 vs. 4.418) as well as an increase in mean cost ($17,453 vs. $15,620) relative to observation. The ICER for IVBT was $19,500 per QALY. On one-way sensitivity analysis, IVBT remained cost-effective when its cost was less than $12,937. If the probability of vaginal recurrence in the observation arm was increased or decreased by 25%, the ICER became $1335 per QALY and $87,925 per QALY, respectively. Probabilistic sensitivity analysis revealed that IVBT was the preferred management option in 86% of simulations.ConclusionsIVBT is cost-effective compared with observation after TH/BSO for HIR endometrial carcinoma by commonly accepted willingness-to-pay thresholds.



http://ift.tt/2kBeI1r

Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non–small cell lung cancer—A meta-analysis

Publication date: Available online 21 December 2017
Source:Brachytherapy
Author(s): Wenchao Zhang, Jiawei Li, Ran Li, Ying Zhang, Mingyong Han, Wei Ma
PURPOSEThis meta-analysis was conducted to investigate the efficacy and safety of ¹²⁵I brachytherapy for locally advanced non–small cell lung cancer (NSCLC).Methods AND MATERIALSTrials comparing ¹²⁵I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS).ResultsFifteen studies including 1188 cases were included. The pooled result indicated that there were significant differences in ORR, DCR, and OS between ¹²⁵I brachytherapy combined with chemotherapy and chemotherapy alone, but no statistic differences in gastrointestinal symptoms, leukopenia, myelosuppression, and hemoglobin reduction. Patients treated with ¹²⁵I brachytherapy combined with chemotherapy have a higher relative risk of pneumothorax, bloody sputum, and pneumorrhagia compared with chemotherapy alone. Seeds migration only occurred in the group treated with ¹²⁵I brachytherapy. There were significant differences in ORR, DCR, and myelosuppression between ¹²⁵I brachytherapy alone and chemotherapy.Conclusions¹²⁵I brachytherapy combined with chemotherapy can significantly enhance the clinical efficacy and improve the OS of patients with advanced NSCLC without increasing the incidence of complications of chemotherapy. ¹²⁵I brachytherapy alone can significantly enhance the clinical efficacy and reduce the incidence of myelosuppression compared with chemotherapy. However, ¹²⁵I brachytherapy may cause lung injury. Large sample and higher-quality randomized controlled trials are needed to confirm the pooled results of complications.



http://ift.tt/2kVoQle

Fabrication of ZnS with necklace-like hierarchical structure-decorated graphene and its photocatalytic performance

Publication date: April 2018
Source:Journal of Physics and Chemistry of Solids, Volume 115
Author(s): Bin Zeng, Wujun Zeng, Wanfeng Liu, Can Jin
In this study, we used a microwave reaction to fabricate necklace-like ZnS with a hierarchical structure dispersed on the surface of graphene sheets (ZnS NHS-G). The structure and properties of the ZnS NHS-G were characterized based on X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, photoluminescence spectroscopy, electrochemical impedance spectroscopy, and the photocurrent response. The results showed that a clear increase in the photocatalytic performance was achieved with ZnS NHS-G, which was attributed to the longer lifetime of the photogenerated electrons. Furthermore, the unique morphology of the necklace-like hierarchical structure enhanced its photocatalytic properties. Thus, this semiconductor may be used as an efficient photocatalyst in the future.



http://ift.tt/2p8z8Ub

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health

Publication date: Available online 21 December 2017
Source:Cell Host & Microbe
Author(s): Jun Zou, Benoit Chassaing, Vishal Singh, Michael Pellizzon, Matthew Ricci, Michael D. Fythe, Matam Vijay Kumar, Andrew T. Gewirtz
Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function.

