Evidence for feasibility of fetal trophoblastic cell-based noninvasive prenatal testing

Abstract

Objective

The goal was to develop methods for detection of chromosomal and subchromosomal abnormalities in fetal cells in the mother's circulation at 10-16 weeks gestation using analysis by array comparative genomic hybridization (CGH) and/or next-generation sequencing (NGS).

Method

Nucleated cells from 30 ml of blood collected at 10-16 weeks gestation were separated from red cells by density fractionation and then immunostained to identify cytokeratin positive and CD45 negative trophoblasts. Individual cells were picked and subjected to whole genome amplification, genotyping, and analysis by array CGH and NGS.

Results

Fetal cells were recovered from most samples as documented by Y chromosome PCR, short tandem repeat analysis, array CGH, and NGS including over 30 normal male cells, one 47,XXY cell from an affected fetus, one trisomy 18 cell from an affected fetus, nine cells from a trisomy 21 case, three normal and one trisomy 13 cells from a case with confined placental mosaicism, and two chromosome 15 deletion cells from a case known by CVS to have a 2.7 Mb de novo deletion.

Conclusion

We believe that this is the first report of using array CGH and NGS whole genome sequencing to detect chromosomal abnormalities in fetal trophoblastic cells from maternal blood. This article is protected by copyright. All rights reserved.

http://ift.tt/2coyret

Markers associated with Alzheimer’s and Parkinson’s diseases are present in Mexico City children chronically exposed to concentrations of fine particulate matter PM2.5 above the current EPA USA standards

Mexico City (MC) children have lifetime exposures to concentrations of air pollutants above the current USA standards, including fine particulate matter (PM 2.5). Metropolitan Mexico City is an example of extreme urban growth and serious environmental pollution including high exposures to PM 2.5, ozone, polycyclic aromatic hydrocarbons (PAH), metals, endotoxins, tobacco smog, open waste dumps, highly polluting heavy duty trucks (not subjected to any pollution controls), etc., resulting in millions of children involuntarily exposed to harmful air neurotoxic substances every day since conception.

The results of this study including the significantly low concentrations of Aβ 1-42 and Brain-derived neurotrophic factor (BDNF) in MC children versus controls, suggests that major changes in key neural proteins playing major roles in neurotoxicity, cell survival, axonal and dendritic growth, and synaptic plasticity are evolving in urban MC children. Decreased levels of BDNF are associated with the development of obesity, depression, mood disorders, and neurodegeneration. Interestingly, Mexico City children increased their levels of total prion protein (TPrP) with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age. The low values of this key protein are likely detrimental given its protective effects against oxidative stress and its role in cell signaling, metal interactions, memory, myelin maintenance, axonal growth and neuronal development. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years, while the abnormal synuclein associated with Parkinson's disease exhibited a tendency to increase with cumulated PM2.5.

Mexico City children, teens, and young adults have shown a key marker of Alzheimer disease (AD): hyperphosphorylated tau along significant brain and intrathecal neuroinflammation, dysregulated immune responses, breakdown of epithelial and endothelial barriers, damage to the neurovascular unit, and brain accumulation of metals associated with combustion. Moreover, seemingly healthy children in Mexico City have olfaction deficits, dysregulation of feeding regulatory hormones, deficiencies in attention and short-term memory, and below-average scores in Verbal and Full Scale IQ compared to low air pollution children.

"Researchers are very concerned young Mexico City urbanites exhibit evidence of spectral markers of neurodegeneration that are often seen in adults with mild cognitive impairment, in Alzheimer patients and in mouse models of Alzheimer's disease" said Dr. Lilian Calderón-Garcidueňas.

"Our concern about Parkinson's disease is also increased when we observed children and teens with early autonomic dysfunction and in brainstem materials, extensive accumulation of α- synuclein in key nuclei including auditory nuclei and the dorsal nucleus of the vagus" said authors.

"These results add to growing data from our laboratory and others, suggesting urban residents with chronic high exposures to ozone and fine particulate matter have a higher risk for developing Alzheimer's disease (Jung et al., J Alzheimers Dis, 44, 573-584, 2015) and the potential key role of environmental magnetite nanoparticles in the brains of Mexico City residents (Maher et al., Proc Natl Acad Sci U S A, early edition) commented Dr. Calderón-Garcidueňas.

Air pollution is a serious public health issue and exposures to concentrations of air pollutants at or above the current standards have been clearly linked to neuroinflammation and neurodegeneration.

