[Primary research of early oral feeding after total laryngectomy].

PubMed

Huang, N; Zhu, Y M; An, C M; Liu, Y; Xu, Z G; Liu, S Y; Zhang, Z M

2018-06-07

Objective: To explore whether early oral feeding after total laryngectomy is safe and effective by evaluating the incidence of pharyngocutaneous fistula (PCF) and the hospital duration. Methods: A retrospective cohort study was conducted, including 52 patients underwent total laryngectomy, plus partial tongue base resection ( n =2), partial pharyngectomy ( n =1), or pedicle flap ( n =2) between January 2012 and October 2017. Patients who had a history of preoperative radiotherapy, chemotherapy or chemoradiotherapy, previous surgery for larynx or pharynx and who had severe complications were excluded. Early oral feeding started between 48 h and 72 h postoperatively, while delayed oral feeding started within postoperative day 8-10. The incidences of PCF in two groups were compared to evaluate whether PCF and early oral feeding was related. Multi-variables analysis was conducted to evaluate risk factors for PCF. Results: PCF rate was 19.2% among all patients, 11.1% in patients with early oral feeding and 23.5% in patients with delayed oral feeding. No significant statistically difference in PCF rate was found between two groups (χ(2)=0.506, P =0.477). Multi-variables analysis showed that oral feeding time (early or delayed) was not a independent risk factor of PCF (Two classification response variable Logistic regression, P =0.200, OR =0.242, 95% CI [0.028-2.118]). But low preoperative albumin level was observed as an independent risk factor for PCF ( P =0.039, OR =0.848, 95% CI [0.726-0.992]). A negative correlation was observed between preoperative albumin level and PCF. And also there was not a significant difference in hospital duration between patients with early oral feeding and delayed oral feeding( U =268, P =0.464). Conclusion: For patients total laryngectomy with no previous history of radiotherapy, chemotherapy, chemoradiotherapy, early oral feeding after surgery is safe and effective.

Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth

PubMed Central

Taniguchi, Masatomo; Tokumoto, Masanori; Tsuruya, Kazuhiko; Hirakata, Hideki; Iida, Mitsuo

2008-01-01

Background. Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. Methods. To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. Results. Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. Conclusions. These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism. PMID:18515308

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

PubMed

Kim, Da Hee; Seong, Seok Ju; Kim, Mi Kyoung; Bae, Hyo Sook; Kim, Mi La; Yun, Bo Seong; Jung, Yong Wook; Shim, Jeong Yun

2017-01-01

To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

The value of histological grading of biopsy and resection specimens in early stage oral squamous cell carcinomas.

PubMed

Dik, Eric A; Ipenburg, Norbertus A; Kessler, Peter A; van Es, Robert J J; Willems, Stefan M

2018-04-05

In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival. One-hundred and forty-five patients with OSCC staged as T1-2, N0 of the tongue, floor of mouth or cheek with primary resection of the tumor were examined. Biopsy and resection specimen were histologically re-assessed with regard to differentiation grade, as well as infiltrative, peri-neural and vascular invasive growth. This study showed a poor correlation between differentiation grade in the incisional biopsy and the resection specimen of the same tumor. No significant relation between differentiation grade of the resection specimen and nodal involvement, as well as overall and disease-specific survival was found. In early OSCC the differentiation grade determined by biopsy is of little predictive value for the grading of the resection specimen. Poor differentiation grade could not be related to the presence of nodal metastasis or survival and seems not to have any prognostic value concerning outcome. Treatment planning must be related to these findings. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

PubMed

Noorlag, Rob; Boeve, Koos; Witjes, Max J H; Koole, Ronald; Peeters, Ton L M; Schuuring, Ed; Willems, Stefan M; van Es, Robert J J

2017-02-01

Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017. © 2016 Wiley Periodicals, Inc.

Oral precancerous lesions: Problems of early detection and oral cancer prevention

NASA Astrophysics Data System (ADS)

Gileva, Olga S.; Libik, Tatiana V.; Danilov, Konstantin V.

2016-08-01

The study presents the results of the research in the structure, local and systemic risk factors, peculiarities of the clinical manifestation, and quality of primary diagnosis of precancerous oral mucosa lesions (OMLs). In the study a wide range of OMLs and high (25.4%) proportion of oral precancerous lesions (OPLs) in their structure was indicated. The high percentage of different diagnostic errors and the lack of oncological awareness of dental practitioners, as well as the sharp necessity of inclusion of precancer/cancer early detection techniques into their daily practice were noted. The effectiveness of chemilumenescence system of early OPLs and oral cancer detection was demonstrated, the prospects of infrared thermography as a diagnostic tool were also discussed.

A preliminary investigation into the morphology of oral papillae and denticles of blue sharks (Prionace glauca) with inferences about its functional significance across life stages.

PubMed

Rangel, Bianca de S; Wosnick, Natascha; Hammerschlag, Neil; Ciena, Adriano P; Kfoury Junior, José Roberto; Rici, Rose E G

2017-03-01

Sensory organs in elasmobranchs (sharks, skates, rays) detect and respond to a different set of biotic and/or abiotic stimuli, through sight, smell, taste, hearing, mechanoreception and electroreception. Although gustation is crucial for survival and essential for growth, mobility, and maintenance of neural activity and the proper functioning of the immune system, comparatively little is known about this sensory system in elasmobranchs. Here we present a preliminary investigation into the structural and dimensional characteristics of the oral papillae and denticles found in the oropharyngeal cavity of the blue shark (Prionace glauca) during embryonic development through adulthood. Samples were obtained from the dorsal and ventral surface of the oropharyngeal cavity collected from embryos at different development stages as well as from adults. Our results suggest that development of papillae occurs early in ontogeny, before the formation of the oral denticles. The diameter of oral papillae gradually increases during development, starting from 25 μm in stage I embryos, to 110 μm in stage IV embryos and 272-300 μm in adults. Embryos exhibit papillae at early developmental stages, suggesting that these structures may be important during early in life. The highest density of papillae was observed in the maxillary and mandibular valve regions, possibly related to the ability to identify, capture and process prey. The oral denticles were observed only in the final embryonic stage as well as in adults. Accordingly, we suggest that oral denticles likely aid in ram ventilation (through reducing the hydrodynamic drag), to protect papillae from injury during prey consumption and assist in the retention and consumption of prey (through adhesion), since these processes are only necessary after birth. © 2016 Anatomical Society.

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

PubMed Central

2017-01-01

Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

Are Stage of Change constructs relevant for subjective oral health in a vulnerable population?

PubMed

Jamieson, L M; Parker, E J; Broughton, J; Lawrence, H P; Armfield, J M

2015-06-01

Stage of Change constructs may be proxy markers of psychosocial health which, in turn, are related to oral health. To determine if Stage of Change constructs were associated with subjective oral health in a population at heightened risk of dental disease. Stage of Change constructs were developed from a validated 18-item scale and categorised into 'Pre-contemplative', 'Contemplative' and 'Active'. A convenience sample of 446 Australian non-Aboriginal women pregnant by an Aboriginal male (age range 14-43 years) provided data to evaluate the outcome variables (self-rated oral health and oral health impairment), the Stage of Change constructs and socio-demographic, behavioural and access-related factors. Factors significant at the p < 0.05 level in bivariate analysis were entered into prevalence regression models. Approximately 54% of participants had fair/poor self-rated oral health and 34% had oral health impairment. Around 12% were 'Pre-contemplative', 46% 'Contemplative' and 42% 'Active'. Being either 'pre-contemplative' or 'contemplative' was associated with poor self-rated oral health after adjusting for socio-demographic factors. 'Pre-contemplative' ceased being significant after adjusting for dentate status and dental behaviour. 'Pre-contemplative' remained significant when adjusting for dental cost, but not 'Contemplative'. The Stages of Change constructs ceased being associated with self-rated oral health after adjusting for all confounders. Only 'Contemplative' (reference: 'Active') was a risk indicator in the null model for oral health impairment which persisted after adding dentate status, dental behaviour and dental cost variables, but not socio-demographics. When adjusting for all confounders, 'Contemplative' was not a risk indicator for oral health impairment. Both the 'Pre-contemplative' and 'Contemplative' Stage of Change constructs were associated with poor self-rated oral health and oral health impairment after adjusting for some, but not all

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment

ClinicalTrials.gov

2018-03-02

Oral Cavity Neoplasm; Oropharyngeal Neoplasm; Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

The Oral Microbiome of Children: Development, Disease, and Implications Beyond Oral Health.

PubMed

Gomez, Andres; Nelson, Karen E

2017-02-01

In the era of applied meta-omics and personalized medicine, the oral microbiome is a valuable asset. From biomarker discovery to being a powerful source of therapeutic targets and to presenting an opportunity for developing non-invasive approaches to health care, it has become clear that oral microbes may hold the answer for understanding disease, even beyond the oral cavity. Although our understanding of oral microbiome diversity has come a long way in the past 50 years, there are still many areas that need to be fine-tuned for better risk assessment and diagnosis, especially in early developmental stages of human life. Here, we discuss the factors that impact development of the oral microbiome and explore oral markers of disease, with a focus on the early oral cavity. Our ultimate goal is to put different experimental and methodological views into perspective for better assessment of early oral and systemic disease at an early age and discuss how oral microbiomes-at the community level-could provide improved assessment in individuals and populations at risk.

The Oral Microbiome of Children: Development, Disease and Implications Beyond Oral Health

PubMed Central

Gomez, Andres; Nelson, Karen E.

2016-01-01

In the era of applied meta-omics and personalized medicine, the oral microbiome is a valuable asset. From biomarker discovery to being a powerful source of therapeutic targets, and to presenting an opportunity for developing non-invasive approaches to health care, it has become clear that oral microbes may hold the answer for understanding disease, even beyond the oral cavity. Although our understanding of oral microbiome diversity has come a long way in the past 50 years, there are still many areas that need to be fine-tuned for better risk assessment and diagnosis, especially in early developmental stages of human life. Here, we discuss the factors that impact development of the oral microbiome, and explore oral markers of disease, with a focus on the early oral cavity. Our ultimate goal is to put different experimental and methodological views into perspective for better assessment of early oral and systemic disease at an early age, and discuss how oral microbiomes- at the community level, could provide improved assessment in individuals, and populations at risk. PMID:27628595

Multimodality approach to optical early detection and mapping of oral neoplasia

NASA Astrophysics Data System (ADS)

Ahn, Yeh-Chan; Chung, Jungrae; Wilder-Smith, Petra; Chen, Zhongping

2011-07-01

Early detection of cancer remains the best way to ensure patient survival and quality of life. Squamous cell carcinoma is usually preceded by dysplasia presenting as white, red, or mixed red and white epithelial lesions on the oral mucosa (leukoplakia, erythroplakia). Dysplastic lesions in the form of erythroplakia can carry a risk for malignant conversion of 90%. A noninvasive diagnostic modality would enable monitoring of these lesions at regular intervals and detection of treatment needs at a very early, relatively harmless stage. The specific aim of this work was to test a multimodality approach [three-dimensional optical coherence tomography (OCT) and polarimetry] to noninvasive diagnosis of oral premalignancy and malignancy using the hamster cheek pouch model (nine hamsters). The results were compared to tissue histopathology. During carcinogenesis, epithelial down grow, eventual loss of basement membrane integrity, and subepithelial invasion were clearly visible with OCT. Polarimetry techniques identified a four to five times increased retardance in sites with squamous cell carcinoma, and two to three times greater retardance in dysplastic sites than in normal tissues. These techniques were particularly useful for mapping areas of field cancerization with multiple lesions, as well as lesion margins.

The role of lymphoscintigraphy, sentinel mode biopsy and positron emission tomography in the staging of the neck in early oral squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Hyde, Nicholas Charles

This thesis explores the limitations of current imaging modalities in the evaluation of the clinically node negative (N0) neck in early oral squamous cell carcinoma and evaluates the utility of two new interventions. It will become evident that the use of clinical parameters and conventional imaging to detect clinically occult cervical lymph node metastases is an imprecise science. The presence of metastases in the neck is the single most important determinant of survival. Hitherto the lack of timely intervention in this regard may have been contributory in amplifying their effect upon survival. There is an obvious requirement for a more accurate technique to stage the neck in this patient group. Therefore the application of lymphoscintigraphy in combination with sentinel node biopsy (SNB), and positron emission tomography (PET) have been investigated. It appears that PET, whilst having a number of useful roles in the generic head and neck oncology patient, has little to contribute in the diagnosis of occult neck disease. In contra-distinction lymphoscintigraphy and SNB are not only feasible in the diagnosis of occult metastases, but also enhance our knowledge of lymphatic drainage from the oral cavity. This has, in some circumstances, led to the modification of initially prescribed treatment plans. Such is the current pace of technological advance that over the course of this research an entirely new imaging modality has emerged - PET/CT. Whilst it has not been possible to apply this retrospectively to the original patient population early experience of this novel technique in head and neck malignancy is explored and reported. The results of these initial applications are encouraging.

Factors Influencing Early Detection of Oral Cancer by Primary Health-Care Professionals.

PubMed

Hassona, Y; Scully, C; Shahin, A; Maayta, W; Sawair, F

2016-06-01

The purposes of this study are to determine early detection practices performed by primary healthcare professionals, to compare medical and dental sub-groups, and to identify factors that influence the ability of medical and dental practitioners to recognize precancerous changes and clinical signs of oral cancer. A 28-item survey instrument was used to interview a total of 330 Jordanian primary health-care professionals (165 dental and 165 medical). An oral cancer knowledge scale (0 to 31) was generated from correct responses on oral cancer general knowledge. An early detection practice scale (0 to 24) was generated from the reported usage and frequency of procedures in oral cancer examination. Also, a diagnostic ability scale (0 to 100) was generated from correct selections of suspicious oral lesions. Only 17.8 % of the participants reported that they routinely performed oral cancer screening in practices. Their oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant positive correlation was found between knowledge scores and early detection practice scores (r = 0.22; p < 0.001). The diagnostic ability scores ranged from 11.5 to 96 with a mean of 43.6. The diagnostic ability score was significantly correlated with knowledge scores (r = 0.39; p < 0.001), but not with early detection practice scores (r = 0.01; p = 0.92). Few significant differences were found between medical and dental primary care professionals. Continuous education courses on early diagnosis of oral cancer and oral mucosal lesions are needed for primary health-care professionals.

A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition

PubMed Central

Paul, R R; Mukherjee, A; Dutta, P K; Banerjee, S; Pal, M; Chatterjee, J; Chaudhuri, K; Mukkerjee, K

2005-01-01

Aim: To describe a novel neural network based oral precancer (oral submucous fibrosis; OSF) stage detection method. Method: The wavelet coefficients of transmission electron microscopy images of collagen fibres from normal oral submucosa and OSF tissues were used to choose the feature vector which, in turn, was used to train the artificial neural network. Results: The trained network was able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. Conclusions: The results obtained from this proposed technique were promising and suggest that with further optimisation this method could be used to detect and stage OSF, and could be adapted for other conditions. PMID:16126873

Comparative performances of staging systems for early hepatocellular carcinoma.

PubMed

Nathan, Hari; Mentha, Gilles; Marques, Hugo P; Capussotti, Lorenzo; Majno, Pietro; Aldrighetti, Luca; Pulitano, Carlo; Rubbia-Brandt, Laura; Russolillo, Nadia; Philosophe, Benjamin; Barroso, Eduardo; Ferrero, Alessandro; Schulick, Richard D; Choti, Michael A; Pawlik, Timothy M

2009-08-01

Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

PubMed

Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

2016-12-01

An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European

Oral cancer. Practical prevention and early detection for the dental team.

PubMed

Kerr, A Ross; Cruz, Gustavo D

2002-01-01

Approximately 2,000 patients a year are diagnosed with oral cancer in New York State. In an effort to control this deadly disease, Governor George Pataki has taken a leadership role in the United States by mandating and funding training for dentists in the prevention and early detection of oral cancer. The purpose of this article is to highlight the epidemiology of oral cancer, to show how the dental profession can contribute to the health of the citizens of New York State, and to provide practical guidelines for both tobacco cessation intervention and utilization of existing technology for the early detection of oral cancer and precancerous conditions in the general dental practice setting.

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

PubMed

Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

2016-10-01

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage... Webinars regarding its proposed Early Stage Small Business Investment Companies (Early Stage SBIC) rule. The proposed Early Stage SBIC rule defines a new sub-category of small business investment companies...

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

PubMed

Frank, Jonathan M; Kayupov, Erdan; Moric, Mario; Segreti, John; Hansen, Erik; Hartman, Curtis; Okroj, Kamil; Belden, Katherine; Roslund, Brian; Silibovsky, Randi; Parvizi, Javad; Della Valle, Craig J

2017-01-01

Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Fridman, Eran; Na'ara, Shorook; Agarwal, Jaiprakash; Amit, Moran; Bachar, Gideon; Villaret, Andrea Bolzoni; Brandao, Jose; Cernea, Claudio R; Chaturvedi, Pankaj; Clark, Jonathan; Ebrahimi, Ardalan; Fliss, Dan M; Jonnalagadda, Sashikanth; Kohler, Hugo F; Kowalski, Luiz P; Kreppel, Matthias; Liao, Chun-Ta; Patel, Snehal G; Patel, Raj P; Robbins, K Thomas; Shah, Jatin P; Shpitzer, Thomas; Yen, Tzu-Chen; Zöller, Joachim E; Gil, Ziv

2018-05-14

Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Early stages of soldering reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lord, R.A.; Umantsev, A.