Graphical abstract

Teaser

Dietary fiber supplements suppress adiposity and the associated parameters of metabolic syndrome. Zou et al. show that the fermentable fiber inulin impacts gut microbiota to increase intestinal epithelial proliferation, prevent colonic atrophy, reduce microbiota encroachment into the mucosa, and thereby protect against metabolic syndrome in a microbiota- and IL-22-dependent manner.


http://ift.tt/2BNI6Jw

Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth

Publication date: Available online 21 December 2017
Source:Cell Host & Microbe
Author(s): Caroline C. Gillis, Elizabeth R. Hughes, Luisella Spiga, Maria G. Winter, Wenhan Zhu, Tatiane Furtado de Carvalho, Rachael B. Chanin, Cassie L. Behrendt, Lora V. Hooper, Renato L. Santos, Sebastian E. Winter
During Salmonella-induced gastroenteritis, mucosal inflammation creates a niche that favors the expansion of the pathogen population over the microbiota. Here, we show that Salmonella Typhimurium infection was accompanied by dysbiosis, decreased butyrate levels, and substantially elevated lactate levels in the gut lumen. Administration of a lactate dehydrogenase inhibitor blunted lactate production in germ-free mice, suggesting that lactate was predominantly of host origin. Depletion of butyrate-producing Clostridia, either through oral antibiotic treatment or as part of the pathogen-induced dysbiosis, triggered a switch in host cells from oxidative metabolism to lactate fermentation, increasing both lactate levels and Salmonella lactate utilization. Administration of tributyrin or a PPARγ agonist diminished host lactate production and abrogated the fitness advantage conferred on Salmonella by lactate utilization. We conclude that alterations of the gut microbiota, specifically a depletion of Clostridia, reprogram host metabolism to perform lactate fermentation, thus supporting Salmonella infection.

Graphical abstract

Teaser

Intestinal infection with Salmonella Typhimurium results in inflammation-induced dysbiosis. Gillis et al. demonstrate that depletion of commensal Clostridia reduces butyrate availability and subsequently alters host metabolism to produce lactate. Lactate oxidation by Salmonella enhances fitness in the gut and allows the pathogen to outcompete the microbiota.


http://ift.tt/2BOEJC9

Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration

Publication date: Available online 21 December 2017
Source:Cell Host & Microbe
Author(s): Bjoern O. Schroeder, George M.H. Birchenough, Marcus Ståhlman, Liisa Arike, Malin E.V. Johansson, Gunnar C. Hansson, Fredrik Bäckhed
Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.

Graphical abstract

Teaser

The inner colonic mucus layer separates gut bacteria from their host. Schroeder et al. now find that gut bacteria can mediate functional defects of the mucus layer of mice fed a Western style diet. The defects can be prevented by application of a probiotic bifidobacteria or the prebiotic fiber inulin.


http://ift.tt/2BL30Zt

Discovery of EBI-1051: a novel and orally efficacious MEK inhibitor with benzofuran scaffold

Publication date: Available online 20 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Biao Lu, Song Huang, Jingsong Cao, Qiyue Hu, Ru Shen, Hong Wan, Dan Wang, Jijun Yuan, Lei Zhang, Jiayin Zhang, Minsheng Zhang, Weikang Tao, Lianshan Zhang
A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers. Compared to AZD6244, EBI-1051 showed superior potency in some cancer cell lines such as colon-205, A549 and MDA-MB-231

Graphical abstract

http://ift.tt/2zbPaMO

Synthesis and biological evaluation of cyclopeptide GG-8-6 and its analogues as anti-hepatocellular carcinoma agents

Publication date: Available online 20 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jie-Tao Chen, Ru Ma, Shi-Chang Sun, Xiao-Feng Zhu, Xiao-Li Xu, Qing Mu
GG-8-6, cyclo-(Val-Leu-Pro-Ile-Leu-Leu-Leu-Val-Leu, compound 1), and its twelve analogues (compound 2 - 13) were synthesized based on the lead compound Grifficyclocin B, a cyclic peptide with anti-tumor activity which was isolated from the plants of Goniothalamus species (Annonaceae). The bioassay results showed that these synthetic cyclopeptides exhibited different extent of cytotoxicity against human hepatocellular carcinoma cell lines. Among them, GG-8-6 (1) was the most active compound with IC50 values of 6.38 μM and 12.22 μM against SMMC-7721 and HepG2, respectively. Further studies on the mechanism demonstrated that GG-8-6 (1) could induce apoptosis and G2/M arrest of HCC cells, and the activation of caspase pathways was probably involved. In vivo anti-tumor experiments showed that GG-8-6 (1) could significantly inhibit the growth of tumor in the mouse xenograft tumor model. At the dose of 40 mg/kg, the inhibition ratio was 67.9% without weight loss. Our results suggested that GG-8-6 (1), a new cyclic peptide, might be a potential candidate for developing new anti-HCC drug in the coming future.