There is an urgent need for studying air pollution interactions impacting children's brains and their responses, which could provide new avenues for Alzheimer's and Parkinson's disease prevention.

The authors concluded: "We have a 50-year window of opportunity between the time urban children experience the detrimental effects we are describing here and when they will present with mild cognitive impairment, dementia, tremor or all of the above. Our efforts should be aimed to identify and mitigate environmental factors influencing the early development of neurodegenerative diseases and to neuroprotect high risk children. Unfortunately, to date there has been no support for studying the detrimental neurodegenerative effects of air pollution on the pediatric brain."

# # #

Contact:
Lilian Calderón-Garcidueňas, MA, MD, PhD
Biomedical Sciences
University of Montana
+1 406 243 4785
lilian.calderon-garciduenas@umontana.edu

NOTES FOR EDITORS
"Cerebrospinal fluid biomarkers in highly exposed PM2.5 urbanites: The risk of Alzheimer's and Parkinson's diseases in young Mexico City residents" by Lilian Calderón-Garcidueňas, José Avila-Ramírez, Ana Calderón-Garcidueñas, Tonatiuh González-Heredia, Hilda Acuña-Ayala, Chih-kai Chao, Charles Thompson, Rubén Ruiz- Ramos, Victor Cortés-González, Luz Martínez-Martínez, Mario Alberto García-Pérez, Jacques Reis, Partha S. Mukherjee, Ricardo Torres-Jardón, Ingolf Lachmann, J Alzheimers Dis 54, 597-613, 2016.

ABOUT THE JOURNAL OF ALZHEIMER'S DISEASE (JAD)
The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Published by IOS Press.

http://ift.tt/2cl5eU8

Efficacy and Safety of Crocus Sativus L in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

Scientists from the Aristotle University of Thessaloniki (AUTH), the Greek Association of Alzheimer's Disease and Related Disorders (GAADRD) and the Centre for Research and Technology Hellas/Information Technologies Institute (CERTH/ITI) have succeeded in making the shift to MCI therapy via robust natural remedies that can be used in order to forestall cognitive deterioration. In an article published in the Journal of Alzheimer's Disease, the researchers have indicated that 0,125 gr/ per day lead to better cognitive performance after 12 months as revealed in neuropsychological assessment, ERP response, and 3 Tesla MRI. P300 latency was measured by a HD-EEG [EGI 300 Geodesic EEG system (GES 300) using a 256-channel HydroCel Geodesic Sensor Net (HCGSN)]. A small volume increase on the left inferior temporal gyrus, an area close to medial temporal lobe (MTL) and hippocampus, was found in experimental group. Thus, this study highlighted how Crocus can change brain activation, striatal volume of specific brain regions, neuropsychological performance and cognitive processing in aMCI patients whereas control group exhibited worse performance after 12 months. Consequently, patients with MCI can hopefully have better cognitive functioning by taking Crocus Sativus L. on a daily basis.

It is widely known that no conventional or alternative therapy is currently available and approved to treat MCI patients. Current therapeutic strategies for cognitive impairment in AD, is symptomatic with cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine, galantamine, and the N-methyl-D-aspartate (NMDA) receptor antagonist memantine. The discovery of new natural compounds with neuroactive properties for the management of Neurodegenerative diseases (NDs) has gained much attention recently. Since no drug treatment is available to prevent the development of NDs, studies have shown that diet or plant-based extracts with antioxidant properties may have beneficial effects on improving brain function in NDs.

Nevertheless, preclinical and clinical pharmacological studies have demonstrated that Crocus sativus crude extracts and purified chemicals of it have anti-tumor effects, radical scavenging activity, anti-nociceptive and anti-inflammatory properties, inhibitory activity on Amyloid beta aggregation, reduce atherosclerosis and hepatic damage, counteract hyperlipidemia, protect from myocardial injury, display antihypertensive action, and finally it is safe and effective in mild to moderate AD as revealed from this study. More specifically, crocins and crocetin (molecules of Crocus sativus L.) have a wide range of activities including antioxidant effects, neuroprotective activities in memory impairment and antioxidant capacities. Also, crocin acts on NMDA receptors and on tracheal muscles β2-adrenoceptors, with a possible inhibitory effect on histamine (H1) receptors. More specifically, in vitro and in silico studies also suggest that crocetin can inhibit acetylcholinesterase, a main AD medicinal target.