2005-09-15

An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with themore » theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.« less

Noninvasive detection and staging of oral cancer in vivo with confocal optoacoustic tomography

NASA Astrophysics Data System (ADS)

Savateeva, Elena V.; Karabutov, Alexander A.; Motamedi, Massoud; Bell, Brent A.; Johnigan, Richard M.; Oraevsky, Alexander A.

2000-05-01

Confocal opto-acoustic transducer (COAT) was developed and applied for detection of early stages of squamous cell carcinoma in hamster model of oral cancer. COAT is a novel imaging modality with optical and acoustic lens utilized for detecting in-depth opto-acoustic front surface transducer is an improved lateral resolution of 60-micrometers . The bandwidth of the confocal opto-acoustic transducer is more than 100 MHz. Therefore, in-depth axial resolution defined by the laser pulse duration and detection system equals 15-micrometers . Imaging was performed at the wavelength of the Nd:YAG laser second harmonic, which provided sufficient depth of monitoring and significant tissue contrast. Correlation of the opto- acoustic images with H and E histology sections in control animals and in animals treated with carcinogenic agent, DMBA, confirmed previous findings that early cancer lesions invisible by the naked eye may be detected with the opto- acoustic tomography. Compact design of COAT allows, in principle, application of the opto-acoustic imaging in any organ of the human digestive system.

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

PubMed Central

Gerritsen, Arja; Wennink, Roos A W; Besselink, Marc G H; van Santvoort, Hjalmar C; Tseng, Dorine S J; Steenhagen, Elles; Borel Rinkes, Inne H M; Molenaar, I Quintus

2014-01-01

Objective The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes. Methods An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake. Results The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods. Conclusions The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity. PMID:24308458

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

Oral Care for Developmentally Disabled Children: The Primary Dentition Stage.

ERIC Educational Resources Information Center

Kenny, David J.; Judd, Peter L.

1988-01-01

Developmental disabilities and chronic illness can impact the oral health of children in the preeruptive and primary dentition stages. The article covers prevention and management of dental caries; gingival changes; trauma to the primary dentition; sucking, swallowing, and mastication; extraorally fed patients; and factitial injuries. Home-care…

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Oral health content of early education and child care regulations and standards.

PubMed

Kranz, Ashley M; Rozier, R Gary

2011-01-01

Almost two out of every three US children younger than five receive child care from someone other than their parents. Health promotion in early education and child care (EECC) programs can improve the general health of children and families, but little is known about the role of these programs in oral health. We identified U.S. EECC program guidelines and assessed their oral health recommendations for infants and toddlers. State licensing regulations were obtained from the National Resource Center for Health and Safety in Child Care's online database. Professional standards were identified through a search of PubMed, early childhood organizations' websites, and early childhood literature. All EECC guidelines were reviewed for key terms related to oral health promotion in children and summarized by domains. Thirty-six states include oral health in their licensing regulations, but recommendations are limited and most often address the storage of toothbrushes. Eleven sets of standards were identified, four of which make recommendations about oral health. Standards from the American Academy of Pediatrics/American Public Health Association (AAP/APHA) and the Office of Head Start (OHS) provide the most comprehensive oral health recommendations regarding screening and referral, classroom activities, and education. Detailed guidelines for oral health practices exist but they exhibit large variation in number and content. States can use the comprehensive standards from the AAP/APHA and OHS to inform and strengthen the oral health content of their licensing regulations. Research is needed to determine compliance with regulations and standards, and their effect on oral health.

Oral Health Content of Early Education and Child Care Regulations and Standards

PubMed Central

Kranz, Ashley M.; Rozier, R. Gary

2012-01-01

Objective Almost two out of every three U.S. children younger than five receive child care from someone other than their parents. Health promotion in early education and child care (EECC) programs can improve the general health of children and families, but little is known about the role of these programs in oral health. We identified U.S. EECC program guidelines and assessed their oral health recommendations for infants and toddlers. Methods State licensing regulations were obtained from the National Resource Center for Health and Safety in Child Care’s online database. Professional standards were identified through a search of PubMed, early childhood organizations’ websites, and early childhood literature. All EECC guidelines were reviewed for key terms related to oral health promotion in children and summarized by domains. Results Thirty-six states include oral health in their licensing regulations, but recommendations are limited and most often address the storage of toothbrushes. Eleven sets of standards were identified, four of which make recommendations about oral health. Standards from the American Academy of Pediatrics/American Public Health Association (AAP/APHA) and the Office of Head Start (OHS) provide the most comprehensive oral health recommendations regarding screening and referral, classroom activities and education. Conclusions Detailed guidelines for oral health practices exist but they exhibit large variation in number and content. States can use the comprehensive standards from the AAP/APHA and OHS to inform and strengthen the oral health content of their licensing regulations. Research is needed to determine compliance with regulations and standards, and their effect on oral health. PMID:21070244

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

PubMed

Kılıç, Sarah S; Kılıç, Suat; Crippen, Meghan M; Varughese, Denny; Eloy, Jean Anderson; Baredes, Soly; Mahmoud, Omar M; Park, Richard Chan Woo

2018-04-01

Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. © 2018 Wiley Periodicals, Inc.

76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... respect to geographic location. SBA's primary concern in terms of geography is to ensure that the Early... SBICs is the primary source of cash used to service their SBA debt. SBA expects that some Early Stage...--Early Stage SBICs AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: In this...

Timetable for oral prevention in childhood--developing dentition and oral habits: a current opinion.

PubMed

Majorana, Alessandra; Bardellini, Elena; Amadori, Francesca; Conti, Giulio; Polimeni, Antonella

2015-01-01

As most of the etiologic factors of malocclusion are of genetic origin and thus cannot be prevented, environmental causative factors have become the focus for correction. Early interception of oral habits may be an important step in order to prevent occlusal disturbances in children. The identification of an abnormal habit and the assessment of its potential immediate and long-term effects on the dentition and potentially on the craniofacial complex should be made at an early stage. This paper focuses on the most common oral habits influencing dentofacial growth in childhood and management of these habits in the developing dentition.

Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

PubMed

Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

2013-04-01

The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Living with early-stage dementia: a review of qualitative studies.

PubMed

Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

2006-06-01

This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

A loss of profilin-1 in late-stage oral squamous cell carcinoma.

PubMed

Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

2017-08-01

The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photons from the early stages of relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

2017-07-01

We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis.

PubMed

Gadbail, Amol Ramchandra; Chaudhary, Minal; Gawande, Madhuri; Hande, Alka; Sarode, Sachin; Tekade, Satyajit Ashok; Korde, Sheetal; Zade, Prajakta; Bhowate, Rahul; Borle, Rajiv; Patil, Swati

2017-07-01

The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early writing deficits in preschoolers with oral language difficulties.

PubMed

Puranik, Cynthia S; Lonigan, Christopher J

2012-01-01

The purpose of this study was to investigate whether preschool children with language impairments (LI), a group with documented reading difficulties, also experience writing difficulties. In addition, a purpose was to examine if the writing outcomes differed when children had concomitant cognitive deficits in addition to oral language problems. A group of 293 preschool children were administered an assessment battery that included measures to examine oral language, nonverbal cognition, emergent reading, and writing. Children were divided into four groups based on their language and cognitive performance. The findings from this study show that as early as preschool, children with weaker oral language skills lag behind their peers with stronger oral language skills in terms of their writing-related skills. Children with oral language and cognitive deficits performed more poorly than children whose deficits were confined to oral language. A child's cognitive ability also has an impact on emergent writing skills, but it appears to be moderated by oral language skills. These results are consistent with research documenting links between preschool language and emergent reading in children with a history of LI. © Hammill Institute on Disabilities 2012.

Early Writing Deficits in Preschoolers with Oral Language Difficulties

PubMed Central

Puranik, Cynthia S.; Lonigan, Christopher J.

2016-01-01

The purpose of this study was to investigate whether preschool children with language impairments (LI), a group with documented reading difficulties, also experience writing difficulties. In addition, a purpose was to examine if the writing outcomes differed when children had concomitant cognitive deficits in addition to oral language problems. A group of 293 preschool children were administered an assessment battery that included measures to examine oral language, nonverbal cognition, emergent reading, and writing. Children were divided into four groups based on their language and cognitive performance. The findings from this study show that as early as preschool, children with weaker oral language skills lag behind their peers with stronger oral language skills in terms of their writing-related skills. Children with oral language and cognitive deficits performed more poorly than children whose deficits were confined to oral language. A child’s cognitive ability also has an impact on emergent writing skills, but it appears to be moderated by oral language skills. These results are consistent with research documenting links between preschool language and emergent reading in children with a history of LI. PMID:22043027

Current developments in the treatment of early-stage classical Hodgkin lymphoma.

PubMed

Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

2016-09-01

After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

Generic Difference Between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, Igor G.; Litvak, Maxim L.; Anfimov, Dimitrij S.; Sanin, Anton B.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey N.; Preece, Robert D.; Meegan, Charles A.

2001-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

General Differences between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, I. G.; Litvak, M. L.; Anfimov, D. S.; Sanin, A. B.; Briggs, M. S.; Paciesas, W. S.; Pendleton, G. N.; Preece, R. D.; Meegan, C. A.; Rose, M. Franklin (Technical Monitor)

2000-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

Vulnerability related to oral health in early childhood: a concept analysis.

PubMed

Mattheus, Deborah J

2010-09-01

This article is a report of the analysis of the concept of vulnerability and its relationship to oral health in early childhood. Poor oral health is a continued problem for children worldwide. Vulnerability increases the probability of poor oral health outcomes. The lack of clarity of the concept of vulnerability creates difficulty in understanding this multi-factoral condition. Data source included 34 articles covering the period 2000-2009 from a variety of disciplines, including nursing, dentistry, medicine and public health. The concept analysis was conducted using Rodgers' evolutionary method. The literature was analysed and a social ecology model was used to frame the discussion, recognizing family and community influences on children's oral health. The context of oral health in early childhood contributes to the changes in the concept vulnerability. The attributes are closely related to family and community factors and identified as limited parental income, parental education, community-based services and fluoride; and exposure to poor parental habits, parental neglect and harmful toxins. The primary antecedent is identified as a form of limited protection from exposure to various circumstances. Children with limited protection have increased vulnerability and greater probability of poor health outcomes. Nurses who understand the concept of vulnerability related to oral health and can identify factors that create protection and are capable of decreasing vulnerability through parent education, community awareness and policy changes that support children and families.

TWIST and p-Akt immunoexpression in normal oral epithelium oral dysplasia and in oral squamous cell carcinoma

PubMed Central

Yamamoto, Fernanda-Paula; Corrêa Pontes, Flávia-Sirotheau; Cury, Sérgio-Elias; Fonseca, Felipe-Paiva; Rebelo-Pontes, Hélder; Pinto-Júnior, Décio-dos Santos

2012-01-01

Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry. PMID:21743395

Measurement of salivary metabolite biomarkers for early monitoring of oral cancer with ultra performance liquid chromatography-mass spectrometry.

PubMed

Wang, Qihui; Gao, Pan; Cheng, Fei; Wang, Xiaoyi; Duan, Yixiang

2014-02-01

This study aimed to set-up an ultra performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) method for the determination of salivary L-phenylalanine and L-leucine for early diagnosis of oral squamous cell carcinoma (OSCC). In addition, the diagnostic accuracy for both biomarkers was established by using receiver operating characteristic (ROC) analysis. Mean recoveries of l-phenylalanine and L-leucine ranged from 88.9 to 108.6% were obtained. Intra- and inter-day precision for both amino acids was less than 7%, with acceptable accuracy. Linear regression coefficients of both biomarkers were greater than 0.99. The diagnostic accuracy for both biomarkers was established by analyzing 60 samples from apparently healthy individuals and 30 samples from OSCC patients. Both potential biomarkers demonstrated significant differences in concentrations in distinguishing OSCC from control (P<0.05). As a single biomarker, L-leucine might have better predictive power in OSCC with T1-2 (early stage of OSCC including stage I and II), and L-phenylalanine might be used for screening and diagnosis of OSCC with T3-4 (advanced stage of OSCC including stage III and IV). The combination of L-phenylalanine and L-leucine will improve the sensitivity (92.3%) and specificity (91.7%) for early diagnosis of OSCC. The possibility of salivary metabolite biomarkers for OSCC diagnosis is successfully demonstrated in this study. This developed method shows advantages with non-invasive, simple, reliable, and also provides lower detection limits and excellent precision and accuracy. These non-invasive salivary biomarkers may lead to a simple clinical tool for the early diagnosis of OSCC. © 2013 Published by Elsevier B.V.

Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study.

PubMed

Forte, Raimondo; Panzella, Lucia; Cesarano, Ida; Cennamo, Gilda; Eidenberger, Thomas; Napolitano, Alessandra

2017-01-01

The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone. © 2017 S. Karger AG, Basel.

Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy.

PubMed

Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

2015-01-01

Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers ( P <0.001). The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them.

Diversity Considerations for Promoting Early Childhood Oral Health: A Pilot Study

PubMed Central

Prowse, Sarah; Schroth, Robert J.; Wilson, Alexandria; Edwards, Jeanette M.; Sarson, Janet; Levi, Jeremy A.; Moffatt, Michael E.

2014-01-01

Objectives. Several groups in Manitoba, Canada, experience early childhood caries (ECC), including Aboriginal, immigrant, and refugee children and those from select rural regions. The purpose of this pilot study was to explore the views of parents and caregivers from four cultural groups on early childhood oral health and ECC. Methods. A qualitative descriptive study design using focus groups recruited parents and caregivers from four cultural groups. Discussions were documented, audio-recorded, transcribed, and then analyzed for content based on themes. Results. Parents and caregivers identified several potential barriers to good oral health practice, including child's temperament, finances, and inability to control sugar intake. Both religion and genetics were found to influence perceptions of oral health. Misconceptions regarding breastfeeding and bottle use were present. One-on-one discussions, parental networks, and using laypeople from similar backgrounds were suggested methods to promote oral health. The immigrant and refugee participants placed emphasis on the use of visuals for those with language barriers while Hutterite participants suggested a health-education approach. Conclusions. These pilot study findings provide initial insight into the oral health-related knowledge and beliefs of these groups. This will help to inform planning of ECC prevention and research strategies, which can be tailored to specific populations. PMID:24624141

Hepatocellular carcinoma: early-stage management challenges

PubMed Central

Erstad, Derek J; Tanabe, Kenneth K

2017-01-01

Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

A Four Stage Approach to Early Childhood Intervention.

ERIC Educational Resources Information Center

Haber, Julian S.

This paper describes a model for the involvement of primary health care personnel in the identification and treatment of developmental disabilities as a part of early childhood intervention programs. The integrated multidisciplinary model is divided into four stages. During the first stage an assignment of prenatal, perinatal, and postnatal risk…

Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs.

PubMed

Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup; Andersson, Sara B E; Artursson, Per; Beato, Stefania; Borde, Anders; Box, Karl; Brewster, Marcus; Dressman, Jennifer; Feng, Kung-I; Halbert, Gavin; Kostewicz, Edmund; McAllister, Mark; Muenster, Uwe; Thinnes, Julian; Taylor, Robert; Mullertz, Anette

2014-06-16

Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. Copyright © 2013 Elsevier B.V. All rights reserved.

Nuclear factor κB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma.

PubMed

Pontes, Hélder Antônio Rebelo; Pontes, Flávia Sirotheau Corrêa; Fonseca, Felipe Paiva; de Carvalho, Pedro Luiz; Pereira, Erika Martins; de Abreu, Michelle Carvalho; de Freitas Silva, Brunno Santos; dos Santos Pinto, Décio

2013-02-01

Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process. Copyright © 2013 Elsevier Inc. All rights reserved.

Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

PubMed Central

Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

2010-01-01

Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

Screening for Oral Cavity Cancer: A 1-year Experience of a Regional Hospital in Taiwan.

PubMed

Chi, T H; Yuan, C H; Chen, R F

2014-01-01

The purpose of this study was to analyze the risk factors affecting precancerous lesions, and cancer of oral cavity, and to assess efficacy of visual screening for oral mucosal lesions. The medical records of patients older than 30 years of age with history of habitual cigarette smoking or betel quid chewing that received screening for oral mucosal lesions between January 2012 and December 2012 were retrospectively reviewed. The patients' age, gender, risk factors, screening findings, and histopathology results of biopsy were included for further analysis. A total of 1341 patients were enrolled in this study. There were 1080 males and 261 females ranging from 30 to 96 years of age, with a mean age of 53.9±13.6 years. After screening, 226 (16.9%) were found to be positive of oral lesions. Among these 226 patients, 69 (30.5%) underwent biopsy under local anesthesia, and the histopathology showed malignancy in 13 (5.8%). All of the confirmed malignant cases were squamous cell carcinoma. Among them, 12 received further staging examination and one was lost to follow-up resulting in unknown stage. The early stage oral cavity cancer (stage I and II) accounted for 84.6% (11/13). The detection rate of early stage oral cavity cancer in our study was reasonable. Therefore, visual screening for oral cavity cancer is recommended for patients with habitual cigarette smoking or betel quid chewing.

Early stages of Ostwald ripening

NASA Astrophysics Data System (ADS)

Shneidman, Vitaly A.