Graphical abstract

http://ift.tt/2zb1cq2

Induction of apoptosis by pyrazolo[3,4-d]pyridazine derivative in lung cancer cells via disruption of bcl-2/bax expression balance

Publication date: Available online 20 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mervat S. Mohamed, Abdou O. Abdelhamid, Fahad M. Almutairi, Ayat G. Ali, Mai K. Bishr
In the rapidly expanding era of cancer target therapy, regulators of apoptosis are emerging as attractive therapeutic targets. X-linked inhibitor of apoptosis (XIAP) is of specific interest owing to its characteristic overexpression in a wide variety of neoplasms, with a resultant survival advantage for tumor cells and treatment resistance. In this study, we examined three pyrazolo [3,4-d] pyridazine derivatives (PPDs) through molecular modeling and studied their modes of interaction with XIAP-BIR3 domain. PPD-1, which possessed the highest binding affinity with XIAP, was tested on A549 (lung cancer cell line); HCT-116 (colorectal carcinoma cell line); HEPG2 (liver carcinomacell line), HFB4 (normal human skin melanocyte cell line) and WI-38 (human embryonic lung fibroblasts). In comparison to cisplatin as a positive control, PPD-1 yielded remarkable cytotoxicity on all cancer cell lines, with the highest anti-tumor activity on A549 and a favorable therapeutic ratio. Flow cytometry studies concluded that PPD-1 treatment induces Sub G1 and G2/M cell cycle arrest and apoptosis. The percentage of apoptotic cells in PPD-1 treated A549 cells was considerably higher than that in untreated cells (10.06% vs 0.57%, respectively). To further investigate the mechanism of induction of apoptosis by PPD-1, Real time-PCR was used to quantify the expression levels of key apoptotic regulators. Significant overexpression of the effector capsase-3, pro-apoptotic bax and tumor suppressor gene p53 were noted as compared to untreated cells (7.19 folds, 7.28 folds, and 5.08 folds, respectively). Moreover, PPD-1 inhibited the expression of the anti-apoptotic bcl-2 gene to 0.22 folds. These findings demonstrate that PPD-1 treatment disrupts the Bcl-2/BAX balance in lung cancer cell lines, leading to apoptosis induction possibly through intrinsic mitochondria-dependent pathway. These novel insights elucidate the mechanism of PPD-1 cytotoxicity in lung cancer cell lines and offer a promising therapeutic approach that needs further study.

Graphical abstract

http://ift.tt/2zbORBE

Structure-Activity Relationships of Cryptopleurine Analogs with E-ring Modifications as Anti-Hepatitis C Virus Agents

Publication date: Available online 20 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ying Wang, Shao-Ru Chen, Xiaoming Yang, Kuo-Hsiung Lee, Yung-Chi Cheng
The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication.

Graphical abstract

http://ift.tt/2zbiROn

Oxytocin is present in islets and plays a role in beta-cell function and survival

Publication date: Available online 20 December 2017
Source:Peptides
Author(s): Shruti Mohan, Dawood Khan, R. Charlotte Moffett, Nigel Irwin, Peter R. Flatt
Oxytocin is associated mainly with modulating reproductive function. However, studies suggest that oxytocin also plays a role in endocrine pancreatic function. In the present study, islet expression of oxytocin and its related receptor was confirmed in mouse islets as well as cultured rodent and human beta-cells. Oxytocin significantly stimulated glucose-induced insulin secretion from isolated mouse islets. Similar insulinotropic actions were also observed in rodent BRIN BD11 and human 1.1B4 beta-cells. Positive effects of oxytocin on insulin secretion were almost fully annulled by the oxytocin receptor antagonist, atosiban. In terms of mechanism of insulin secretory action, oxytocin had no effect on beta-cell membrane potential or cAMP generation, but did augment intracellular calcium concentrations. In vivo administration of oxytocin to mice significantly reduced overall blood glucose levels and increased plasma insulin concentrations in response to a glucose challenge. Oxytocin also had a modest, but significant, appetite suppressive effect. As expected, streptozotocin diabetic mice had marked loss of beta-cell area accompanied by increases in alpha-cell area, whilst hydrocortisone treatment increased beta-cell and overall islet areas. Both mouse models of diabetes presented with dramatically decreased percentage islet oxytocin co-localisation with insulin and increased co-localisation of oxytocin. More detailed studies in cultured beta-cell lines revealed direct positive effects of oxytocin on beta-cell proliferation and protection against apoptosis. Together, these data highlight a potentially important role of islet-derived oxytocin and related receptor signalling pathways on the modulation of beta-cell function and survival.