Our study revealed in all measures we used better performance of treatment group compared with control group in the second assessment after 12 months of follow-up. Until today there is no other study which has proved that any kind of medication can be considered as an effective solution for patients with MCI. The same organizations are also focused on developing other novel pharmaceutical natural compounds that respond to a number of clinical needs in the effort against neurocognitive disorders.

*****

NOTES FOR EDITORS:
Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A, Georgiadis K, Tsolaki A, Adam K, Kompatsiaris I, Sinakos Z. J Alzheimers Dis. 2016 Jul 27;54(1):129-33. doi: 10.3233/JAD-160304. PMID: 27472878

Contact-Principal Investigator:
Magda Tsolaki
Professor of 3rd Department of Neurology, Aristotle University of Thessaloniki, Greece
Chair of Greek Federation of Alzheimer's disease in Greece
Scientific Director of Daily Alzheimer's centers in Thessaloniki, Greece
E-mail: tsolakim1@gmail.com
Tel: +306942918933, +302310234239
Fax: +30 2313 307332

About the Aristotle University of Thessaloniki (AUTH)
The Aristotle University of Thessaloniki is the largest university in Greece. It comprises 7 faculties that consist of 33 schools, 5 faculties that consist of one school each, as well as 4 independent schools. About 81,500 students study at the Aristotle University (72,140 in undergraduate programs and 8,360 in postgraduate programs). There are 2,150 faculty members: 739 professors, 435 associate professors, 634 assistant professors, and 342 lecturers. There are also 11 teaching assistants, 58 research fellows, 248 members of the Special Laboratory Teaching Personnel (S.L.T.P.), as well as 15 foreign language teachers and 4 foreign instructors. Faculty members are also assisted by 213 members of the Special Technical Laboratory Personnel (S.T.L.P.).

The Aristotle University of Thessaloniki conducts research projects, participates in European research programs, cooperates with international institutions and organizations and attracts outstanding researchers from within Greece and abroad. The Aristotle University supports research projects in a wide variety of disciplines related to the environment (natural and built), computing, new technologies and nanotechnology, telecommunications, industrial technologies, transport, biotechnology, biomedicine and health, agriculture, forestry and fishery, education and language, history and archaeology, social studies and economics.

About the Greek Association of Alzheimer's disease and Related Disorders (GAADRD)
The Greek Association of Alzheimer's Disease and Related Disorders is a non-profit organization that was founded in 1995 by relatives of patients suffering from Alzheimer's disease, doctors of all specialties (mainly neurologists and psychiatrists) and other experts (such as psychologists, social workers, physiotherapists, etc.) who deal with the problems caused by this disease and other types of dementia. The Association operates 2 day centers in Thessaloniki and has over 4.000 members. It is a member of Alzheimer Europe and Alzheimer's disease International (ADI) and has successfully participated in various national and European research projects producing new scientific knowledge and innovative interventions for cognitive disorders.

The aim of the Association is to offer information and advice concerning the care of patients with cognitive disorders and provide services for patients and their families. It also strives to offer help and support to caregivers in order to reduce the social, economic and emotional burden deriving from the long term care of people suffering from dementia. Lastly, the Association attempts to publicize the social needs of the affected population and inform the public on issues related to dementia and cognitive disorders in general.

About the Information Technologies Institute (ITI)-Centre for Research and Technology Hellas (CERTH)
The Information Technologies Institute, formerly Informatics and Telematics Institute, was established in 1998 in Thessaloniki as a non-profit research organization under the auspices of the General Secretariat of Research and Technology (GSRT) of the Greek Ministry of Development. Since 2000, ITI has joined the Centre for Research and Technology Hellas (CERTH). The main objective of the Institute is to be a research institution of excellence, identifying promising fields for the future and creating an environment that will allow the transfer of basic, applied and technological research in the growth of the digital economy of the 21st century. CERTH/ITI has developed spheres of excellence and critical mass in research and technology in several strategically important fields in a number of areas: Image and Signal Processing, Computer Vision, Human Computer Interaction, Virtual and Augmented Reality, Artificial Intelligence, Security and Surveillance, Biomedicine – Bioinformatics, Robotics, ICT for Environment Monitoring, Geosciences and Remote Sensing, Social Network Analysis, Networks and Communications, Cultural and Educational Technology.

About Journal of Alzheimer's disease (JAD)
The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 4.151 according to Thomson Reuters' 2014 Journal Citation Reports. The Journal is published by IOS Press.