2013-07-01

The Becker-Döring (BD) nucleation equation is known to predict a narrow double-exponential front (DEF) in the distribution of growing particles over sizes, which is due to early transient effects. When mass conservation is included, nucleation is eventually exhausted while independent growth is replaced by ripening. Despite the enormous difference in the associated time scales, and the resulting demand on numerics, within the generalized BD model the early DEF is shown to be crucial for the selection of the unique self-similar Lifshitz-Slyozov-Wagner asymptotic regime. Being preserved till the latest stages of growth, the DEF provides a universal part of the initial conditions for the ripening problem, regardless of the mass exchange mechanism between the nucleus and the matrix.

Influence of hope, social support, and self-esteem in early stage dementia.

PubMed

Cotter, Valerie T; Gonzalez, Elizabeth W; Fisher, Kathleen; Richards, Kathy C

2018-02-01

Background People in the early stages of dementia adjust to the illness through stages of awareness, coping, and evaluation. Studies have found that hope, social support, and self-esteem facilitate coping, adjustment, and adaptation in chronic illness. Objective The purpose of this descriptive study was to examine the relationships between hope, social support, and self-esteem in individuals with early stage dementia. Methods Data were obtained from 53 individuals with early stage dementia. The scores on the Herth Hope Index, Social Support Questionnaire Short-Form, and the State Self-Esteem Scale were analyzed using linear regression. Results Hope was moderately associated with self-esteem ( r = .49, p < .001). Hope accounted for 25% of the variance in self-esteem and was a key component in predicting self-esteem. No significant relationship was found between social support and self-esteem. Conclusion Findings suggest that hope may be an important factor to help individuals manage potential threats to self-esteem in the experience of early stage dementia. Strategies to inspire hope and then enhance self-esteem are promising for individuals living with early stage dementia.

Efficient harvesting methods for early-stage snake and turtle embryos.

PubMed

Matsubara, Yoshiyuki; Kuroiwa, Atsushi; Suzuki, Takayuki

2016-04-01

Reptile development is an intriguing research target for understating the unique morphogenesis of reptiles as well as the evolution of vertebrates. However, there are numerous difficulties associated with studying development in reptiles. The number of available reptile eggs is usually quite limited. In addition, the reptile embryo is tightly adhered to the eggshell, making it a challenge to isolate reptile embryos intact. Furthermore, there have been few reports describing efficient procedures for isolating intact embryos especially prior to pharyngula stage. Thus, the aim of this review is to present efficient procedures for obtaining early-stage reptilian embryos intact. We first describe the method for isolating early-stage embryos of the Japanese striped snake. This is the first detailed method for obtaining embryos prior to oviposition in oviparous snake species. Second, we describe an efficient strategy for isolating early-stage embryos of the soft-shelled turtle. © 2016 Japanese Society of Developmental Biologists.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

Usability of tablet computers by people with early-stage dementia.

PubMed

Lim, Fabian S; Wallace, Tim; Luszcz, Mary A; Reynolds, Karen J

2013-01-01

Tablet computers are generally associated with an intuitive interface. The adoption and use of tablet computers within the early-stage dementia context could potentially assist in daily living and provide users with a source for leisure activities and social networking. As dementia mainly affects the older adult population, it is expected that many people with dementia and even their carers do not use tablet computers as part of their everyday living. This paper explores the usability of tablet computers within the early-stage dementia context as a source of leisure for people with dementia. The main advantage of the use of tablet computers in this manner is to provide carers some reprieve from the constant care and attention often required in caring for people with dementia. Seven-day in-home trials were conducted to determine whether people with early-stage dementia were -capable of using a tablet computer independently. Twenty-one people with early-stage dementia and carer dyads participated in the trial. Feedback was gathered through questionnaires from both the person with dementia and their carer regarding the use of a tablet computer as part of their everyday living. Approximately half the participants with dementia were able to engage with and use the tablet computer independently, which proved to be helpful to their carers. No significant traits were observed to help identify those who were less likely to use a tablet computer. Carer relief was quantified by the amount of time participants with dementia spent using the device without supervision. The results and feedback from the trial provide significant insights to introducing new technology within the early-stage dementia context. Users' needs must be considered on a case-by-case basis to successfully facilitate the uptake of tablet computers in the dementia context. The trial has provided sufficient justification to further explore more uses of tablet computers in the dementia context, and not just for

Utility of PET-CT in detecting nodal metastasis in cN0 early stage oral cavity squamous cell carcinoma.

PubMed

Zhang, Han; Seikaly, Hadi; Biron, Vincent L; Jeffery, Caroline C

2018-05-01

Management of the clinically node-negative neck (cN0) in patients with early stage oral cavity squamous cell carcinoma (OCSCC) is challenging. Accurate imaging alternatives to elective neck dissections would help reduce surgical morbidity. While pooled studies suggest that imaging modalities have similar accuracy in predicting occult nodal disease, no study has examined the utility of PET-CT in this specific population of low-volume, clinically T1 and T2 OCSCC patients. A retrospective review of patients in the Alberta Cancer Registry who were diagnosed with cT1 or T2N0M0 OCSCC who underwent elective unilateral or bilateral neck dissections was performed. Pre-operative PET-CT and CT necks were reviewed for number of radiographically suspicious lymph nodes. Surgical pathology reports were reviewed to obtain the total number of nodes sampled and number of malignant nodes. Between 2009 and 2013, 148 patients were diagnosed with cT1 or T2N0M0 OCSCC. Of these, 96 patients underwent elective neck dissections. All patients underwent preoperative CT of the neck with 32 patients having undergone additional preoperative PET-CT. Based on finally surgical pathology, the overall rate of occult metastasis was 13.5% (13/96). The overall sensitivity and specificity of PET-CT in this cohort was 21.4% and 98.4%, respectively with a negative predictive value of 99.1%. Although sensitivity improved in patients with tumors ≥2 cm and depth ≥4 mm, specificity remained unchanged. In patients with cT1 and T2N0 OCSCC, PET-CT has high negative predictive value. These patients can be considered for treatment with single modality surgical resection and elective neck dissection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy

PubMed Central

Api, Murat; Kayatas, Semra; Boza, Aysen Telce; Nazik, Hakan; Adiguzel, Cevdet; Guzin, Kadir; Eroglu, Mustafa

2013-01-01

Background The aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer. Methods Retrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS. Results Seventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test). Conclusions There was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT. PMID:29147363

DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c. PROGRAM...determine the copy number gain and loss for early stage high grade ovarian cancers through IlluminaHumanOmniExpress-FFPE BeadChip system • Subtask 1 DNA

Management of Early Stage, High-Risk Endometrial Carcinoma: Preoperative and Surgical Considerations

PubMed Central

Pettigrew, Gaetan

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients. PMID:23878545

Multimodal imaging findings in 'hyper-early' stage MEWDS.

PubMed

Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

2017-10-01

To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

PubMed

Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

2016-12-29

The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

Driving behaviors in early stage dementia: a study using in-vehicle technology.

PubMed

Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

2012-11-01

According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bioaccumulation of lipophilic substances in fish early life stages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, G.I.; Kristensen, P.

1998-07-01

Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less

Immunohistochemical Expression of MCM-2 in Oral Epithelial Dysplasias.

PubMed

Zakaria, Samar H; Farag, Heba A; Khater, Dina S

2016-03-17

Oral cancer is one of the most frequent cancers in the world. It arises from epithelial dysplasia. Hence, identifying these lesions in an early stage could prevent their malignant transformation. The aim of the present work was to assess the cell proliferative activity of minichromosome maintenance protein (MCM-2) in oral epithelial dysplastic lesions and to correlate the results with different grades of epithelial dysplasia in an attempt to use MCM-2 in the early detection of malignancy. MCM-2 expression was determined by the nuclear count in a total of 30 oral epithelial dysplastic specimens roughly classified into 10 cases of mild, moderate, and severe dysplasia. Five cases of early invasive squamous-cell carcinomas and 5 cases of epithelial hyperplasia were also included. The MCM-2 immunostaining was found to increase gradually from mild to moderate to severe dysplasia and reached its maximum value in early invasive squamous cell carcinoma. MCM-2 is of prognostic value in cases of oral dysplasia that have a tendency to undergo malignant transformation.

Oral cancer prevention and early detection knowledge and practices of Illinois dentists--a brief communication.

PubMed

Lehew, Charles W; Kaste, Linda M

2007-01-01

The purpose of the study was to assess Illinois dentists' self-reported knowledge and practices concerning oral cancer prevention, early detection, and management as a baseline prior to conducting interventions designed to increase dentists' capacity to detect and manage oral cancers and counsel their patients about risk reduction. A weighted sample to represent licensed dentists in 19 counties yielded 518 dentists who responded to a 38-item mailed survey in 2004. Over 92 percent of the dentists reported providing oral cancer exams. However, many are not doing them properly or at frequent intervals. Over two-thirds had oral cancer continuing education, but 40 percent had it more than 2 years prior to the survey. Training in risk counseling was rare. Interventions are needed to assure appropriate skill and knowledge levels for oral cancer early detection, management, and risk counseling by Illinois dentists.

Effects of a Computer-Based Early Reading Program on the Early Reading and Oral Language Skills of At-Risk Preschool Children

ERIC Educational Resources Information Center

Huffstetter, Mary; King, James R.; Onwuegbuzie, Anthony J.; Schneider, Jenifer J.; Powell-Smith, Kelly A.

2010-01-01

This study examined the effects of a computer-based early reading program (Headsprout Early Reading) on the oral language and early reading skills of at-risk preschool children. In a pretest-posttest control group design, 62 children were randomly assigned to receive supplemental instruction with Headsprout Early Reading (experimental group) or…

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma

PubMed Central

Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius; Kiss, Katalin; Charabi, Birgitte; Specht, Lena; von Buchwald, Christian

2017-01-01

It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78–0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection. PMID:28212555

A multi-wavelength (u.v. to visible) laser system for early detection of oral cancer

NASA Astrophysics Data System (ADS)

Najda, S. P.; Perlin, P.; Leszczyński, M.; Slight, T. J.; Meredith, W.; Schemmann, M.; Moseley, H.; Woods, J. A.; Valentine, R.; Kalra, S.; Mossey, P.; Theaker, E.; Macluskey, M.; Mimnagh, G.; Mimnagh, W.

2015-03-01

A multi-wavelength (360nm - 440nm), real-time Photonic Cancer Detector (PCD) optical system based on GaN semiconductor laser technology is outlined. A proof of concept using blue laser technology for early detection of cancer has already been tested and proven for esophageal cancer. This concept is expanded to consider a wider range of wavelengths and the PCD will initially be used for early diagnosis of oral cancers. The PCD creates an image of the oral cavity (broad field white light detection) and maps within the oral cavity any suspicious lesions with high sensitivity using a narrow field tunable detector.

Balancing risk and benefit in early-stage classical Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas

2018-04-12

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.

Minimally invasive transcanal myringotomy for pediatric early stage congenital cholesteatoma.

PubMed

Jang, Chul Ho; Jung, Eun Kyung; Sung, Chung Man; Kim, Seung Beom; Kim, Young Yoon; Seong, Jong Yuap; Kang, Sung Hoon; Cho, Yong Beom

2016-11-01

Recently, minimally invasive transcanal myringotomy (MITM), which is a useful surgical technique for early stage congenital cholesteatoma (CC) in children, was introduced. The purpose of this study is to evaluate the short-term surgical results of MITM in pediatric early stage CC. We retrospectively reviewed the charts of 24 patients who underwent MITM between January 2013 and October 2015. The patients' ages ranged from 1 to 16 years (mean, 2.6 years). There were 17 male and 7 female patients. The right side (n = 13) was affected twice as often as the left side (n = 11). The most common site was the anterosuperior quadrant (15 cases). The diameter of the CC on axial computed tomography images ranged from 2.8 to 5.7 mm (mean, 3.9 mm). CCs were graded according to Potsic's system: 18 cases were classified as stage I, 3 case as stage II, and 3 cases as stage III. AllCCs except 1 were closed type. In21 patients, the tympanic membrane closed naturally without recurrence. Three patients showed small persistent dry perforation. Natural closure occurred in these patients, who were treated with paper patches. MITM is a simple, effective technique for removing an early stage CC from the middle ear, and it can minimize operative time, length of hospitalization, and postoperative morbidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.

PubMed

Foy, Jean-Philippe; Tortereau, Antonin; Caulin, Carlos; Le Texier, Vincent; Lavergne, Emilie; Thomas, Emilie; Chabaud, Sylvie; Perol, David; Lachuer, Joël; Lang, Wenhua; Hong, Waun Ki; Goudot, Patrick; Lippman, Scott M; Bertolus, Chloé; Saintigny, Pierre

2016-06-14

A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the areodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC.

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

PubMed

Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

2017-09-18

Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

TFM classification and staging of oral submucous fibrosis: A new proposal.

PubMed

Arakeri, Gururaj; Thomas, Deepak; Aljabab, Abdulsalam S; Hunasgi, Santosh; Rai, Kirthi Kumar; Hale, Beverley; Fonseca, Felipe Paiva; Gomez, Ricardo Santiago; Rahimi, Siavash; Merkx, Matthias A W; Brennan, Peter A

2018-04-01

We have evaluated the rationale of existing grading and staging schemes of oral submucous fibrosis (OSMF) based on how they are categorized. A novel classification and staging scheme is proposed. A total of 300 OSMF patients were evaluated for agreement between functional, clinical, and histopathological staging. Bilateral biopsies were assessed in 25 patients to evaluate for any differences in histopathological staging of OSMF in the same mouth. Extent of clinician agreement for categorized staging data was evaluated using Cohen's weighted kappa analysis. Cross-tabulation was performed on categorical grading data to understand the intercorrelation, and the unweighted kappa analysis was used to assess the bilateral grade agreement. Probabilities of less than 0.05 were considered significant. Data were analyzed using SPSS Statistics (version 25.0, IBM, USA). A low agreement was found between all the stages depicting the independent nature of trismus, clinical features, and histopathological components (K = 0.312, 0.167, 0.152) in OSMF. Following analysis, a three-component classification scheme (TFM classification) was developed that describes the severity of each independently, grouping them using a novel three-tier staging scheme as a guide to the treatment plan. The proposed classification and staging could be useful for effective communication, categorization, and for recording data and prognosis, and for guiding treatment plans. Furthermore, the classification considers OSMF malignant transformation in detail. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

PubMed

Sun, Da-Li; Li, Wei-Ming; Li, Shu-Min; Cen, Yun-Yun; Xu, Qing-Wen; Li, Yi-Jun; Sun, Yan-Bo; Qi, Yu-Xing; Lin, Yue-Ying; Yang, Ting; Lu, Qi-Ping; Xu, Peng-Yuan

2017-02-10

Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001). The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal

OC28 - Effect of mode of delivery on early oral colonization and childhood dental caries: a systematic review.

PubMed

Antão, Celeste; Teixeira, Cristina; Gomes, Maria José

2016-05-09

Theme: Multidisciplinary team working. Oral colonization starts at birth by vertical transmission. To determine whether mode of delivery influences the oral colonization of infants and contributes to the risk of childhood dental caries. A systematic review was conducted in the electronic database Web of Science for articles published from January 1995 to December 2015 by using a set of keywords. From 2,644 citations identified through electronic search, ten studies met the inclusion criteria. According to the studies mode of delivery influences oral microbial density, oral microbial profile and the timing of oral colonization by cariogenic microbiota. However, there are no consistent results concerning either the prevalence of children harboring cariogenic microbiota or the prevalence of early childhood caries by mode of delivery. Mode of delivery influences early oral colonization. However, it seems that other determinants rather than mode of delivery could be major contributors to the development of early childhood caries.

Oral manifestations as an early clinical sign of acute myeloid leukaemia: a case report.

PubMed

Guan, G; Firth, N

2015-03-01

Leukaemia is the most common malignancy in children and one of the most common malignancies in young adults. Acute myeloid leukaemia is often associated with early oral manifestations. The purpose of this study is to report the case of a 49-year-old male with spontaneous gingival bleeding for over two years with undiagnosed leukaemia. Haematological investigation was instigated and on referral to the Haematology Department at Dunedin Public Hospital, the diagnosis of an acute myeloid leukaemia was confirmed. Since oral lesions can be one of the early events of acute myeloid leukaemia, they may be considered as an important diagnostic indicator for oral health practitioners, and their roles in diagnosing and treating such patients. © 2015 Australian Dental Association.

Freeze-Dried Black Raspberries in Preventing Oral Cancer Recurrence in High-Risk Appalachian Patients Previously Treated With Surgery For Oral Cancer

ClinicalTrials.gov

2018-03-04

Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

PubMed Central

2014-01-01

Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia.

PubMed

Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun

2014-03-21

Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.

Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

PubMed

Nanayakkara, P G C L; Dissanayaka, W L; Nanayakkara, B G; Amaratunga, E A P D; Tilakaratne, W M

2016-04-01

The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early intensive rehabilitation after oral cancer treatment.