http://ift.tt/2p4YBOx

Corrigendum to “Endothelial dysfunction mediated by interleukin-18 in patients with ischemic heart disease undergoing coronary artery bypass grafting surgery” [Med. Hypotheses 104 (2017) 20–24]

Publication date: February 2018
Source:Medical Hypotheses, Volume 111
Author(s): J. Sokolic, V. Sotosek Tokmadzic, D. Knezevic, I. Medved, N. Vukelic Damjani, S. Balen, M. Rakic, A. Lanca Bastiancic, G. Laskarin




http://ift.tt/2kU5FIB

Mirror neuron system activation in children with developmental coordination disorder: A replication functional MRI study

Publication date: Available online 21 December 2017
Source:Research in Developmental Disabilities
Author(s): J.E. Reynolds, J. Billington, S. Kerrigan, J. Williams, C. Elliott, A.M. Winsor, L. Codd, M. Bynevelt, M.K. Licari
BackgroundIt has been hypothesised that abnormal functioning of the mirror neuron system (MNS) may lead to deficits in imitation and the internal representation of movement, potentially contributing to the motor impairments associated with developmental coordination disorder (DCD).AimsUsing fMRI, this study examined brain activation patterns in children with and without DCD on a finger adduction/abduction task during four MNS activation states: observation; motor imagery; execution; and imitation.Methods and proceduresNineteen boys (8.25–12.75 years) participated, including 10 children with DCD (≤16th percentile on MABC-2; no ADHD/ASD), and nine typically developing controls (≥25th percentile on MABC-2).Outcomes and resultsEven though children with DCD displayed deficits behaviourally on imitation (Sensory Integration & Praxis Test Subtests) and motor imagery assessments prior to scanning, no differences in MNS activation were seen between the DCD and control groups at a neurological level, with both groups activating mirror regions effectively across conditions. Small clusters of decreased activation during imitation were identified in non-mirror regions in the DCD group, including the thalamus, caudate, and posterior cingulate − regions involved in motor planning and attentional processes.Conclusions and implicationsThe results of this study do not provide support for the MNS dysfunction theory as a possible causal mechanism for DCD. Further research to explore attentional and motor planning processes and how they may interact at a network level may enhance our understanding of this complex disorder.



http://ift.tt/2BUVEVW

The impact of iatrogenic glottic atresia due to photodynamic therapy for laryngeal cancer: A report of two cases

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Seiji Hosokawa, Satoru Takebayashi, Hiroyuki Mineta
Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment of premalignant and malignant diseases, including head and neck carcinomas. It can be applied before or after chemotherapy, irradiation, or surgery. Unlike irradiation and surgery, it can be repeated many times at the same site, and it is also associated with better cosmetic and functional outcomes [1]. We have treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we describe two such patients who developed vocal cord adhesion due to PDT. To our knowledge, there are no previous reports of patients with glottis atresia due to PDT, thus the cases reported herein are rare, and educationally valuable.



http://ift.tt/2p6kYmR

Effect of photodynamic and laser therapy in the treatment of peri-implant mucositis: A systematic review