——————————–
References
[1] Pitsikas N (2015) The effect of Crocus sativus L. and its constituents on memory: basic studies and clinical applications. Evid Based Complement Alternat Med 2015, 926284.
[2] Howe AS, Bani-Fatemi A, De Luca V (2014) The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer's disease. Brain Cogn 86, 64–74.

http://ift.tt/2cdEyYs

Midlife physical activity is associated with better cognition in old age

The association was studied first in all individuals of the cohort, and then by comparing later cognition in pairs where one twin was more physically active than the other.

Increasing the volume of physical activity was not, however, associated with increased memory-protecting benefits. Instead, quite a moderate amount of physical activity was found to be sufficient for memory-protecting benefits, and only the most inactive group of twins stood out with a significantly higher risk for cognitive impairment.

Overall, the study shows that moderately vigorous physical activity, meaning more strenuous than walking, is associated with better cognition after an average of 25 years.

This finding is in accordance with earlier animal model studies, which have shown that physical activity increases the amount of growth factors in the brain and improves synaptic plasticity.

The prevalence of dementia has increased with aging populations both in Finland and globally. Although the incidence of dementia seems to have decreased in less senior generations, the total prevalence of dementia is still expected to rise. No cure for dementia exists, but during the last decade research has produced an abundance of new information on dementia prevention. The traditional vascular risk factors (elevated blood pressure, hypercholesterolemia, obesity, diabetes and lack of exercise) have also been associated with dementia risk. However, few long-term, high-quality, follow-up studies on physical activity and cognition have been published, and it has remained unclear what type and amount of exercise is needed to safeguard cognition.

The study was conducted by scientists at the universities of Helsinki, Jyväskylä and Turku. The twins provided information on physical activity through questionnaire surveys from 1975 and 1981 (mean age in 1981: 49 years), while cognition was assessed by validated telephone interviews conducted between 1999 and 2015.

An early online version of this paper detailing the findings has been published. The full article is scheduled for publication in the 54(4) issue of the Journal of Alzheimer's Disease (Journal of Alzheimer's Disease 2016; 54(4), DOI 10.3233/JAD-160377).

Iso-Markku P, Waller K, Vuoksimaa E, Heikkilä K, Rinne J, Kaprio J, Kujala UM (2016) Midlife Physical Activity and Cognition Later in Life: A Prospective Twin Study. J Alzheimers Dis, DOI 10.3233/JAD-160377

Further information:
Researcher, M.D. Paula Iso-Markku, paula.iso-markku@helsinki.fi, tel. +358 50 428 4611
Professor Urho Kujala, urho.m.kujala@jyu.fi, tel. +358 40 805 3567