PubMed

Bschorer, Maximilian; Schneider, Daniel; Hennig, Matthias; Frank, Bernd; Schön, Gerhard; Heiland, Max; Bschorer, Reinhard

2018-06-01

The treatment of oral cancer requires an effective rehabilitation strategy such as an early intensive rehabilitation (EIR) program. The medical records and data of 41 patients who participated in an EIR program and 20 control group patients were analyzed. These patients all underwent surgical resection of the primary tumor followed by microsurgical reconstruction using free flaps. The length of stay (LOS) at the acute care hospital was compared between the two groups. Four indexes were used to evaluate the effectiveness of the EIR program. EIR patients stayed an average of 11.6 fewer days at the acute care hospital. All indexes showed significant improvements (p < 0.001). The Barthel Index (BI) and the Early Intensive Rehabilitation Barthel Index (EIR-BI) improved by 36.0 and 103.6 points, respectively. At discharge, the Bogenhausener Dysphagia Score (BODS) had improved to a score of 11.0 compared to the 13.9 at admission. EIR patients had a Work Ability Index (WAI) score of 25.7. Length of stay at the acute care hospital can be reduced using early intensive rehabilitation if patients are transferred to an intensive rehabilitation clinic early. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

PubMed

De Santis, R J; Poon, I; Lee, J; Karam, I; Enepekides, D J; Higgins, K M

2016-08-02

The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (�

Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

PubMed

He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

2017-12-01

This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

Oral Cancer Knowledge and Awareness in Patients Visiting Kantipur Dental College.

PubMed

Bajracharya, Dipshikha; Gupta, Sujaya; Sapkota, Manish; Bhatta, Shishir

2018-01-01

Lack of knowledge and awareness about oral cancer, its risk factors and negligence of the early warning signs play crucial role in raising the incidence of the disease. The present study was carried out to evaluate the awareness of oral cancer among patients visiting Kantipur Dental College, Kathmandu, Nepal. The cross-sectional study was done in 471 patients from 15-85 years. Self administered questionnaire was prepared which comprised of knowledge of oral cancer, source of information, its early signs and symptoms along with the awareness of its risk factors. Most of the participants (41.80%) had not heard of oral cancer. 31.60% recognized tobacco smoking and tobacco chewing as the chief risk factor with 15.50% and 10.80% of participants who identified white patch and red patch as early sign of oral cancer respectively. Pearson's chi square test was used which showed statistically significant association of total mean knowledge score and awareness score with age, education level and occupation (p<0.05). This study done in dental patients showed lack of knowledge and awareness in general public about oral cancer. There seem to be a need for more planned awareness programs through newspapers, radio, television and health campaigns regarding the association of habits in the development of oral cancer and benefits of detecting oral cancer at early stage for better prognosis.

Three-peat NREL Intern Pushes Boundaries of Early-Stage Fuels Research on

Science.gov Websites

Early-Stage Fuels Research on Way to Master's Degree Three-peat NREL Intern Pushes Boundaries of Early -Stage Fuels Research on Way to Master's Degree January 4, 2018 Woman preparing a fuel evaluation in a constant volume combustion vessel Drew Cameron, Research Participant Program Intern, prepares a test for

Urine biomarkers in the early stages of diseases: current status and perspective.

PubMed

Jing, Jian; Gao, Youhe

2018-02-01

As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population

PubMed Central

Dantas, Thinali Sousa; de Barros Silva, Paulo Goberlânio; Sousa, Eric Fernandes; da Cunha, Maria do PSS; de Aguiar, Andréa Silvia Walter; Costa, Fábio Wildson Gurgel; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu

2016-01-01

Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID:26817864

Early childhood experiences, cultural beliefs, and oral health of Mexican American women.

PubMed

Miltiades, Helen B

2013-01-01

This qualitative article examines how financial resources, cultural beliefs, and early childhood experiences affect perceptions of oral health and dental utilization of middle-aged and older Mexican American women. Fourteen in-depth qualitative interviews were conducted. The women's ages range from 49 to 87 years. Most had not visited the dentist in more than 2 years. Most women's early childhood experiences did not include dental visits or dental instruction. Some believed tooth loss was a normal aging process. Misconceptions regarding preventive care, the belief that dental visits were only necessary when experiencing pain, and finances were the primary reasons for not visiting the dentist. The results lend insight into the oral health, self-care practices, and dental utilization of middle-aged and older immigrant Mexican American women.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Early-stage valuation of medical devices: the role of developmental uncertainty.

PubMed

Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

2010-08-01

At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

Changes in health-related quality of life of oral cancer patients treated with curative intent: experience of a developing country.

PubMed

Doss, J G; Ghani, W M N; Razak, I A; Yang, Y H; Rogers, S N; Zain, R B

2017-06-01

This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ 2 test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment modality. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Pre-treatment HRQOL scores were significantly lower for late than early stage patients. At 1 month post-treatment, the functional and head and neck domains and the FACT-H&N (TOI) summary scores showed significant deterioration in both early and late stage patients. In contrast, the emotional domain showed a significant improvement for early and late stage patients at 1, 3, and 6 months post-treatment. Although HRQOL deterioration was still observed among early and late stage patients at 6 months post-treatment, this was not statistically significant. In conclusion, advanced disease is associated with poorer HRQOL. Although ethnic differences were observed across different disease stages, the influence of ethnicity on patient HRQOL was not evident in this study. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Impact of early childhood caries on oral health-related quality of life of preschool children.

PubMed

Li, M Y; Zhi, Q H; Zhou, Y; Qiu, R M; Lin, H C

2015-03-01

Child oral health-related quality of life (COHRQoL) has been assessed in developed areas; however, it remains unstudied in mainland China. Studies on COHRQoL would benefit a large number of children in China suffering from oral health problems such as dental caries. This study explored the relationship between COHRQoL and early childhood caries, adjusted by socioeconomic factors, in 3- to 4-year-old children in a region of southern China. In this study, 1062 children aged 3-4 years were recruited by cluster sampling and their oral health statuses were examined by a trained dentist. The Chinese version of the Early Childhood Oral Health Impact Scale (ECOHIS) and questions about the children's socioeconomic conditions were completed by the children's parents. A negative binomial regression analysis was used to assess the prevalence of early childhood caries among the children and its influence on COHRQoL. The total ECOHIS scores of the returned scale sets ranged from 0 to 31, and their average scores was 3.1±5.1. The negative binomial analysis showed that the dmfs indices were significantly associated with the ECOHIS score and subscale scores (P<0.05). The multivariate adjusted model showed that a higher dmft index was associated with greater negative impact on COHRQoL (RR = 1.10; 95% CI = 1.07, 1.13; P < 0.05). However, demographic and socioeconomic factors were not associated with COHRQoL (P>0.05). The severity of early childhood caries has a negative impact on the oral health-related quality of life of preschool children and their parents.

[The origin of hydrogen peroxide in oral cavity and its role in oral microecology balance].

PubMed

Keke, Zhang; Xuedong, Zhou; Xin, Xu

2017-04-01

Hydrogen peroxide, an important antimicrobial agent in oral cavity, plays a significant role in the balance of oral microecology. At the early stage of biofilm formation, about 80% of the detected initial colonizers belong to the genus Streptococcus. These oral streptococci use different oxidase to produce hydrogen peroxide. Recent studies showed that the produced hydrogen peroxide plays a critical role in modulating oral microecology. Hydrogen peroxide modulates biofilm development attributed to its growth inhibitory nature. Hydrogen peroxide production is closely associated with extracellular DNA(eDNA) release from microbe and the development of its competent cell which are critical for biofilm development and also serves as source for horizontal gene transfer. Microbe also can reduce the damage to themselves through several detoxification mechanisms. Moreover, hydrogen peroxide is also involved in the regulation of interactions between oral microorganisms and host. Taken together, hydrogen peroxide is an imperative ecological factor that contributes to the microbial equilibrium in the oral cavity. Here we will give a brief review of both the origin and the function in the oral microecology balance of hydrogen peroxide.

Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis.

PubMed

Gong, Xiaohui; Xu, Xiaojuan; Lin, Sisi; Cheng, Yu; Tong, Jianhua; Li, Yongyu

2017-08-01

The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.

To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study.

PubMed

Gupta, Karan; Panda, Naresh K; Bakshi, Jaimanti; Das, Ashim

2015-01-01

Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM) staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of the same on survival. Retrospective chart review from year 2007 to 2013, at a tertiary care center. All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA). Disease-free survival curves were generated using Kaplan-Meier algorithm. One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2%) were males and 48 (37.8%) females with a mean age at presentation 43.6 years (29-79 years). The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Correlation of serum biomarkers (TSA & LSA) and epithelial dysplasia in early diagnosis of oral precancer and oral cancer.

PubMed

Sawhney, Hemant; Kumar, C Anand

Oral cancer is currently the most frequent cause of cancer-related deaths, which is usually preceded by oral pre-cancerous lesions and conditions. Altered glycosylation of glycoconjugates, such as sialic acid, fucose, etc. are amongst the important molecular changes that accompany malignant transformation. The purpose of our study was to evaluate usefulness of serum Total Sialic Acid (TSA) and serum Lipid-Bound Sialic Acid (LSA) as markers of oral precancerous lesions and histopathologically correlating them with grades of epithelial dysplasia. Blood samples were collected from 50 patients with oral precancer (Leukoplakia & OSMF), 25 patients with untreated oral cancer and 25 healthy subjects. Serum sialic acid (total and lipid bound) levels were measured spectrophotometrically. Tissue samples from all the patients were evaluated for dysplasia. Serum levels of total and lipid bound sialic acid were significantly elevated in patients with oral precancer and cancer when compared with healthy subjects. Analysis of variance test documented that there is progressive rise in serum levels of sialic acid with the degree of dysplastic changes in oral precancer patients. We observed positive correlation between serum levels of the markers and the extent of malignant disease (TNM Clinical staging) as well as histopathological grades. The results suggested that serum levels of TSA and LSA progressively increases with grades of dysplasia in precancerous groups and cancer group, when compared with healthy controls. These glycoconjugates, especially LSA has the clinical utility in indicating a premalignant change.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Oral misoprostol versus oxytocin in the management of the third stage of labour.

PubMed

Parsons, Steven M; Walley, Robert L; Crane, Joan M G; Matthews, Kay; Hutchens, Donna

2006-01-01

To compare the effects of oral misoprostol 800 mug with intramuscular oxytocin 10 IU in routine management of the third stage of labour. This randomized controlled trial was performed in a rural district hospital in Ghana, West Africa, and enrolled women in labour with anticipated vaginal delivery and no known medical contraindication to prostaglandin administration. Women were randomized to receive oral misoprostol 800 mug or intramuscular oxytocin 10 IU. Blood samples were taken to determine hemoglobin concentration before delivery and at 12 hours post partum. Treatment was administered at delivery of the anterior shoulder. The primary outcome was the change in hemoglobin concentration from before to after delivery. Secondary outcomes included other measures of blood loss and presumed medication side effects. In total, 450 women were enrolled in the study. Their baseline characteristics were similar. There was no significant difference between the groups in the change in hemoglobin concentration (misoprostol 1.07 g/dL and oxytocin 1.00 g/dL). The only significant secondary outcomes were shivering (80.7% with misoprostol vs. 3.6% with oxytocin) and pyrexia (11.4% with misoprostol, none with oxytocin). Routine use of oral misoprostol 800 microg appears to be as effective as 10 IU parenteral oxytocin in minimizing blood loss during the third stage of labour, as determined by change in hemoglobin concentration. Misoprostol appears to be a safe, inexpensive, and effective uterotonic for use in rural and remote areas, where intravenous oxytocin may be unavailable.

Feasibility of a Clinical Pathway with Early Oral Intake and Discharge for Laparoscopic Gastrectomy.

PubMed

Nakagawa, M; Tomii, C; Inokuchi, M; Otsuki, S; Kojima, K

2017-12-01

Although some studies have reported the safety of early oral intake after gastrectomy, it still remains controversial. This study focused on the feasibility of a clinical pathway with early oral intake and discharge setting for exclusively laparoscopic distal gastrectomy. A clinical pathway was applied to 403 patients until December 2014. In the protocol, patients are allowed to take a sip of water and a soft diet on the first and second days after the operation, respectively, and the discharge day is set as the fifth to seventh day after the operation. Clinicopathological variables were prospectively collected, and risk factors for discharge variances were analyzed. The completion rate of the clinical pathway was 76.9%. There were five re-admissions (1.2%). The overall morbidity rate was 18% ( n = 72), and major complications (Clavien-Dindo IIIa or greater) occurred in 13 patients (3%). Complications were the causes for discharge variances in 68 cases (73%), while the attending surgeons' judgment was the cause in 25 cases (27%). On multivariate analysis, age (odds ratio = 2.23, 95% confidence interval = 1.38-3.60, p = 0.001) and operative time (odds ratio = 2.38, 95% confidence interval = 1.45-3.98, p = 0.001) were independent risk factors for discharge variances. A high completion rate of a clinical pathway with early oral intake and discharge setting for laparoscopic distal gastrectomy was achievable with an acceptably low re-admission rate. Laparoscopic distal gastrectomy is recommended as a first step for a clinical pathway with an early oral intake and discharge protocol.

Acquisition and maturation of oral microbiome throughout childhood: An update

PubMed Central

Sampaio-Maia, Benedita; Monteiro-Silva, Filipa

2014-01-01

Traditional microbiology concepts are being renewed since the development of new microbiological technologies, such as, sequencing and large-scale genome analysis. Since the entry into the new millennium, a lot of new information has emerged regarding the oral microbiome. This revision presents an overview of this renewed knowledge on oral microbial community acquisition in the newborn and on the evolution of this microbiome to adulthood. Throughout childhood, the oral microbial load increases, but the microbial diversity decreases. The initial colonizers are related to the type of delivery, personal relationships, and living environment. These first colonizers seem to condition the subsequent colonization, which will lead to more complex and stable ecosystems in adulthood. These early oral microbial communities, therefore, play a major role in the development of the adult oral microbiota and may represent a source of both pathogenic and protective microorganisms in a very early stage of human life. The implications of this knowledge on the daily clinical practice of odontopediatrics are highlighted. PMID:25097637

Oral cancer awareness and its determinants among a selected Malaysian population.

PubMed

Ghani, Wan Maria Nabillah; Doss, Jennifer Geraldine; Jamaluddin, Marhazlinda; Kamaruzaman, Dinan; Zain, Rosnah Binti

2013-01-01

To assess oral cancer awareness, its associated factors and related sources of information among a selected group of Malaysians. A cross-sectional survey was conducted on all Malaysian ethnic groups aged ≥15 years old at eight strategically chosen shopping malls within a two week time period. Data were analysed using chi-square tests and multiple logistic regression. Significance level was set at α<0.05. Most (84.2%) respondents had heard of oral cancer. Smoking was the most (92.4%) recognized high risk habit. Similar levels of awareness were seen for unhealed ulcers (57.3%) and red/white patches (58.0%) as signs of oral cancer. Age, gender, ethnicity, marital status, education, occupation and income were significantly associated with oral cancer awareness (p<0.05). There was a general lack of awareness regarding the risk habits, early signs and symptoms, and the benefits of detecting this disease at an early stage. Mass media and health campaigns were the main sources of information about oral cancer. In our Malaysian population, gender and age were significantly associated with the awareness of early signs and symptoms and prevention of oral cancer, respectively.

Diagnosis of Cognitive Impairment Compatible with Early Diagnosis of Alzheimer's Disease. A Bayesian Network Model based on the Analysis of Oral Definitions of Semantic Categories.

PubMed

Guerrero, J M; Martínez-Tomás, R; Rincón, M; Peraita, H

2016-01-01

Early detection of Alzheimer's disease (AD) has become one of the principal focuses of research in medicine, particularly when the disease is incipient or even prodromic, because treatments are more effective in these stages. Lexical-semantic-conceptual deficit (LSCD) in the oral definitions of semantic categories for basic objects is an important early indicator in the evaluation of the cognitive state of patients. The objective of this research is to define an economic procedure for cognitive impairment (CI) diagnosis, which may be associated with early stages of AD, by analysing cognitive alterations affecting declarative semantic memory. Because of its low cost, it could be used for routine clinical evaluations or screenings, leading to more expensive and selective tests that confirm or rule out the disease accurately. It should necessarily be an explanatory procedure, which would allow us to study the evolution of the disease in relation to CI, the irregularities in different semantic categories, and other neurodegenerative diseases. On the basis of these requirements, we hypothesise that Bayesian networks (BNs) are the most appropriate tool for this purpose. We have developed a BN for CI diagnosis in mild and moderate AD patients by analysing the oral production of semantic features. The BN causal model represents LSCD in certain semantic categories, both of living things (dog, pine, and apple) and non-living things (chair, car, and trousers), as symptoms of CI. The model structure, the qualitative part of the model, uses domain knowledge obtained from psychology experts and epidemiological studies. Further, the model parameters, the quantitative part of the model, are learnt automatically from epidemiological studies and Peraita and Grasso's linguistic corpus of oral definitions. This corpus was prepared with an incidental sampling and included the analysis of the oral linguistic production of 81 participants (42 cognitively healthy elderly people and 39

Investigation and identification of potential biomarkers in human saliva for the early diagnosis of oral squamous cell carcinoma.