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Abdulaziz M. Albaker, Aws S. ArRejaie, Mohammed Alrabiah, Tariq Abduljabbar
BackgroundThe present study systematically reviewed the literature to investigate the effect of photodynamic therapy (PDT) or laser therapy (LT) in the management of peri-implant mucositis (p-iM).MethodsThe electronic databases were searched until October 2017. Outcome measures were bleeding on probing (BOP), plaque index (PI), or probing depth (PD). The addressed PICO question was: "Is PDT and LT effective in the management of p-iM?"ResultsA total of five studies included in the qualitative analysis, two of which had a low risk of bias. Three studies used PDT while two studies used LT. All studies reported a significant improvement in clinical peri-implant inflammatory parameters in p-iM. For PDT, one study demonstrated a significant reduction for PDT group as compared to manual debridement (MD), while one study indicated comparable outcomes when tested with probiotics at follow-up. One study used PDT alone and indicated significant improvements in peri-implant parameters at follow-up. However, in the studies using LT, one study demonstrated a significant improvement in peri-implant parameters as compared to scaling and root planing alone, while other study indicated comparable outcomes when compared with manual debridement/chlorhexidine group at follow-up.ConclusionThis systematic review demonstrated inconclusive findings to show the effect of PDT or LT in the management of p-iM due to methodological heterogeneity such as non-standard control groups, laser parameters and short follow-up period. The results of this review should be considered preliminary and further, more robust, well-designed studies with long-term follow up and standardized comparators with laser parameters are warranted.



http://ift.tt/2p3nHgw

PHOTOTOXIC EFFECT OF ALUMINIUM-CHLORINE AND ALUMINIUM-HYDROXIDE PHTHALOCYANINES ON LEISHMANIA (L.) AMAZONENSIS

Publication date: Available online 21 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): V. Nesi-Reis, T.R. Navasconi, D.S.S.L. Lera-Nosone, E.L. Oliveira, P.M. Barbosa, W. Caetano, T.G.V. Silveira, S.M.A. Aristides, N. Hioka, M.V.C. Lonardoni
This study investigated the activity of photosensitive phthalocyanines on promastigotes and amastigotes of Leishmania (L.) amazonensis. Aluminum phthalocyanine chloride (AlPcCl), Aluminum phthalocyanine hydroxide (AlPcOH) and zinc phthalocyanine (PcZn) were tested in the presence (matte red LED, potency of 2.5–2.3 μW for 30 minutes) and absence of light against L. amazonensis promastigotes and the parasite viability was evaluated after 24, 48 and 72 h. The amastigote forms were treated with AlPcCl and AlPcOH, following the same lighting protocols described for the promastigote forms, being evaluated after 24 h. Cytotoxicity to human erythrocytes and peritoneal macrophages was also evaluated. The results showed that AlPcCl and AlPcOH in the presence of light have antileishmania activity, with leishmanistatic effects on promastigotes and amastigotes of L. amazonensis, without causing cytotoxicity to peritoneal macrophages and erythrocytes. The concentrations that inhibited 50% of the promastigote forms after 24 h of light exposure were 0.21 ± 0.08 μM for AlPcCl and 0.23 ± 0.06 μM for AlPcOH. In 48 h and 72 h after the treatment, the IC50 of AlPcCl was 0.13 ± 0.02 and 0.12 ± 0.03 μM and for AlPcOH was 0.14 ± 0.01 μM and 0.11 ± 0.01 μM, respectively. PcZn showed no activity on promastigotes of L. amazonensis. This study showed a substantial photodynamic activity of the phthalocyanines AlPcCl and AlPcOH against intracellular amastigotes forms of L. amazonensis after irradiation, presenting IC50 values of 0.62 ± 0.06 μM and 0.92 ± 0.12 μM, respectively. These results support the possibility of using photodynamic therapy for the treatment of cutaneous leishmaniasis.



http://ift.tt/2p3nqKw

Calcipotriol as pretreatment prior to daylight-mediated photodynamic therapy in patients with actinic keratosis: A case series