http://ift.tt/2cl6QwS

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

HEAD NECK

1.	ORIGINAL RESEARCH HEAD&NECK
	2016-01-01
	German National Library of Science and Technology (TIB)
2.	Head and neck cancer specialist offers us wonderful support.
	Green K 2016-08-01
	My husband Jerry was diagnosed with mouth cancer in January 2014 aged 45. A month later he went in for an operation and had a radical neck dissection. The floor of his mouth was replaced with skin from his forearm and part of his tongue was removed.
	Europe PubMed Central
3.	[Head and neck intensity-modulated radiation therapy: Normal tissues dose constraints. Pharyngeal constrictor muscles and larynx].
	Graff, P 2016-09-01
	PMID:27599684
	Science.gov (United States)
4.	[Treatment of head and neck squamous cell carcinoma recurrences and distant metastases : Highlights of the ASCO Meeting 2016].
	Bußmann, L 2016-09-01
	PMID:27604281
	Science.gov (United States)
5.	Searching beyond the usual papillomavirus suspects in squamous carcinomas of the vulva, penis and head andneck.
	Félez-Sánchez, Marta 2016-09-01
	PMID:27600594
	Science.gov (United States)
6.	Patients' experience of temporary tracheostomy after microvascular reconstruction for cancer of the head andneck.
	Rogers SN 2016-09-01
	A temporary tracheostomy is commonly done in patients who have reconstruction after the ablation of advanced oral cancer to provide easy access to a secure airway in case a haematoma forms or the patient needs a return to theatre. Although relatively simple to do, we know little about the patients' experience, and to find out, we designed a three-stage study. First, we conducted semi-structured interviews to identify items related to the functional, emotional, and social impacts of the tracheostomy, on the ward and on removal (n=15 patients). Secondly, we used these items to develop a short, one-page questionnaire in collaboration with the Patient and Carer Support Group and Research Forum, and thirdly, we did a cross-sectional postal survey of 125 patients who had had a temporary tracheostomy as part of free tissue reconstruction between January 2013 and July 2015. Of them, 86 responded (69% response rate). Generally patients reported a negative experience. In the cross-sectional survey most responders (n=52, 60%) stated that they would "very much" avoid a tracheostomy if at all possible. The main problems concerned fear and communication, and between one-third and one-half stated that they had had "very much" or "quite a bit" of a problem in regard to choking, discomfort, attracting attention, sleeping, and general management (other than the suctioning). This feedback should form part of the information that is given to patients; it should also enable us to reflect on optimal perioperative care, and help to inform the debate about the selection criteria.
	Europe PubMed Central
7.	Patients' experience of temporary tracheostomy after microvascular reconstruction for cancer of the head andneck.
	Rogers, S N 2016-09-01
	PMID:27596013
	Science.gov (United States)
8.	Immunohistochemical pattern analysis of squamous cell carcinoma: Lung primary and metastatic tumors ofhead and neck.
	Ichinose, Junji 2016-10-01
	PMID:27597287
	Science.gov (United States)
9.	Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer.
	Posch D 2016-01-01
	For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m(2)) plus cetuximab (500 mg/m(2)) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8-11.8) and 4.0 months (95% CI 1.0-7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted.
	Europe PubMed Central
10.	Sperm with fibrous sheath dysplasia and anomalies in head-neck junction: focus on centriole and centrin 1.
	Moretti, E 2016-09-01
	PMID:27596234
	Science.gov (United States)
11.	T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer.
	Beschel LM 2016-08-01
	Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity. In contrast, the frequency and absolute numbers of selected leukocyte subpopulations measured in samples of peripheral blood mononuclear cells (PBMCs) directly before the beginning of CRT were significantly different in patients with HGAOT as compared to those without. When we validated several potential markers including the abundance of T cells in a small prospective study with 16 HNSCC patients, we were able to correctly predict acute organ toxicity in up to 81% of the patients. We conclude that analysis of PBMCs by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing HGAOT caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome.
	Europe PubMed Central
12.	Mutational load and mutational patterns in relation to age in head and neck cancer.
	Meucci S 2016-08-01
	Head and neck squamous cell carcinoma (HNSCC) is a cancer with well-defined tumor causes such as HPV infection, smoking and drinking. Using The Cancer Genome Atlas (TCGA) HNSCC cohort we systematically studied the mutational load as well as patterns related to patient age in HNSCC. To obtain a homogenous set we excluded all patients with HPV infection as well as wild type TP53. We found that the overall mutational load is higher in patients of old age. Through unsupervised hierarchical clustering, we detected distinct mutational clusters in very young as well as very old patients. In the group of old patients, we identified four enriched pathways ("Axon Guidance", "ECM-Receptor Interaction", "Focal Adhesion" and "Notch Signaling") that are only sporadically mutated in the other age groups. Our findings indicate that the four pathways regulate cell motility, tumor invasion and angiogenesis supposedly leading to less aggressive tumors in older age patients. Importantly, we did not see a strict pattern of genes always mutated in older age but rather an accumulation of mutations in the same pathways. Our study provides indications of age-dependent differences in mutational backgrounds of tumors that might be relevant for treatment approaches of HNSCCs patients.
	Europe PubMed Central
13.	Mutational load and mutational patterns in relation to age in head and neck cancer.
	Meucci, Stefano 2016-08-16
	PMID:27596625
	Science.gov (United States)