PubMed

Wang, Qihui; Gao, Pan; Wang, Xiaoyi; Duan, Yixiang

2014-01-01

Oral cancer is 1 of the 6 most common human cancers, with an annual incidence of >300,000 cases worldwide. This study aimed to investigate potential biomarkers in human saliva to facilitate the early diagnosis of oral squamous cell carcinoma (OSCC). Unstimulated whole saliva obtained from OSCC patients (n=30) and apparently healthy individuals (n=30) were assayed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in hydrophilic interaction chromatography mode. The data were analyzed using a nonparametric Mann-Whitney U test, logistic regression, and the receiver operating characteristic (ROC) to evaluate the predictive power of each of 4 biomarkers, or combinations of biomarkers, for OSCC screening. Four potential salivary biomarkers demonstrated significant differences (P<0.05) in concentrations between patients at stages I-II and the healthy individuals. The area under the curve (AUC) values in control vs OSCC I-II mode based on choline, betaine, pipecolinic acid, and l-carnitine were 0.926, 0.759, 0.994, and 0.708, respectively. Four salivary biomarkers in combination yielded satisfactory accuracy (0.997), sensitivity (100%), and specificity (96.7%) in distinguishing OSCC I-II from control. Salivary metabolite biomarkers for the early diagnosis of OSCC were verified in this study. The proposed approach is expected to be applied as a potential technique of preclinical screening of OSCC. © 2013.

Effects of genistein on early-stage cutaneous wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

2011-07-08

Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

Folding of Polymer Chains in Early Stage of Crystallization

NASA Astrophysics Data System (ADS)

Yuan, Shichen; Miyoshi, Toshikazu

Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

Efficacy of oral health promotion in primary care practice during early childhood: creating positive changes in parent's oral health beliefs and behaviors.

PubMed

Mattheus, Deborah J

2014-06-01

Nurse practitioners frequently provide care to children suffering from poor oral health. Creative approaches to impacting dental disease are needed due to the current lack of traditional dental providers. This study investigated the effects of oral health promotion provided by primary care providers on parental oral health beliefs and behaviors. Participants receiving standard oral care during two well child visits and two additional enhanced oral health visits (n=44) were compared to participants receiving standard oral care during two well child visits alone (n=40). Results revealed changes in parent's perception of the importance of oral care for their children's primary teeth compared to general healthcare needs (p<0.05), response to brushing their children's teeth (p<0.0001), confidence in brushing their teeth (p<0.05) and frequency of brushing (p<0.0001) in both groups. This small but important study shows that oral health programs in primary care can produce changes that can improve oral health outcomes. Parents and children exposed to oral health programs during their frequent well child care visits in the first years of life may help decrease the rate of early childhood caries and improve their quality of life.

Radiation therapy in early-stage invasive breast cancer.

PubMed

Lin, Ray; Tripuraneni, Prabhakar

2011-06-01

The treatment of breast cancer involves a multi-disciplinary approach with radiation therapy playing a key role. Breast-conserving surgery has been an option for women with early-stage breast cancer for over two decades now. Multiple randomized trials now have demonstrated the efficacy of breast-conserving surgery followed by radiation therapy. With the advancements in breast imaging and the successful campaign for early detection of breast cancer, more women today are found to have early-stage small breast cancers. Patient factors (breast size, tumor location, history of prior radiation therapy, preexisting conditions such as collagen vascular disease, age, having prosthetically augmented breasts), pathological factors (margin status, tumor size, presence of extensive intraductal component requiring multiple surgical excisions), as well as patient preference are all taken into consideration prior to surgical management of breast cancer. Whole-breast fractionated radiation therapy between 5 and 7 weeks is considered as the standard of care treatment following breast-conserving surgery. However, new radiation treatment strategies have been developed in recent years to provide alternatives to the conventional 5-7 week whole-breast radiation therapy for some patients. Accelerated partial breast radiation therapy (APBI) was introduced because the frequency of breast recurrences outside of the surgical cavity has been shown to be low. This technique allows treatments to be delivered quicker (usually 1 week, twice daily) to a limited volume. Often times, this treatment involves the use of a brachytherapy applicator to be placed into the surgical cavity following breast-conserving surgery. Accelerated hypofractionated whole-breast irradiation may be another faster way to deliver radiation therapy following breast-conserving surgery. This journal article reviews the role of radiation therapy in women with early-stage breast cancer addressing patient selection in breast

Liquid biopsy for early stage lung cancer.

PubMed

Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

2018-04-01

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

Parental perceptions of children's oral health: The Early Childhood Oral Health Impact Scale (ECOHIS)

PubMed Central

Pahel, Bhavna Talekar; Rozier, R Gary; Slade, Gary D

2007-01-01

Background Dental disease and treatment experience can negatively affect the oral health related quality of life (OHRQL) of preschool aged children and their caregivers. Currently no valid and reliable instrument is available to measure these negative influences in very young children. The objective of this research was to develop the Early Childhood Oral Health Impact Scale (ECOHIS) to measure the OHRQL of preschool children and their families. Methods Twenty-two health professionals evaluated a pool of 45 items that assess the impact of oral health problems on 6-14-year-old children and their families. The health professionals identified 36 items as relevant to preschool children. Thirty parents rated the importance of these 36 items to preschool children; 13 (9 child and 4 family) items were considered important. The 13-item ECOHIS was administered to 295 parents of 5-year-old children to assess construct validity and internal consistency reliability (using Cronbach's alpha). Test-retest reliability was evaluated among another sample of parents (N = 46) using the intraclass correlation coefficient (ICC). Results ECOHIS scores on the child and parent sections indicating worse quality of life were significantly associated with fair or poor parental ratings of their child's general and oral health, and the presence of dental disease in the child. Cronbach's alphas for the child and family sections were 0.91 and 0.95 respectively, and the ICC for test-retest reliability was 0.84. Conclusion The ECOHIS performed well in assessing OHRQL among children and their families. Studies in other populations are needed to further establish the instrument's technical properties. PMID:17263880

Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment.

PubMed

van den Engel-Hoek, Lenie; Erasmus, Corrie E; Hendriks, Jan C M; Geurts, Alexander C H; Klein, Willemijn M; Pillen, Sigrid; Sie, Lilian T; de Swart, Bert J M; de Groot, Imelda J M

2013-05-01

Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based recommendations for safe swallowing. In this cross-sectional study, participants were divided into: early and late ambulatory stage (AS, n = 6), early non-ambulatory stage (ENAS, n = 7), and late non-ambulatory stage (LNAS, n = 11). Quantitative oral muscle ultrasound was performed to quantify echo intensity. Swallowing was assessed with a video fluoroscopic swallow study, surface electromyography (sEMG) of the submental muscle group and tongue pressure. Differences in outcome parameters among the three DMD stages were tested with analysis of variance. Oral muscles related to swallowing were progressively affected, starting in the AS with the geniohyoid muscle. Tongue (pseudo) hypertrophy was found in 70 % of patients in the ENAS and LNAS. Oral phase problems and post-swallow residue were observed, mostly in the LNAS with solid food. sEMG and tongue pressure data of swallowing solid food revealed the lowest sEMG amplitude, the longest duration and lowest tongue pressure in the LNAS. In case of swallowing problems in DMD, based on the disturbed mechanisms of swallowing, it is suggested to (1) adjust meals in terms of less solid food, and (2) drink water after meals to clear the oropharyngeal area.

[Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

PubMed

Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

2012-01-01

The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

Evaluation of an oral health education session for Early Head Start home visitors.

PubMed

Glatt, Kevin; Okunseri, Christopher; Flanagan, Diane; Simpson, Pippa; Cao, Yumei; Willis, Earnestine

2016-06-01

Home visiting programs promote the education and health of Early Head Start (EHS) children and pregnant women. However, EHS's oral health component is unevenly implemented. We conducted an educational intervention to improve oral health knowledge and motivational interviewing techniques among Wisconsin EHS home visitors. A questionnaire assessing oral health-related knowledge and confidence was administered to home visitors before and after an educational session. Changes between pre/post-responses were analyzed with McNemar's test and Wilcoxon Signed Rank test. After the intervention there were increases in both knowledge and confidence related to oral health communication. Knowledge increases were observed in such topics as fluoridation, dental caries, and caregivers' role in assisting and supervising children's tooth brushing. A brief educational intervention was associated with increased home visitor knowledge and confidence in communicating oral health messages to EHS caregivers and pregnant women. © 2016 American Association of Public Health Dentistry.

Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review.

PubMed

Nagi, R; Reddy-Kantharaj, Y-B; Rakesh, N; Janardhan-Reddy, S; Sahu, S

2016-07-01

Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct tool in early diagnosis of OSCC and OPMD.

Development of an early-stage toll revenue estimation model.

DOT National Transportation Integrated Search

2012-05-01

With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

Oral cancer: A multicenter study

PubMed Central

Rojanawatsirivej, Somsri; Thosaporn, Watcharaporn; Kintarak, Sompid; Subarnbhesaj, Ajiravudh; Darling, Mark; Kryshtalskyj, Eugene; Chiang, Chun-Pin; Shin, Hong-In; Choi, So-Young; Lee, Sang-shin; Shakib, Pouyan-Amini

2018-01-01

Background To determine the prevalence and clinicopathologic features of the oral cancer patients. Material and Methods Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Results Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as

Confidence interval estimation of the difference between two sensitivities to the early disease stage.

PubMed

Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

2014-03-01

Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

PubMed

Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

2014-10-01

The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

Signatures of unfolding in the early stages of protein denaturation

NASA Astrophysics Data System (ADS)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2012-04-01

A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

Safety, Pharmacokinetic, and Efficacy Studies of Oral DB868 in a First Stage Vervet Monkey Model of Human African Trypanosomiasis

PubMed Central

Thuita, John K.; Wolf, Kristina K.; Murilla, Grace A.; Liu, Qiang; Mutuku, James N.; Chen, Yao; Bridges, Arlene S.; Mdachi, Raymond E.; Ismail, Mohamed A.; Ching, Shelley; Boykin, David W.; Hall, James Edwin; Tidwell, Richard R.; Paine, Mary F.; Brun, Reto; Wang, Michael Zhuo

2013-01-01

There are no oral drugs for human African trypanosomiasis (HAT, sleeping sickness). A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization, thus reducing healthcare costs of HAT. The development of oral medications is a key objective of the Consortium for Parasitic Drug Development (CPDD). In this study, we investigated the safety, pharmacokinetics, and efficacy of a new orally administered CPDD diamidine prodrug, 2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868; CPD-007-10), in the vervet monkey model of first stage HAT. DB868 was well tolerated at a dose up to 30 mg/kg/day for 10 days, a cumulative dose of 300 mg/kg. Mean plasma levels of biomarkers indicative of liver injury (alanine aminotransferase, aspartate aminotransferase) were not significantly altered by drug administration. In addition, no kidney-mediated alterations in creatinine and urea concentrations were detected. Pharmacokinetic analysis of plasma confirmed that DB868 was orally available and was converted to the active compound DB829 in both uninfected and infected monkeys. Treatment of infected monkeys with DB868 began 7 days post-infection. In the infected monkeys, DB829 attained a median Cmax (dosing regimen) that was 12-fold (3 mg/kg/day for 7 days), 15-fold (10 mg/kg/day for 7 days), and 31-fold (20 mg/kg/day for 5 days) greater than the IC50 (14 nmol/L) against T. b. rhodesiense STIB900. DB868 cured all infected monkeys, even at the lowest dose tested. In conclusion, oral DB868 cured monkeys with first stage HAT at a cumulative dose 14-fold lower than the maximum tolerated dose and should be considered a lead preclinical candidate in efforts to develop a safe, short course (5–7 days), oral regimen for first stage HAT. PMID:23755309

Brief oral health promotion intervention among parents of young children to reduce early childhood dental decay.

PubMed

Arrow, Peter; Raheb, Joseph; Miller, Margaret

2013-03-20

Severe untreated dental decay affects a child's growth, body weight, quality of life as well as cognitive development, and the effects extend beyond the child to the family, the community and the health care system. Early health behavioural factors, including dietary practices and eating patterns, can play a major role in the initiation and development of oral diseases, particularly dental caries. The parent/caregiver, usually the mother, has a critical role in the adoption of protective health care behaviours and parental feeding practices strongly influence children's eating behaviours. This study will test if an early oral health promotion intervention through the use of brief motivational interviewing (MI) and anticipatory guidance (AG) approaches can reduce the incidence of early childhood dental decay and obesity. The study will be a randomised controlled study with parents and their new-born child/ren who are seen at 6-12 weeks of age by a child/community health nurse. Consenting parents will complete a questionnaire on oral health knowledge, behaviours, self-efficacy, oral health fatalism, parenting stress, prenatal and peri-natal health and socio-demographic factors at study commencement and at 12 and 36 months. Each child-parent pair will be allocated to an intervention or a standard care group, using a computer-generated random blocks. The standard group will be managed through the standard early oral health screening program; "lift the lip". The intervention group will be provided with tailored oral health counselling by oral health consultants trained in MI and AG.Participating children will be examined at 24, and 36 months for the occurrence of dental decay and have their height and weight recorded. Dietary information obtained from a food frequency chart will be used to determine food and dietary patterns. Data analysis will use intention to treat and per protocol analysis and will use tests of independent proportions and means. Multivariate

Brief oral health promotion intervention among parents of young children to reduce early childhood dental decay

PubMed Central

2013-01-01

Background Severe untreated dental decay affects a child’s growth, body weight, quality of life as well as cognitive development, and the effects extend beyond the child to the family, the community and the health care system. Early health behavioural factors, including dietary practices and eating patterns, can play a major role in the initiation and development of oral diseases, particularly dental caries. The parent/caregiver, usually the mother, has a critical role in the adoption of protective health care behaviours and parental feeding practices strongly influence children’s eating behaviours. This study will test if an early oral health promotion intervention through the use of brief motivational interviewing (MI) and anticipatory guidance (AG) approaches can reduce the incidence of early childhood dental decay and obesity. Methods The study will be a randomised controlled study with parents and their new-born child/ren who are seen at 6–12 weeks of age by a child/community health nurse. Consenting parents will complete a questionnaire on oral health knowledge, behaviours, self-efficacy, oral health fatalism, parenting stress, prenatal and peri-natal health and socio-demographic factors at study commencement and at 12 and 36 months. Each child–parent pair will be allocated to an intervention or a standard care group, using a computer-generated random blocks. The standard group will be managed through the standard early oral health screening program; “lift the lip”. The intervention group will be provided with tailored oral health counselling by oral health consultants trained in MI and AG. Participating children will be examined at 24, and 36 months for the occurrence of dental decay and have their height and weight recorded. Dietary information obtained from a food frequency chart will be used to determine food and dietary patterns. Data analysis will use intention to treat and per protocol analysis and will use tests of independent

The Influence of Student Characteristics on Early Elementary Oral Reading Fluency

ERIC Educational Resources Information Center

van Dijk, Wilhelmina

2018-01-01

Oral Reading Fluency (ORF) is a widely-used index of reading ability in early elementary grades; however, little information exists on predictive value of student characteristics on ORF scores (Wang, Algozzine, Ma, & Porfeli, 2011). A three-step sequential model was used to analyze the influence of student characteristics on scores (N = 2649)…

Occurrence of lymph node metastasis in early-stage parotid gland cancer.

PubMed

Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

2012-02-01

Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

Oral cancer: A multicenter study.

PubMed

Dhanuthai, K; Rojanawatsirivej, S; Thosaporn, W; Kintarak, S; Subarnbhesaj, A; Darling, M; Kryshtalskyj, E; Chiang, C-P; Shin, H-I; Choi, S-Y; Lee, S-S; Aminishakib, P

2018-01-01

To determine the prevalence and clinicopathologic features of the oral cancer patients. Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

PubMed

Jardim, J F; Francisco, A L N; Gondak, R; Damascena, A; Kowalski, L P

2015-01-01

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

Oral Cancer: Awareness and Knowledge Among Dental Patients in Riyadh.

PubMed

Al-Maweri, Sadeq Ali; Al-Soneidar, Walid Ahmed; Dhaifullah, Esam; Halboub, Esam Saleh; Tarakji, Bassel

2017-06-01

More than 50 % of oral cancer cases are diagnosed at advanced stages. Public knowledge about oral cancer can help in prevention and early detection of the disease. The aim of the present study was to assess the levels of awareness and knowledge about signs and risk factors of oral cancer among dental patients in Saudi Arabia. A self-administered questionnaire was used to collect information from 1410 randomly selected patients attending dental departments within public hospitals in Riyadh, Saudi Arabia. The collected data were analyzed using SPSS software. The significance level was set at P < 0.05. The study revealed that only 62.4 % were aware of oral cancer. Some 68.2 and 56.5 %, respectively, were able to correctly identify tobacco and alcohol as risk factors. More than two thirds of subjects had no knowledge about any signs of oral cancer. Participants with lower than university education were significantly less aware, and had much less knowledge, of the signs and risk factors of oral cancer. The knowledge regarding oral cancer among Saudi dental patients is alarmingly low. Interventions to improve public knowledge about oral cancer and attitudes towards early diagnosis and treatment are urgently indicated.

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential Impact of Close Surgical Margin on Local Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma.