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Gaston Nestor Galimberti
This split-face design study evaluated the effect of pretreatment with calcipotriol prior to daylight-mediated photodynamic therapy (DL-PDT) in patients with actinic keratosis (AK).The study included 11 subjects with grade I–III AK (mean age: 55 years). Subjects used once-daily calcipotriol 50 mcg/g ointment on half the face/scalp for 15 days prior to DL-PDT. Evaluations of efficacy, safety and subject satisfaction were conducted 48 h and 7 days after treatment, and at 1- and 3-month follow-ups.Three months after treatment with calcipotriol/DL-PDT and DL-PDT alone, the complete response rate was 85% and 70%, respectively. The partial response rate was 12% and 25%, respectively. During calcipotriol pretreatment, 6 subjects reported erythema and moderate desquamation. In 7 subjects, calcipotriol/DL-PDT was associated with more marked erythema than that observed with DL-PDT alone. Eight subjects reported they preferred DL-PDT alone due to the inconvenience caused by the daily application of calcipotriol and the related erythema and desquamation.Although calcipotriol improved the efficacy of DL-PDT, it may not be applicable to all patients. DL-PDT is a simpler, safer and more convenient option than conventional-PDT. Therefore, the use of additional agents prolonging the course of treatment and increasing cost may diminish the advantages currently offered by DL-PDT.



http://ift.tt/2DmgMSS

Designing nickel base alloys for microstructural stability through low γ-γ′ interfacial energy and lattice misfit

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): S. Meher, M.C. Carroll, T.M. Pollock, L.J. Carroll
An extended stability alloy design strategy for multicomponent γ-γ′ nickel-base alloys with near-zero lattice misfit and as low as possible interfacial energy was investigated by isothermal annealing of two experimental alloys at 900°C for times up to 256h. The coarsening behavior of the spherical γ′ precipitates and the phase compositions determined by atom probe tomography were utilized to exploit a modified Lifshitz-Slyozov-Wagner relationship to estimate the interfacial energies. The estimated interfacial energies are much lower than predicted by a CALPHAD-based software as well as those typically reported for multicomponent γ-γ′ nickel alloys. Despite successfully minimizing the interfacial energy and γ-γ′ lattice misfit, these factors alone were not sufficient to impart high temperature extended stability through reduced coarsening kinetics.

Graphical abstract

http://ift.tt/2DnCJkq

Neutron interferometry detection of early crack formation caused by bending fatigue in additively manufactured SS316 dogbones

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Adam J. Brooks, Daniel S. Hussey, Hong Yao, Ali Haghshenas, Jumao Yuan, Jacob M. LaManna, David L. Jacobson, Caroline G. Lowery, Nikolay Kardjilov, Shengmin Guo, Michael M. Khonsari, Leslie G. Butler
Fatigue in selective laser melted (SLM) and conventionally manufactured stainless steel (SS) 316 dogbones was studied with neutron imaging methods for attenuation, diffraction, and scattering. Neutron attenuation tomography and Bragg edge imaging did not reveal crack formation. Conversely, to efficiently detect the microcrack evolution, two methods of grating-based neutron interferometry, Talbot-Lau and far-field, were employed. Both interferometry methods detect early crack formation via the dark-field (scattering) images, especially for porous microstructures in the range of 0.6μm to 2μm. The dark-field image combines sensitivity to micrometer-sized scattering centers at crack formation with sub-millimeter imaging resolution. The crack formation observed with neutron interferometry dark-field was validated post-imaging with additional fatigue cycles to fracture. Further inspection was performed by scanning electron microscopy (SEM) and optical photography. In the two fatigued dogbones, SLM and conventional crack formation was identified to within 1mm.

Graphical abstract

http://ift.tt/2DoqPHf

Multi-scale surface topography to minimize adherence and viability of nosocomial drug-resistant bacteria

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Jafar Hasan, Shubham Jain, Rinsha Padmarajan, Swathi Purighalla, Vasan K. Sambandamurthy, Kaushik Chatterjee
Toward minimizing bacterial colonization of surfaces, we present a one-step etching technique that renders aluminum alloys with micro- and nano-scale roughness. Such a multi-scale surface topography exhibited enhanced antibacterial effect against a wide range of pathogens. Multi-scale topography of commercially grade pure aluminum killed 97% of Escherichia coli and 28% of Staphylococcus aureus cells in comparison to 7% and 3%, respectively, on the smooth surfaces. Multi-scale topography on Al 5052 surface was shown to kill 94% of adhered E. coli cells. The microscale features on the etched Al 1200 alloy were not found to be significantly bactericidal, but shown to decrease the adherence of S. aureus cells by one-third. The fabrication method is easily scalable for industrial applications. Analysis of roughness parameters determined by atomic force microscopy revealed a set of significant parameters that can yield a highly bactericidal surface; thereby providing the design to make any surface bactericidal irrespective of the method of fabrication. The multi-scale roughness of Al 5052 alloy was also highly bactericidal to nosocomial isolates of E. coli, K. pneumoniae and P. aeruginosa. We envisage the potential application of engineered surfaces with multi-scale topography to minimize the spread of nosocomial infections.