14.	A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC).
	Guan, Jian 2016-09-01
	PMID:27602493
	Science.gov (United States)
15.	Chemoprevention of Head and Neck Squamous Cell Carcinoma (HNSCC) With Valproic Acid
	2016-09-05
	Head and Neck Squamous Cell Carcinoma
	Science.gov (United States)
16.	Safety of drug treatments for head and neck cancer.
	Galot R 2016-08-01
	The treatment of squamous cell carcinoma of the head and the neck depends on the disease's stage. In locally-advanced stage disease, multimodal treatment strategies, including surgery, radiotherapy and chemotherapy, give the best outcome in terms of overall survival. Those treatments are not without negligeable adverse events, which can lead to late debilitating toxicities. In recurrent/metastatic disease, not amenable to surgery or radiation therapy, palliative chemotherapy is the most appropriate treatment.This review aims to provide an overview of the safety of standard drug regimens used to treat SCCHN in daily practice, including platinum-based chemoradiation, induction chemotherapy, cetuximab and immunotherapy. The toxicities induced by single modality radiotherapy, or those resulting from surgery, are not part of the discussion.Toxicities observed with multimodal treatment of SCCHN are the highest we can tolerate in terms of treatment-related mortality, morbidity and late consequences. Patients at high risk of developing such complications should be identified upfront for optimal prevention and management. There is a medical need to identify less toxic regimens without compromising the treatment efficacy, especially for patients with Human Papilloma Virus-induced oropharyngeal cancers. Finally, it is crucial in future trials to better standardize the scales used to report treatment related adverse events.
	Europe PubMed Central
17.	Survival and Surgical Outcomes for Pediatric Head and Neck Melanoma.
	Richards, Morgan K 2016-09-01
	PMID:27607058
	Science.gov (United States)
18.	Electromyography and Mechanomyography Signals During Swallowing in Healthy Adults and Head and NeckCancer Survivors.
	Constantinescu G 2016-08-01
	Surface electromyography (sEMG) is used as an adjuvant to dysphagia therapy to demonstrate the activity of submental muscles during swallowing exercises. Mechanomyography (MMG) has been suggested as a potential superior alternative to sEMG; however, this advantage is not confirmed for signal acquired from submental muscles. This study compared the signal-to-noise ratio (SNR) obtained from sEMG and MMG sensors during swallowing tasks, in healthy participants and those with a history of head and neck cancer (HNC), a population with altered anatomy and a high incidence of dysphagia. Twenty-two healthy adults and 10 adults with a history of HNC participated in this study. sEMG and MMG signals were acquired during dry, thin liquid, effortful, and Mendelsohn maneuver swallows. SNR was compared between the two sensors using repeated measures ANOVAs and subsequent planned pairwise comparisons. Test-retest measures were collected on 20 % of participants. In healthy participants, MMG SNR was higher than that of sEMG for dry [t(21) = -3.02, p = 0.007] and thin liquid swallows [t(21) = -4.24, p < 0.001]. Although a significant difference for sensor was found in HNC participants F(1,9) = 5.54, p = 0.043, planned pairwise comparisons by task revealed no statistically significant difference between the two sensors. sEMG also showed much better test-retest reliability than MMG. Biofeedback provided as an adjuvant to dysphagia therapy in patients with HNC should employ sEMG technology, as this sensor type yielded better SNR and overall test-retest reliability. Poor MMG test-retest reliability was noted in both healthy and HNC participants and may have been related to differences in sensor application.
	Europe PubMed Central
19.	[Immunotherapeutic studies of head and neck tumors : Highlights of the 2016 ASCO Annual Meeting].
	Busch, C-J 2016-09-01
	PMID:27604282
	Science.gov (United States)
20.	Dose-volume analysis of radiation-induced trismus in head and neck cancer patients.
	Gebre-Medhin M 2016-09-01
	Trismus is a treatment-related late side effect in patients treated for cancer in the head and neck region (HNC). The condition can have a considerable negative impact on nutrition, dental hygiene, ability to speak and quality of life. We have previously studied trismus within the frame of a randomized phase 3 study of HNC patients treated with mainly three-dimensional (3D) conformal radiotherapy (CRT) and found a strong association to mean radiation dose to the mastication muscles, especially the ipsilateral masseter muscle (iMAS). In the present study we have investigated trismus prevalence and risk factors in a more recent cohort of patients, treated with todays' more updated radiation techniques.Maximal interincisal distance (MID) was measured on 139 consecutive patients. Trismus was defined as MID ≤35 mm. Patient-, disease- and treatment-specific data were retrospectively recorded. Differences between groups were analyzed and mean absorbed dose to mastication structures was evaluated. Dosimetric comparisons were made between this study and our previous results.The prevalence of trismus was 24% at a median of 16 months after completion of radiotherapy. In bivariate analysis treatment technique (3DCRT vs. intensity modulated radiotherapy or helical tomotherapy), tumor site (oropharynx vs. other sites) and mean radiation doses to the ipsilateral lateral pterygoid muscle, the paired masseter muscles and the iMAS were significantly associated with MID ≤35 mm. In multivariable analysis only mean radiation dose to the iMAS was significantly associated to MID ≤35 mm.Mean radiation dose to the ipsilateral masseter muscle is an important risk factor for trismus development. Dose reduction to this structure during radiotherapy should have a potential to diminish the prevalence of trismus in this patient group.
	Europe PubMed Central

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

IJERPH, Vol. 13, Pages 882: Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

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