Graphical abstract

http://ift.tt/2DnWOqK

Screw extrusion-based additive manufacturing of PEEK

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Jian-Wei Tseng, Chao-Yuan Liu, Yi-Kuang Yen, Johannes Belkner, Tobias Bremicker, Bernard Haochih Liu, Ta-Ju Sun, An-Bang Wang
Polyether-ether-ketone (PEEK) has high mechanical strength, thermal performance, and biocompatibility, and is widely used in biomedical and chemical engineering applications. However, to date there are no guidelines for the building of a 3D printer for highly viscous materials, e.g., PEEK. In this paper, a screw extrusion method was developed to overcome the existing problems of the filament-feeding method. Excellent flow stability (<3% variation) and high printing speed (up to 370mm/s) for PEEK printing were achieved. Highly reproducible mechanical tests of the printing products were demonstrated with 96% of the bulk material strength for the first time. Furthermore, an exchangeable printing head was built to cover both line- and plane-printing needs to widen its applications and improve printing surface quality (up to 0.945nm in Ra). All printed material had a more brittle character in comparison with the bulk material and the post annealing process was found to have no significant effect on the mechanical strength. Additionally, porous artificial intervertebral cages with controllable size and distribution were manufactured to demonstrate potential applications.

Graphical abstract

http://ift.tt/2DqGXYK

Effects of hot-deformation on grain boundary precipitation and segregation in Ti-Mo microalloyed steels

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Jiangting Wang, Peter D. Hodgson, Ilias Bikmukhametov, Michael K. Miller, Ilana Timokhina
Hot-deformation can refine grain size and change the dynamics of austenite-ferrite phase transformation during thermo-mechanical processing of microalloyed steels. Here, atom probe tomography has been used to characterize nanoscale precipitates and segregation in Ti-Mo microalloyed steels processed with and without hot-deformation at 890°C. It provides a comprehensive understanding of solute redistribution in both the grain interior and grain boundary regions. The results show that coarse (Ti, Mo)C precipitates are formed at grain boundaries, whereas fine precipitates are densely distributed in grain interiors, regardless of deformation conditions. Precipitate-free zones are developed near grain boundaries in the undeformed Ti-Mo steel, but absent in the hot-deformed steel. The elimination of precipitate-free zone in the hot-deformed steel is attributed to the high dislocation density and accelerated γ→α transformation caused by hot-deformation. The majority of Ti, Mo, and C atoms partition into (Ti, Mo)C precipitates, but Mn, Si, and Al atoms are mainly in solute state in ferrite matrix and segregation at grain boundaries. The hot-deformation significantly changes the C segregation at grain boundaries, but has little effect on other solute elements.

Graphical abstract

http://ift.tt/2Dqhm1W

Light driven fabrication of highly dispersed Mn-Co/RGO and the synergistic effect in catalytic degradation of methylene blue

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Xiu Liu, Lei Huang, Dengsong Zhang, Tingting Yan, Jianping Zhang, Liyi Shi
This work reports the synthesis of highly dispersed Mn-Co/RGO via a novel light driven approach having attributes of being green, facile and controllable, for the catalytic degradation of methylene blue (MB) in the presence of H2O2. The prepared catalysts were characterized by TEM, EDS, IR, XRD and XPS techniques. A synergy between RGO and Mn-Co species existed where the former helped in adsorption of MB and stabilization and dispersion of Mn and Co on the surface while the latter improved H2O2 utilization by generating HO, which enhanced the decomposition of MB. It was found that O2^•− and O2^•−/HO^• were the main radicals in post Mn/RGO and Mn-Co/RGO treatment, respectively. Both O2^•− and HO^• oxidized MB with a faster rate by the former, but its side reaction can hinder effective utilization of H2O2 while the reverse was true for the latter. A 50mg/LMB was completely decomposed within 15min using 10mg of Mn-Co/RGO. Thus the synergistic effect of RGO by adsorption MB and Co species avoiding the side reaction led to enhanced rate of MB decomposition.

Graphical abstract

http://ift.tt/2Dqh2jK

Thermal insulation characteristics of a lightweight, porous nanomaterial in high-temperature environments

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Haoyuan Ren, Dafang Wu, Junning Li, Wenjun Wu
Thermal-insulating nanomaterials with excellent thermal insulation performance are one type of thermal protection material used in spacecraft. In this study, the high-temperature insulation characteristics of a lightweight, porous aluminum oxide (Al2O3) nanomaterial were studied through experimentation using a self-developed thermal testing system for high-speed spacecraft, and were calculated by numerical simulation. The results showed that in a 1200°C front-surface, high-temperature environment, an Al2O3 nanomaterial sheet with a thickness of only 10mm could reduce the temperature by over 70% while exhibiting stable thermal insulation performance. This demonstrates that the Al2O3 nanomaterial has excellent high-temperature insulation performance. The scanning electron microscopy (SEM) images showed that, after the temperature exceeded 1200°C, the aggregation and growth of the Al2O3 nanoparticles accelerated, and single Al2O3 nanoparticles and voids increased significantly in size; in addition, the fibers inside the material started to melt, and the cracks started to increase considerably in number, depth, and width. Furthermore, a significant contraction and bending deformation occurred at the edges of the Al2O3 nanomaterial sheet; therefore, the Al2O3 nanomaterial is suitable for use in a thermal environment below 1200°C. The results provide an important reference basis for the design of thermal protection systems for spacecraft.

Graphical abstract

http://ift.tt/2DqgL0c

Compressive mechanical behavior of multiple wire metal rubber

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Jialin Hu, Qiang Du, Jinhai Gao, Jingyi Kang, Baoting Guo
This work presents the experimental characterization of multiple wire metal rubber material (MW-MR). MW-MR is a novel damping solid made of two kinds of coil entangled wires using a modified manufacturing process. Three batches of MW-MRs with different weight percentage ratios have been fabricated and tested under cyclic quasi-static loading and different maximum strains. Tangent modulus and loss factor are tested. The experimental results show that the weight percentage ratio can significantly affect the global mechanical compression properties. A microelement model of MW-MR was proposed for the first time, this model was based on the manufacturing process and then simplified by introducing the "equivalent factor" λ, a qualitative analysis based on the microelement model of MW-MR about the test results was made. The conclusions derived from the tests provide a new way for designers to adjust the mechanical properties of metal rubber.

Graphical abstract

http://ift.tt/2DnWKHw

Flexural fatigue behavior of thin laminated cementitious composites incorporating cenosphere fillers

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Asad Hanif, Muhammad Usman, Zeyu Lu, Yu Cheng, Zongjin Li
Flexural fatigue behavior of thin laminated cementitious composites (LCCs) is evaluated in this paper. LCCs were developed by incorporating fly ash cenosphere (FAC), as lightweight filler material, in various weight fractions of 40%, 50%, and 60%. The composites were reinforced with continuous reinforcement (welded wire mesh and woven glass fiber mesh), and discontinuous reinforcement (PVA fibers). Both single and double layer reinforced composites were cast. The developed composites were tested for static flexural strength as well as flexural fatigue strength under three – point flexural loading. The fatigue lives of LCC were determined at various stress levels and stress ratios. The results thus obtained are used to develop S-N relationships, and equations have been proposed to predict the flexural fatigue strength of LCC. The results indicate that the probabilistic distribution of fatigue life of LCC can be modeled by two-parameter Weibull distribution. The Weibull distribution has been employed to incorporate the failure probabilities into the fatigue life of LCC. The fatigue lives corresponding to different failure probabilities have been calculated and the data so obtained have been used to generate Pf-S-N diagrams. It is found that FAC is useful in producing structural lightweight composites with enhanced ductility and improved flexural fatigue characteristics.

Graphical abstract

http://ift.tt/2DrcdXw