PubMed

Jang, Jeon Yeob; Choi, Nayeon; Ko, Young-Hyeh; Chung, Man Ki; Son, Young-Ik; Baek, Chung-Hwan; Baek, Kwan-Hyuck; Jeong, Han-Sin

2017-06-01

The extent of surgical safety margin (gross tumor border to resection margin) in oral cancer surgery remains unclear, and no study has determined the differential impact of close surgical margin and microscopic extension according to primary tumor size in oral cancers. We retrospectively analyzed the clinical data of 325 patients with surgically treated oral cavity squamous cell carcinomas to determine the effect of a close surgical margin (<5 mm) (cSM 5 ) on local recurrence. In addition, the depth of microscopic tumor infiltration was determined in 90 available surgical specimens. The cSM 5 was not related to the risk of local tumor recurrence in early-stage oral cancer, while it significantly increased the rate of local tumor recurrence in resectable advanced-stage oral cancers (hazard ratio 3.157, 95 % confidence interval 1.050-9.407, p = 0.041). Addition of postoperative adjuvant radiation to early-stage tumors with cSM 5 did not further reduce the local recurrence rate compared to surgery alone. The depth of microscopic tumor extension from the gross tumor border was significantly associated with primary tumor thickness (ρ = 0.390, p < 0.001) and tumor sizes (ρ = 0.308, p = 0.003), which was a median (range) of 0.84 (0.14-2.32) mm in T1, 1.06 (0.20-4.34) mm in T2, and 1.77 (0.13-4.70) mm in T3-4. The cSM 5 was a significant risk factor for local recurrence only in advanced oral cancers, but not in early-stage tumors, where microscopic tumor extension was not beyond 3 mm in T1 tumors. Thus, the extent of surgical safety margin can be redefined according to the primary tumor size.

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

Background Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. Objectives To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. Search methods We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). Selection criteria We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Main results Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PubMed

Shimizu, Nobuyuki; Oki, Eiji; Tanizawa, Yutaka; Suzuki, Yutaka; Aikou, Susumu; Kunisaki, Chikara; Tsuchiya, Takashi; Fukushima, Ryoji; Doki, Yuichiro; Natsugoe, Shoji; Nishida, Yasunori; Morita, Masaru; Hirabayashi, Naoki; Hatao, Fumihiko; Takahashi, Ikuo; Choda, Yasuhiro; Iwasaki, Yoshiaki; Seto, Yasuyuki

2018-05-02

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

[An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

PubMed

Beliaev, A V

2000-01-01

A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

2010-08-01

To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

ERIC Educational Resources Information Center

Wöhrer, Veronika

2014-01-01

Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

Fertility sparing surgery in early stage epithelial ovarian cancer

PubMed Central

Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

2014-01-01

Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

The Relationship between Oral and Written Narratives: A Three-Year Longitudinal Study of Narrative Cohesion, Coherence, and Structure

ERIC Educational Resources Information Center

Pinto, Giuliana; Tarchi, Christian; Bigozzi, Lucia

2015-01-01

Background: The relationship between oral language and the writing process at early acquisition stages and the ways the former can enhance or limit the latter has not been researched extensively. Aims: The predictive relationship between kindergarten oral narrative competence and the first- and second-grade written narrative competence was…

Evaluation of the Early Childhood Oral Health Impact Scale in an Australian preschool child population.

PubMed

Arrow, P; Klobas, E

2015-09-01

Early childhood caries has significant impacts on children and their families. The Early Childhood Oral Health Impact Scale (ECOHIS) is an instrument for capturing the complex dimensions of preschool children's oral health. This study aimed to evaluate the reliability and validity of the instrument among Australian preschool children. Parents/children dyads (n = 286) participating in a treatment trial on early childhood caries completed the scale at baseline, and 33 parents repeated the questionnaire 2-3 weeks later. The validity and reliability of the ECOHIS was determined using tests for convergent and discriminant validity, internal reliability of the instrument and test-retest reliability. Scale impacts were strongly correlated with global oral health ratings (Spearman's correlations; r = 0.51, total score; r = 0.43, child impact; and r = 0.49, family impact; p < 0.001). The scale was significantly associated with children's caries experience, p < 0.001. Cronbach's alpha values were 0.87, 0.89 and 0.74 for the total, the child and the family domains, respectively. Test-retest reliability was 0.92, 0.89 and 0.78 for the total, child and family domains, respectively. The scale demonstrated acceptable validity and reliability for assessing the impact of early childhood caries among Australian preschool children. © 2015 Australian Dental Association.

[Treatment of non-small cell lung carcinoma in early stages].

PubMed

Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

2013-12-01

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Good daily habits during the early stages of life determine success throughout life.

PubMed

Kohyama, Jun

2016-01-01

This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

Nurses' experiences using a nursing information system: early stage of technology implementation.

PubMed

Lee, Ting-Ting

2007-01-01

Adoption of information technology in nursing practice has become a trend in healthcare. The impact of this technology on users has been widely studied, but little attention has been given to its influence at the beginning stage of implementation. Knowing the barriers to adopting technology could shorten this transition stage and minimize its negative influences. The purpose of this study was to explore nurses' experiences in the early stage of implementing a nursing information system. Focus groups were used to collect data at a medical center in Taiwan. The results showed that nurses had problems with the system's content design, had insufficient training, were concerned about data security, were stressed by added work, and experienced poor interdisciplinary cooperation. To smooth this beginning stage, the author recommends involving nurses early in the system design, providing sufficient training in keyboard entry skills, redesigning workflow, and improving interdisciplinary communication.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

PubMed

Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-03-01

Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

PubMed Central

Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-01-01

Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

Anorectal Manometric Dysfunctions in Newly Diagnosed, Early-Stage Parkinson's Disease

PubMed Central

Sung, Hye Young; Kim, Yeong-In; Lee, Kwang-Soo

2012-01-01

Background and Purpose Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. Methods We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. Results Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. Conclusions These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD. PMID:23091527

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

PubMed

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

PubMed Central

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

Characteristics of Early Stages of Corrosion Fatigue in Aircraft Skin

DOT National Transportation Integrated Search

1996-02-01

SRI International is conducting research to characterize and quantitatively describe the early stages of corrosion fatigue in the fuselage skin of commercial aircraft. Specific objectives are to gain an improved deterministic understanding of the tra...

Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Early infection risk with primary versus staged Hemodialysis Reliable Outflow (HeRO) graft implantation.

PubMed

Griffin, Andrew S; Gage, Shawn M; Lawson, Jeffrey H; Kim, Charles Y

2017-01-01

This study evaluated whether the use of a staged Hemodialysis Reliable Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs increased early infection risk compared with conventional primary HeRO implantation. A retrospective review was performed of 192 hemodialysis patients who underwent HeRO graft implantation: 105 patients underwent primary HeRO implantation in the operating room, and 87 underwent a staged implantation where a previously inserted tunneled central venous catheter was used for guidewire access for the venous outflow component. Within the staged implantation group, 32 were performed via an existing tunneled hemodialysis catheter (incidentally staged), and 55 were performed via a tunneled catheter inserted across a central venous occlusion in an interventional radiology suite specifically for HeRO implantation (intentionally staged). Early infection was defined as episodes of bacteremia or HeRO infection requiring resection ≤30 days of HeRO implantation. For staged HeRO implantations, the median interval between tunneled catheter insertion and conversion to a HeRO graft was 42 days. The overall HeRO-related infection rate ≤30 days of implantation was 8.6% for primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates of early bacteremia and HeRO resection requiring surgical resection were not significantly different between groups (P = .19 and P = .065, respectively), nor were age, gender, laterality, anastomosis to an existing arteriovenous access, human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass index, or graft location. None of the patient variables, techniques, or graft-related variables correlated significantly with the early infection rate. The staged HeRO implantation strategy did not result in an increased early infection risk compared with conventional primary implantation and is thus a reasonable strategy for HeRO insertion in hemodialysis patients

A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

ERIC Educational Resources Information Center

Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

2010-01-01

This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

Comparison of orofacial pain of patients with different stages of precancer and oral cancer.

PubMed

Yang, Yanjie; Zhang, Peipei; Li, Wenlu

2017-03-16

Orofacial pain impairs a patient's speech, swallowing, eating and interpersonal relations. Thirty-seven patients with a premalignant oral lesion, 124 patients with oral squamous cell carcinoma (OSSC), and 21 patients with a recurrence of OSSC were evaluated for their orofacial pain. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before they were prescribed analgesics for pain and before any treatment. Significant differences with respect to orofacial pain between the groups could be evaluatedwere observed. Patients with recurrence had the highest facial pain and patients with precancer had the lowest. Patients with OSSC and recurrence of OSSC reported significant levels of orofacial pain and functional restriction because of pain. Moreover, patients with recurrence of OSSC experienced significantly higher function-related pain, rather than pain qualities. These findings suggest that an important predictor for recurrence of OSSC may be the onset of orofacial pain that is exacerbated during function. The present study examined orofacial pain depending on the disease severity of precancer and oral cancer patients. Earlier recognition of symptoms of OSSC may improve early detection of its recurrence.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

PubMed

Gómez-Aristizábal, A; Sharma, A; Bakooshli, M A; Kapoor, M; Gilbert, P M; Viswanathan, S; Gandhi, R

2017-05-01

Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

PubMed

Davis, Rebecca L; Ohman, Jennifer M

2017-03-01

One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

Improved early outcome for end-stage dilated cardiomyopathy in children.

PubMed

McMahon, Anne-Marie; van Doorn, Carin; Burch, Michael; Whitmore, Pauline; Neligan, Sophie; Rees, Philip; Radley-Smith, Rosemary; Goldman, Allan; Brown, Katherine; Cohen, Gordon; Tsang, Victor; Elliott, Martin; de Leval, Marc R

2003-12-01

To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

Following iron speciation in the early stages of magnetite magnetosome biomineralization

DOE PAGES

Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

2016-02-26

Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe 3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structuremore » with a majority of iron present as Fe 3+ and trace amounts of Fe 2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

Challenges of Early Detection of Oral Cancer: Raising Awareness as a First Step to Successful Campaigning

ERIC Educational Resources Information Center

Baumann, Eva; Koller, Michael; Wiltfang, Jörg; Wenz, Hans-Jürgen; Möller, Björn; Hertrampf, Katrin

2016-01-01

In Germany, ~13 000 people are found to have oral and pharyngeal cancer every year. Awareness and knowledge about this cancer remain insufficient, particularly amongst elderly people. A campaign for early detection was launched in Northern Germany in April 2012. The first step of the campaign was to increase awareness about oral cancer. Prior to a…

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment | Division of Cancer Prevention

Cancer.gov

This randomized phase IIb trial studies how well ACTOplus met XR works in treating in patients with stage I-IV oral cavity or oropharynx cancer that are undergoing definitive treatment. Chemoprevention is the use of drugs to keep oral cavity or oropharynx cancer from forming or coming back. The use of ACTOplus met XR may slow disease progression in patients with oral cavity or

Early versus delayed oral fluids and food for reducing complications after major abdominal gynaecologic surgery.

PubMed

Charoenkwan, Kittipat; Matovinovic, Elizabeth

2014-12-12

This is an updated version of the original Cochrane review published in 2007. Traditionally, after major abdominal gynaecologic surgery postoperative oral intake is withheld until the return of bowel function. There has been concern that early oral intake would result in vomiting and severe paralytic ileus with subsequent aspiration pneumonia, wound dehiscence, and anastomotic leakage. However, evidence-based clinical studies suggest that there may be benefits from early postoperative oral intake. To assess the effects of early versus delayed (traditional) initiation of oral intake of food and fluids after major abdominal gynaecologic surgery. We searched the Menstrual Disorders and Subfertility Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), electronic databases (MEDLINE, EMBASE, CINAHL), and the citation lists of relevant publications. The most recent search was conducted 1 April 2014. We also searched a registry for ongoing trials (www.clinicaltrials.gov) on 13 May 2014. Randomised controlled trials (RCTs) were eligible that compared the effect of early versus delayed initiation of oral intake of food and fluids after major abdominal gynaecologic surgery. Early feeding was defined as oral intake of fluids or food within 24 hours post-surgery regardless of the return of bowel function. Delayed feeding was defined as oral intake after 24 hours post-surgery and only after signs of postoperative ileus resolution. Two review authors selected studies, assessed study quality and extracted the data. For dichotomous data, we calculated the risk ratio (RR) with a 95% confidence interval (CI). We examined continuous data using the mean difference (MD) and a 95% CI. We tested for heterogeneity between the results of different studies using a forest plot of the meta-analysis, the statistical tests of homogeneity of 2 x 2 tables and the I² value. We assessed the quality of the evidence using GRADE methods. Rates of developing

Early stages of figure-ground segregation during perception of the face-vase.

PubMed

Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

2011-04-01

The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

Metronomic chemotherapy in platinum-insensitive failures and/or early failures postmultimodality management in oral cancers

PubMed Central

Patil, Vijay M.; Noronha, Vanita; Joshi, Amit; Pinninti, Rakesh; Dhumal, Sachin; Bhattacharjee, Atanu; Prabhash, Kumar

2015-01-01

Purpose: Oral cancer patients with platinum-resistant disease and or early failures have limited treatment options. This analysis was planned to study the efficacy of metronomic chemotherapy in this group of patients. Materials and Methods: This was a retrospective analysis of oral cancer patients who had squamous cell carcinoma and had an early failure and/or platinum-insensitive failure. Early failure was defined as a failure either within 1-month of adjuvant radiotherapy or within 6 months of chemoradiation (CTRT). A sample size of 100 patients was selected for this study. If ≥39 of 100 patients would have survived at 6 months with metronomic chemotherapy, then additional studies would be warranted. Results: The ECOG PS was 0-1 in 92 patients and 2 in 8 patients. The subsite of primary was buccal mucosa in 38 patients (38%), anterior two-third tongue (oral tongue) in 51 patients (51%), and alveolus in 11 patients (11%). The median estimated overall survival was 110 days (95% confidence interval [CI]: 85-134 days). The proportion of patients surviving at 6 months was 26.4% (95% CI: 17.9-35.6). Conclusion: Metronomic combination of methotrexate and celecoxib failed to meet its prespecified efficacy limit and should not be used in these patients as routine. PMID:26855524

Can Intensity-Modulated Radiotherapy Preserve Oral Health-Related Quality of Life of Nasopharyngeal Carcinoma Patients?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pow, Edmond H.N., E-mail: ehnpow@hku.hk; Kwong, Dora L.W.; Sham, Jonathan S.T.

Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months aftermore » IMRT. Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.« less

Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

PubMed

Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

2018-04-23

Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

Oral health activities of early head start teachers directed toward children and parents.

PubMed

Kranz, Ashley M; Rozier, R Gary; Zeldin, Leslie P; Preisser, John S

2011-01-01

This cross-sectional study examined Early Head Start (EHS) teachers' oral health program activities and their association with teacher and program characteristics. Self-completed questionnaires were distributed to the staff in all EHS programs in North Carolina. Variables for dental health activities for parents (four items) and children (four items) were constructed as the sum of responses to a 0-4 Likert-type scale (never to very frequently). Ordinary least squares regression models examined the association between teachers' oral health program activities and modifiable teacher (oral health knowledge, values, self-efficacy, dental health training, perceived barriers to dental activities) and program (director and health coordinator knowledge and perceived barriers to dental activities) characteristics. Teachers in the parent (n=260) and child (n=231) analyses were a subset of the 485 staff respondents (98 percent response rate). Teachers engaged in child oral health activities (range = 0-16; mean = 9.0) more frequently than parent activities (range = 0-16; mean = 6.9). Teachers' oral health values, perceived oral health self-efficacy, dental training, and director and health coordinator knowledge were positively associated with oral health activities (P < 0.05). Perceived barriers were negatively associated with child activities (P < 0.05). The level of oral health activity in EHS programs is less than optimal. Several characteristics of EHS staff were identified that can be targeted with education interventions. Evidence for effectiveness of EHS interventions needs to be strengthened, but results of this survey provide encouraging findings about the potential effects of teacher training on their oral health practices.

Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

NASA Astrophysics Data System (ADS)

Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

2016-03-01

Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Chien-Yu; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

2010-11-15

Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-yearmore » overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.« less

Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

PubMed Central

Wu, Chia-Chou; Lin, Chih-Lung; Chen, Ting-Shou

2015-01-01

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID:26366411

Proteomics-based investigation of multiple stages of OSCC development indicates that the inhibition of Trx-1 delays oral malignant transformation.

PubMed

Chen, Xijuan; Hu, Qinchao; Wu, Tong; Wang, Chunyang; Xia, Juan; Yang, Linglan; Cheng, Bin; Chen, Xiaobing

2018-03-01

The majority of cases of oral squamous cell carcinoma (OSCC) develop from oral potentially malignant disorders, which have been confirmed to be involved in chronic oxidative stimulation. However, no effective treatment approaches have been used to prevent the development of dysplasia into cancerous lesions thus far. In the present study, a well-established OSCC model was used to detect proteomics profiles at different stages during oral malignant transformation. Of the 15 proteins that were found to be upregulated in both the dysplasia and carcinoma stages, the oxidative stress-associated proteins, thioredoxin-1 (Trx-1), glutaredoxin-1 and peroxiredoxin-2 were note as the proteins with significant changes in expression Trx-1 was identified to be the most significantly upregulated protein in the precancerous stage. Validation experiments confirmed that Trx-1 was overexpressed both in dysplasia and cancerous tissue samples, and the inhibition of Trx-1 was able to promote the apoptosis of OSCC cells under hypoxic conditions. Furthermore, the experimental application of a Trx-1-specific inhibitory agent in an animal model led to a lower cancerization rate and a delay in tumor formation. The possible mechanisms were associated with the increased apoptosis via a reactive oxygen species (ROS)-dependent pathway. Taken together, our findings indicate that Trx-1 may be an important target for delaying oral malignant transformation, which provides a novel therapeutic strategy for the prevention and treatment of OSCC.

Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma.

PubMed

Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

2016-05-26

Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P < 0.001). In addition, IL-37 expression was lower in OSCC with lymph node metastasis than those without metastasis (P < 0.01). What's more, overexpression of IL-37 in RAW264.7 cells remarkably reduced the pseudopodia, vacuolization and the expression of IL-6, TNF-α, and IL-1β. Finally, we found IL-37 and its receptor IL-18Rα but not its binding partner IL-18BP have similar tissue location and expression trend in different stages of oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.

Developmental rate and behavior of early life stages of bighead carp and silver carp

USGS Publications Warehouse

Chapman, Duane C.; George, Amy E.

2011-01-01

The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

Early-\\x90stage Electrical Breakdown involving Tunneling

NASA Astrophysics Data System (ADS)

Hjalmarson, Harold; Moore, Chris; Schultz, Peter; Bussman, Ezra; Scrymgeour, David; Hopkins, Matt

The early stage of electrical breakdown from a surface is assumed to involve field emission. In real-world applications, the electrical field is often assumed to be increased by geometrical effects. In addition to these enhancement effects, contamination by adsorbates can lead to reductions in the effective work functions. To develop a physics-based understanding beyond the use of these empirical effects, the field emission currents at early times are being computed and measured. The calculations involve a solution of the Boltzmann equation, and the measurements involve a scanning tunneling microscope. Early results from this collaborative theoretical-experimental project will be described in this presentation. The presentation will focus on results for an ideal system with an absence of geometrical effects. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia)

PubMed Central

Golombick, Terry; Diamond, Terrence H.; Manoharan, Arumugam; Ramakrishna, Rajeev

2016-01-01

Hypothesis. Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design. Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods. Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results. Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion. Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies. PMID:27154182

The Efficacy of Early Language Intervention in Mainstream School Settings: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Fricke, Silke; Burgoyne, Kelly; Bowyer-Crane, Claudine; Kyriacou, Maria; Zosimidou, Alexandra; Maxwell, Liam; Lervåg, Arne; Snowling, Margaret J.; Hulme, Charles

2017-01-01

Background: Oral language skills are a critical foundation for literacy and more generally for educational success. The current study shows that oral language skills can be improved by providing suitable additional help to children with language difficulties in the early stages of formal education. Methods: We conducted a randomized controlled…

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Early Stages of the Evolution of Life: a Cybernetic Approach

NASA Astrophysics Data System (ADS)

Melkikh, Alexey V.; Seleznev, Vladimir D.

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Early stages of the evolution of life: a cybernetic approach.

PubMed

Melkikh, Alexey V; Seleznev, Vladimir D

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

PubMed

Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F

2017-04-01

To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

PubMed

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T; Baumann, Heinz; Bellnier, David A; Sunar, Ulas; Tracy, Erin C; Rohrbach, Daniel J; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W

2013-12-01

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction. ©2013 AACR.

Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

PubMed Central

Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

2011-01-01

The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

PubMed

Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

2016-04-01

Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

PubMed

Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

2015-05-01

Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early-stage aeolian protodune development and migration

NASA Astrophysics Data System (ADS)

Nield, J. M.; Baddock, M. C.; Wiggs, G.

2017-12-01

Early-stage bedforms, or protodunes, can be observed to form on sandy beaches, desert gravels or superimposed on the surfaces of larger dunes and can develop topography of 0.1 m or more over several hours. These protodunes are the precursors to embryo and eventually mature dunes, and so it is important to understand how feedbacks between flow, transport and form contribute to this development sequence. Whilst theory and conceptual models have offered some explanation for protodune existence and development, we know surprisingly little about how these bedforms initiate and migrate because it is difficult to measure small changes in form (millimetres; seconds) on highly active surfaces of limited topographic expression. Here, we employ terrestrial laser scanning (TLS) to measure morphological change at the high frequency and spatial resolution (sub-millimetre) required to gain new insights into protodune behaviour. Along with TLS derived saltation and surface moisture, additional sediment flux and windspeed measurements help to elucidate how the protodune topography interacts with airflow and sand transport. We focus on a number of coastal bedforms in various development stages including a 0.06 m high protodune which grew vertically by 0.005 m in two hours with the switch from erosion to deposition identified to occur at a point 0.07 m upwind of the crest. This growth was associated with a reduction in time-averaged sediment flux of 18% over the crestal region. We also observed a decline in lower stoss slope steepness (by 3°) and a steepening of the lee slope, indicating a reshaping of initial protodune form towards the morphology of a more mature dune. Our findings highlight the crucial role of form-flow feedbacks, even on very small bedforms, in driving early-stage bedform growth and development, and show how the use of high resolution TLS to measure both surface topography and grains moving above the surface, can offer new insights into a long standing deficiency

Clinical implications of epigenetic regulation in oral cancer.

PubMed

D'Souza, Wendy; Saranath, Dhananjaya

2015-12-01

Oral cancer is a high incidence cancer which is of major public health concern in India being the most common cancer in males and fifth most common cancer in females in India, contributing to 26% of the global oral cancer burden. The major risk factors of oral cancer are tobacco, alcohol and high risk Human Papilloma Virus type 16/18. However, only 3-12% of the high risk individuals with dysplasia develop oral cancer. Thus, individual genomic variants representing the genomic constitution and epigenetic alterations play a critical role in the development of oral cancer. Extensive epigenetic studies on the molecular lesions including oncogenes, tumor suppressor genes, genes associated with apoptosis, DNA damage repair have been reported. The current review highlights epigenetic regulation with a focus on molecular biomarkers and epidrug therapy in oral cancer. Epigenetic regulation by hypermethylation, histone modifications and specific microRNAs are often associated with early events and advanced stages in oral cancer, and thus indicate epidrug therapy for intervention. The presence of epigenetic marks in oral lesions, cancers and tumor associated mucosa emphasizes indications as biomarkers and epidrugs with therapeutic potential for better patient management. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early childhood caries and infant oral health: Paediatricians’ and family physicians’ knowledge, practices and training

PubMed Central

Prakash, Preeti; Lawrence, Herenia P; Harvey, Bart J; McIsaac, Warren J; Limeback, Hardy; Leake, James L

2006-01-01

OBJECTIVES To assess the knowledge of early childhood caries and to examine the current preventive oral health-related practices and training among Canadian paediatricians and family physicians who provide primary care to children younger than three years. METHODS A cross-sectional, self-administered survey was mailed to a random sample of 1928 paediatricians and family physicians. RESULTS A total of 1044 physicians met the study eligibility criteria, and of those, 537 returned completed surveys, resulting in an overall response rate of 51.4% (237 paediatricians and 300 family physicians). Six questions assessed knowledge of early childhood caries; only 1.8% of paediatricians and 0.7% of family physicians answered all of these questions correctly. In total, 73.9% of paediatricians and 52.4% of family physicians reported visually inspecting children’s teeth; 60.4% and 44.6%, respectively, reported counselling parents or caregivers regarding teething and dental care; 53.2% and 25.6%, respectively, reported assessing children’s risk of developing tooth decay; and 17.9% and 22.3%, respectively, reported receiving no oral health training in medical school or residency. Respondents who felt confident and knowledgeable and who considered their role in promoting oral health as “very important” were significantly more likely to carry out oral health-related practices. CONCLUSION Although the majority of paediatricians and family physicians reported including aspects of oral health in children’s well visits, a reported lack of dental knowledge and training appeared to pose barriers, limiting these physicians from playing a more active role in promoting the oral health of children in their practices. PMID:19030271

Funding opportunities for investigators in the early stages of career development.

PubMed

Sumandea, C Amelia; Balke, C William

2009-03-10

Many sources of advice and guidance are available to the early career investigator. Generally, mentors serve as the primary source of information, although program and review officers are the most underutilized resources. This article organizes these opportunities to enable early career investigators to plot a rational trajectory for career success. A list of the major agencies that provide grant support for early career investigators is included. In addition, funding opportunities are organized on the basis of the stage in career development pathway and the type of terminal degree.

Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines.

PubMed

Kerawala, C; Roques, T; Jeannon, J-P; Bisase, B

2016-05-01

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessment and management of patients with cancer of the oral cavity and the lip. Recommendations • Surgery remains the mainstay of management for oral cavity tumours. (R) • Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R) • Elective neck treatment should be offered for all oral cavity tumours. (R) • Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control rates. (R) • Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R).

Flexibility in Early Stage Design of U. S. Navy Ships: An Analysis of Options

DTIC Science & Technology

2011-01-01

Flexibility in Early Stage Design of US Navy Ships: An Analysis of Options by Jonathan Page B.S., Systems Engineering, US Naval Academy, 2002...8217C/ v = (;!;!: ;: Pat Hale Director, Systems Design and Ma~ement Fellows Program E~i_yfering.S~~pivi~i~ Acceptedby...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Flexibility in Early Stage Design of U. S. Navy Ships: An

Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.

PubMed

Czajkowski, Krzysztof; Sienko, Jacek; Mogilinski, Mariusz; Bros, Magdalena; Szczecina, Roman; Czajkowska, Anna

2007-03-01

To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion. Randomized, parallel group, double-blind, double dummy-controlled study. Tertiary care university hospital. Fifty-three patients with threatened abortion and a living embryo. Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks, serial transvaginal Doppler ultrasound measurement of pulsatility index, resistance index, and systolic/diastolic ratio of the spiral arteries, the uterine arteries, and the intrachorionic area. Uteroplacental blood flow. The study demonstrated that vaginal progesterone administration, but not oral dydrogesterone treatment, results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio. Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at >9 weeks and was not associated with treatment regimen. Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio. Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion.

Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

PubMed

Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

2016-01-01

The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

PubMed

Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

2017-01-01

The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

Socioeconomic position and surgery for early-stage non-small-cell lung cancer: A population-based study in Denmark.

PubMed

Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne; Lidegaard Frederiksen, Birgitte; Jakobsen, Erik; Østerlind, Kell; Schüz, Joachim; Johansen, Christoffer; Oksbjerg Dalton, Susanne

2013-03-01

To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall and separately for stages I, II and IIIa. Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable income was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain the association with income or living alone for early-stage NSCLC patients. Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metamorphic density controls on early-stage subduction dynamics

NASA Astrophysics Data System (ADS)

Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

2013-04-01

Subduction is primarily driven by the densification of the downgoing oceanic slab, due to dynamic P-T-fields in subduction zones. It is crucial to unravel slab densification induced by metamorphic reactions to understand the influence on plate dynamics. By analyzing the density and metamorphic structure of subduction zones, we may gain knowledge about the driving, metamorphic processes in a subduction zone like the eclogitization (i.e., the transformation of a MORB to an eclogite), the breakdown of hydrous minerals and the release of fluid or the generation of partial melts. We have therefore developed a 2D subduction zone model down to 250 km that is based on thermodynamic equilibrium assemblage computations. Our model computes the "metamorphic density" of rocks as a function of pressure, temperature and chemical composition using the Theriak-Domino software package at different time stages. We have used this model to investigate how the hydration, dehydration, partial melting and fractionation processes of rocks all influence the metamorphic density and greatly depend on the temperature field within subduction systems. These processes are commonly neglected by other approaches (e.g., gravitational or thermomechanical in nature) reproducing the density distribution within this tectonic setting. The process of eclogitization is assumed as being important to subduction dynamics, based on the very high density (3.6 g/cm3) of eclogitic rocks. The eclogitization in a MORB-type crust is possible only if the rock reaches the garnet phase stability field. This process is primarily temperature driven. Our model demonstrates that the initiation of eclogitization of the slab is not the only significant process that makes the descending slab denser and is responsible for the slab pull force. Indeed, our results show that the densification of the downgoing lithospheric mantle (due to an increase of pressure) starts in the early subduction stage and makes a significant

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.

PubMed

Abdul-Razak, Muzib; Chung, Hsiang; Wong, Eva; Palme, Carsten; Veness, Michael; Farlow, David; Coleman, Hedley; Morgan, Gary

2017-01-01

Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting. We performed a prospective cohort study consisting of 30 consecutive patients with cT 1 - 2 N 0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III). A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template. SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions. © 2016 Royal Australasian College of Surgeons.

Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

ERIC Educational Resources Information Center

Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

2006-01-01

Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

Early Head Start, Pediatric Dental Use, and Oral Health–Related Quality of Life

PubMed Central

Burgette, J.M.; Preisser, J.S.; Weinberger, M.; King, R.S.; Rozier, R.G.

2017-01-01

The objective of the study was to examine the mediating effect of child dental use on the effectiveness of North Carolina Early Head Start (EHS) in improving oral health–related quality of life (OHRQoL). In total, 479 parents of children enrolled in EHS and 699 parents of Medicaid-matched children were interviewed at baseline when children were approximately 10 mo old and 24 mo later. In this quasi-experimental study, mediation analysis was performed using the counterfactual framework analysis, which employed 2 logit models with random effects: 1) for the mediator as a function of the treatment and covariates and 2) for the outcome as a function of the treatment, mediator, and covariates. The covariates were baseline dental OHRQoL, dental need, survey language, and a propensity score. We used in-person computer-assisted, structured interviews to collect information on demographic characteristics and dental use and to administer the Early Childhood Oral Health Impact Scale, a measure of OHRQoL. Dental use had a mediation effect in the undesired direction with a 2–percentage point increase in the probability of any negative impact to OHRQoL (95% confidence interval [CI], 0.3%–3.9%). Even with higher dental use by EHS participants, the probability of any negative impact to OHRQoL was approximately 8 percentage points lower if an individual were moved from the non-EHS group to the EHS group (95% CI, −13.9% to −1.2%). EHS increases child dental use, which worsens family OHRQoL. However, EHS is associated with improved OHRQoL overall. Knowledge Transfer Statement: Study results can inform policy makers that comprehensive early childhood education programs improve oral health–related quality of life (OHRQoL) for disadvantaged families with young children in pathways outside of clinical dental care. This awareness and its promotion can lead to greater resource investments in early childhood education programs. Information about the negative impacts of dental

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

NASA Astrophysics Data System (ADS)

Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

2015-01-01

One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

EPA Science Inventory

Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

ClinicalTrials.gov

2017-12-20

Human Papillomavirus Infection; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Oral health of early head start children: a qualitative study of staff, parents, and pregnant women.

PubMed

Mofidi, Mahyar; Zeldin, Leslie P; Rozier, R Gary

2009-02-01

We explored the oral health knowledge, attitudes, and activities of Early Head Start (EHS) staff members, parents, and pregnant women, along with their suggestions related to future oral health educational interventions targeting EHS children. Nine focus groups were conducted with EHS staff, parents, and pregnant women. Audiotapes of sessions were transcribed and entered into ATLAS.ti 5.0 for coding and analysis. Attitudes about the importance of children's oral health among parents and pregnant women were mixed. Staff members voiced responsibility for children's oral health but frustration in their inability to communicate effectively with parents. Parents in turn perceived staff criticism regarding how they cared for their children's oral health. Gaps were noted in the oral health activities of EHS programs. Participants expressed confusion regarding the application of Head Start oral health performance standards to EHS. The need for culturally sensitive, hands-on oral health education was highlighted. Tailored, theory-based interventions are needed to improve communication between EHS staff and families. Clear policies on the application of Head Start oral health performance standards to EHS are warranted. Educational activities should address the needs and suggestions of EHS participants.

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Correlation and comparative analysis of discriminative validity of the Scale of Oral Health Outcomes for Five-Year-Old Children (SOHO-5) and the Early Childhood Oral Health Impact Scale (ECOHIS) for dental caries.

PubMed

Fernandes, Izabella Barbosa; Ramos-Jorge, Joana; Ramos-Jorge, Maria Letícia; Bönecker, Marcelo; Abanto, Jenny; Marques, Leandro Silva; Paiva, Saul Martins

2015-03-10

The perceptions of parents and children regarding oral health are useful to oral public health and clinical practice in pediatric dentistry. The primary aim of the present study was to evaluate the correlation between the total and item scores of the Scale of Oral Health Outcomes for Five-Year-Old Children (SOHO-5) (parental version and child's self-reports) and the Early Childhood Oral Health Impact Scale (ECOHIS). Subsequently, the discriminative validity of these assessment tools regarding dental caries was compared. One hundred twenty-one children randomly selected in the city of Diamantina (Brazil) were submitted to oral examinations. Parents answered the ECOHIS and SOHO-5p (parental version) and children answered the SOHO-5c (child's self-reports). Statistical analysis involved the Mann-Whitney test as well as the calculation of Spearman's correlation coefficients. A significant correlation was found between the SOHO-5p and ECOHIS (r = 0.85), whereas no significant correlations were found between the SOHO-5c and SOHO-5p (r = 0.00) or between the SOHO-5c and ECOHIS (r = -0.41). Significant differences in the impact on quality of life were found between children with severe decay and no severe decay (caries free, with initial or established caries) both the ECOHIS and SOHO-5p (p ≤ 0.05), whereas no difference was found in SOHO-5c (p > 0.05). The ECOHIS and SOHO-5p were correlated with each other. The accounts of the children differed from their parents' reports and were not capable of discriminating dental caries in advanced stages of progression.

Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

2016-04-01

Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

PubMed

Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

2015-11-01

The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma

PubMed Central

Wikoff, William R.; Grapov, Dmitry; Fahrmann, Johannes F.; DeFelice, Brian; Rom, William; Pass, Harvey; Kim, Kyoungmi; Nguyen, UyenThao; Taylor, Sandra L.; Kelly, Karen; Fiehn, Oliver; Miyamoto, Suzanne

2015-01-01

Adenocarcinoma, a type of non-small-cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and non-malignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and non-malignant lung tissue pairs from current or former smokers with early stage (Stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared to non-malignant tissue. Cancer-associated biochemical alterations were characterized by: 1) decreased glucose levels, consistent with the Warburg effect, 2) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, 3) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, 4) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis and 5) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. PMID:25657018

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

[Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

PubMed

Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

2013-01-01

A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

PubMed Central

Kirk, David G.; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu

2012-01-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods. PMID:22544236

Involvement of Clostridium botulinum ATCC 3502 sigma factor K in early-stage sporulation.

PubMed

Kirk, David G; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia

2012-07-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σ(K) is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.

Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections.

PubMed

Li, Qigui; O'Neil, Michael; Xie, Lisa; Caridha, Diana; Zeng, Qiang; Zhang, Jing; Pybus, Brandon; Hickman, Mark; Melendez, Victor

2014-04-14

As anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malaria infections. The US Army is developing tafenoquine (TQ), an analogue of primaquine (PQ), which is expected to be more effective in preventing malaria in deployed military personnel. To compare the prophylactic efficacy of TQ and PQ, a transgenic Plasmodium berghei parasite expressing the bioluminescent reporter protein luciferase was utilized to visualize and quantify parasite development in C57BL/6 albino mice treated with PQ and TQ in single or multiple regimens using a real-time in vivo imaging system (IVIS). As an additional endpoint, blood stage parasitaemia was monitored by flow cytometry. Comparative pharmacokinetic (PK) and liver distribution studies of oral and intravenous PQ and TQ were also performed. Mice treated orally with three doses of TQ at 5 mg/kg three doses of PQ at 25 mg/kg demonstrated no bioluminescence liver signal and no blood stage parasitaemia was observed suggesting both drugs showed 100% causal activity at the doses tested. Single dose oral treatment with 5 mg TQ or 25 mg of PQ, however, yielded different results as only TQ treatment resulted in causal prophylaxis in P. berghei sporozoite-infected mice. TQ is highly effective for causal prophylaxis in mice at a minimal curative single oral dose of 5 mg/kg, which is a five-fold improvement in potency versus PQ. PK studies of the two drugs administered orally to mice showed that the absolute bioavailability of oral TQ was 3.5-fold higher than PQ, and the AUC of oral TQ was 94-fold higher than oral PQ. The elimination half-life of oral TQ in mice was 28 times longer than PQ, and the liver tissue distribution of TQ revealed an AUC that was 188-fold higher than PQ. The increased drug exposure levels and longer exposure time of oral TQ in the plasma and livers of mice highlight the lead quality attributes that explain the much improved efficacy of TQ when compared to PQ.

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

PubMed

Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

2017-05-01

Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

PubMed

Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

2017-06-01

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

Photodynamic Therapy with 3-(1’-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

PubMed Central

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T.; Baumann, Heinz; Bellnier, David A.; Sunar, Ulas; Tracy, Erin C.; Rohrbach, Daniel J.; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W.

2013-01-01

Purpose The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Results Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. Conclusion HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction. PMID:24088736

Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

PubMed

Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

2017-05-01

This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

ClinicalTrials.gov

2018-01-12

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Frustration Sculpts the Early Stages of Protein Folding.

PubMed

Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano

2015-09-07

The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Clinicopathological Study of Various Oral Cancer Diagnostic Techniques

PubMed Central

Ulaganathan, G.; Mohamed Niazi, K. Thanvir; Srinivasan, Soundarya; Balaji, V. R.; Manikandan, D.; Hameed, K. A. Shahul; Banumathi, A.

2017-01-01

Oral cancer is one of the most commonly occurring malignant tumors in the head and neck regions with high incident rate and mortality rate in the developed countries than in the developing countries. Generally, the survival rate of cancer patients may increase when diagnosed at early stage, followed by prompt treatment and therapy. Recently, cancer diagnosis and therapy design for a specific cancer patient have been performed with the advanced computer-aided techniques. The responses of the cancer therapy could be continuously monitored to ensure the effectiveness of the treatment process that hardly requires diagnostic result as quick as possible to improve the quality and patient care. This paper gives an overview of oral cancer occurrence, different types, and various diagnostic techniques. In addition, a brief introduction is given to various stages of immunoanalysis including tissue image preparation, whole slide imaging, and microscopic image analysis. PMID:29284926

Treatment of early-stage Hodgkin lymphoma.

PubMed

Engert, Andreas; Raemaekers, John

2016-07-01

Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

PubMed

Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

2018-05-01

Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

PubMed

Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

2018-01-01

Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

PubMed Central

Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

2015-01-01

Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

PubMed

Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

2015-01-01

Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

ClinicalTrials.gov

2016-04-19

Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

Loss of corticospinal tract integrity in early MS disease stages

PubMed Central

Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

2017-01-01

Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

Acute kidney injury is common with intravenous abuse of extended-release oral oxymorphone and delayed renal recovery rates are associated with increased KDIGO staging.

PubMed

Bonnecaze, Alex K; Wilson, Matthew Whitaker; Dharod, Ajay; Fletcher, Alison; Miller, P J

2017-08-12

Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100,000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, prevalence and outcomes of AKI among patients intravenously abusing extended-release oral oxymorphone were analyzed. A query of electronic medical records for "drug abuse" at an academic medical center during January 2012 to December 2015 was performed and yielded 2350 patients. Patients were further identified by documented intravenous abuse of extended-release oxymorphone. Patients were stratified based on multiple renal indices and outcomes. Potential confounders were also identified. 165 patients were found to have a documented history of intravenous abuse of extended-release oral oxymorphone. Prevalence of AKI in this population was a 47.8%. KDIGO stage-I patients consisted of 17.8% of patients with AKI, 40.5% were classified as KDIGO stage-II AKI, and 41.8% were classified as KDIGO stage-III AKI. Among patients with AKI, average age was found to be 37.5 years, 59.4% experienced renal recovery, 56.9% required intensive care unit admission, 13.9% progressed to end-stage renal disease (ESRD), and 7.6% expired during admission. Clinicians should be educated to help recognize intravenous abuse of extended-release oral oxymorphone and its associated effects. Our data suggests AKI is common in these patients; higher KDIGO staging appears to be associated with slower rates of renal recovery, increased comorbidities and progression to both CKD and ESRD. This article is protected by copyright. All rights reserved.

Perspectives of San Juan healthcare practitioners on the detection deficit in oral premalignant and early cancers in Puerto Rico: a qualitative research study

PubMed Central

2011-01-01

Background In Puerto Rico, relative to the United States, a disparity exists in detecting oral precancers and early cancers. To identify factors leading to the deficit in early detection, we obtained the perspectives of San Juan healthcare practitioners whose practice could be involved in the detection of such oral lesions. Methods Key informant (KI) interviews were conducted with ten clinicians practicing in or around San Juan, Puerto Rico. We then triangulated our KI interview findings with other data sources, including recent literature on oral cancer detection from various geographic areas, current curricula at the University of Puerto Rico Schools of Medicine and Dental Medicine, as well as local health insurance regulations. Results Key informant-identified factors that likely contribute to the detection deficit include: many practitioners are deficient in knowledge regarding oral cancer and precancer; oral cancer screening examinations are limited regarding which patients receive them and the elements included. In Puerto Rico, specialists generally perform oral biopsies, and patient referral can be delayed by various factors, including government-subsidized health insurance, often referred to as Reforma. Reforma-based issues include often inadequate clinician knowledge regarding Reforma requirements/provisions, diagnostic delays related to Reforma bureaucracy, and among primary physicians, a perceived financial disincentive in referring Reforma patients. Conclusions Addressing these issues may be useful in reducing the deficit in detecting oral precancers and early oral cancer in Puerto Rico. PMID:21612663

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Gender Differences in the Relationship between Oral Communicative Competence and Peer Rejection: An Explorative Study in Early Childhood Education

ERIC Educational Resources Information Center

van der Wilt, Femke; van Kruistum, Claudia; van der Veen, Chiel; van Oers, Bert

2016-01-01

This study investigated gender differences in the relationship between oral communicative competence and peer rejection in early childhood education. It was hypothesized that children with poorer oral communicative competence would be rejected by their peers more frequently and that the strength of this relationship would differ for boys and…

PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

PubMed

Brilhault, Jean; Noël, Vincent

2012-10-01

The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Exposure to coal combustion residues during metamorphosis elevates corticosterone content and adversely affects oral morphology, growth, and development in Rana sphenocephala

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, J.D.; Peterson, V.A.; Mendonca, M.T.

Coal combustion residues (CCRs) are documented to negatively impact oral morphology, growth, and development in larval amphibians. It is currently unclear what physiological mechanisms may mediate these effects. Corticosterone, a glucocorticoid hormone, is a likely mediator because when administered exogenously it, like CCRs, also negatively influences oral morphology, growth, and development in larval amphibians. In an attempt to identify if corticosterone mediates these effects, we raised larval Southern Leopard Frogs, Rana sphenocephala, on either sand or CCR substrate and documented effects of sediment type on whole body corticosterone, oral morphology, and time to and mass at key metamorphic stages. Coalmore » combustion residue treated tadpoles contained significantly more corticosterone than controls throughout metamorphosis. However, significantly more oral abnormalities occurred early in metamorphosis when differences in corticosterone levels between treatments were minimal. Overall, CCR-treated tadpoles took significantly more time to transition between key stages and gained less mass between stages than controls, but these differences between treatments decreased during later stages when corticosterone differences between treatments were greatest. Our results suggest endogenous increase in corticosterone content and its influence on oral morphology, growth and development is more complex than previously thought.« less

Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species

DTIC Science & Technology

2007-08-01

ERDC/TN ANSRP-07-2 August 2007 Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species by J...4. TITLE AND SUBTITLE Detection of Apoptosis in Early Life Stages as a Tool to Evaluate Chemical Control of Invasive Species 5a. CONTRACT NUMBER 5b...heralding apoptosis . Data analysis. An apoptotic index (API) was established by calculating the percentage of embryos in each life stage with

"A palliative end-stage COPD patient does not exist": a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD.

PubMed

Scheerens, Charlotte; Deliens, Luc; Van Belle, Simon; Joos, Guy; Pype, Peter; Chambaere, Kenneth

2018-06-20

Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD.

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

PubMed

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

PubMed Central

Maruyama, Tessho; Nishihara, Kazuhide; Umikawa, Masato; Arasaki, Akira; Nakasone, Toshiyuki; Nimura, Fumikazu; Matayoshi, Akira; Takei, Kimiko; Nakachi, Saori; Kariya, Ken-Ichi; Yoshimi, Naoki

2018-01-01

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2−ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=−0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

Factors associated with a positive willingness to practise oral health care in the future amongst oral healthcare and nursing students.

PubMed

Haresaku, S; Monji, M; Miyoshi, M; Kubota, K; Kuroki, M; Aoki, H; Yoshida, R; Machishima, K; Makino, M; Naito, T

2018-06-06

The purpose of this study was to identify the weak points in the knowledge and attitudes of first-year oral health care and nursing students towards oral health care and to identify the factors associated with their positive willingness to practise oral health care after becoming a health professional in order to develop oral healthcare curricula. The subjects were 88 first-year dental students (DSs), 64 dental hygiene students (DHSs) and 119 nursing students (NSs) enrolled in schools in Japan, as of April 2017. A questionnaire was distributed to subjects in each school to assess their knowledge and attitudes towards oral health care. Less than half knew that oral health care was also provided in cancer hospitals, hospices, acute care hospitals, maternity wards and psychiatric wards. Only 46.2% knew that oral health care was effective in the prevention of aspiration pneumonia. The level of knowledge and attitudes in NSs regarding oral health care were likely to be lowest amongst the student groups. Only NSs' high interest towards oral health care was associated with their positive willingness to practise oral health care in the future although oral health students' high perceptions and interest regarding oral health care were associated with the willingness. This study showed oral healthcare and nursing students' weak points regarding their attitudes and knowledge of oral health care at early stages. Oral health academic staff and professionals should develop effective oral healthcare curricula for oral healthcare students and help nursing staff develop a collaborative nursing oral healthcare curriculum to motivate nursing students. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Design of a smartphone-camera-based fluorescence imaging system for the detection of oral cancer

NASA Astrophysics Data System (ADS)

Uthoff, Ross

Shown is the design of the Smartphone Oral Cancer Detection System (SOCeeDS). The SOCeeDS attaches to a smartphone and utilizes its embedded imaging optics and sensors to capture images of the oral cavity to detect oral cancer. Violet illumination sources excite the oral tissues to induce fluorescence. Images are captured with the smartphone's onboard camera. Areas where the tissues of the oral cavity are darkened signify an absence of fluorescence signal, indicating breakdown in tissue structure brought by precancerous or cancerous conditions. With this data the patient can seek further testing and diagnosis as needed. Proliferation of this device will allow communities with limited access to healthcare professionals a tool to detect cancer in its early stages, increasing the likelihood of cancer reversal.

Distal Predominance of Electrodiagnostic Abnormalities in Early Stage Amyotrophic Lateral Sclerosis.

PubMed

Shayya, Luay; Babu, Suma; Pioro, Erik P; Li, Jianbo; Li, Yuebing

2018-05-09

We compare the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early stage amyotrophic lateral sclerosis (ALS). Single-site retrospective review Results: This study includes 122 consecutive patients with possible ALS as defined by revised El Escorial Criteria. Distal limb muscles show more frequent EMG abnormalities than proximal muscles. EDX yield is higher in the limb where weakness begins and when clinical signs of LMN dysfunction are evident. Adoption of Awaji criteria increases the yield of EMG positive segments significantly in the cervical (p<0.0005) and lumbosacral regions (P<0.0001), and upgrades 19 patients into probable and 1 patient into definite categories. Electromyographic abnormalities are distal limb-predominant in early stage ALS. A redefinition of an EDX-positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

PubMed

Schneider, Lon S

2014-03-01

The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Association Between Increased Vascular Density and Loss of Protective RAS in Early-Stage NPDR

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K . V.; Parsons-Wingerter, Patricia

2016-01-01

Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The prevailing paradigm of NPDR progression is that vessels drop out prior to abnormal, vision-impairing regrowth at late-stage proliferative diabetic retinopathy (DR). However, surprising results for our previous preliminary study 1 with NASA's VESsel GENeration Analysis (VESGEN) software showed that vessels proliferated considerably during moderate NPDR compared to drop out at both mild and severe NPDR. Validation of our hypothesis will support development of successful early-stage regenerative therapies such as vascular repair by circulating angiogenic cells (CACs). The renin-angiotensin system (RAS)is implicated in the pathogenesis of DR and in the function of CACs, a critical bone marrow-derived population that is instrumental in vascular repair.

Study of P21 Expression in Oral Lichen Planus and Oral Squamous Cell Carcinoma by Immunohistochemical Technique.

PubMed

Baghaei, Fahimeh; Shojaei, Setareh; Afshar-Moghaddam, Noushin; Zargaran, Massoumeh; Rastin, Verisheh; Nasr, Mohsen; Moghimbeigi, Abbas

2015-09-01

Lichen planus is a mucocutaneous disease that is relatively common in middle aged individuals. Some studies have shown that oral lichen planus has a potential to progress to squamous cell carcinoma.p21 is a cyclin-dependent kinase inhibitor that regulates the cell cycle, thus it acts as an inhibitor in cell proliferation. This study was aimed to evaluate and compare the immunostaining of p21 (as a proliferation inhibitory factor) in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). In this descriptive cross-sectional study, p21expression was investigated in 24 samples of oral lichen planus (OLP), 24 samples of oral squamous cell carcinoma (OSCC) and 24 samples of oral epithelial hyperplasia (OEH) by employing immunohistochemical staining. The mean percentage of p21-positive cells in OSCC (54.5±6.6) was significantly higher than that in OLP (32.8±6.08) and OEH (9.4±3.8). Moreover, OLP samples expressed p21 significantly higher than the OEH. Kruskal Wallis test revealed a statistically significant difference between the groups regarding the intensity of staining (p< 0.001). According to the findings of this study, the expression of p21 might be related to the potential carcinogenic transformation of lichen planus to SCC. Therefore, continuous follow-up periods for OLP are recommended for diagnosis of the malignant transformations in early stages.

Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis.

PubMed

Singh, Abhayjeet; Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

2015-10-01

Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients.

Gender- and ethnicity-specific survival trends of oral cavity and oropharyngeal cancers in British Columbia.

PubMed

Auluck, Ajit; Hislop, Greg; Bajdik, Chris; Hay, John; Bottorff, Joan L; Zhang, Lewei; Rosin, Miriam P

2012-12-01

A shift in etiology of oral cancers has been associated with a rise in incidence for oropharyngeal cancers (OPC) and decrease for oral cavity cancers (OCC); however, there is limited information about population-based survival trends. We report epidemiological transitions in survival for both OPC and OCC from a population-based cancer registry, focusing upon gender and ethnic differences. All primary oral cancers diagnosed between 1980 and 2005 were identified from the British Columbia Cancer Registry and regrouped into OPC and OCC by topographical subsites, time periods (1980-1993 and 1994-2005), stage at diagnosis, and ethnicity. Cases were then followed up to December 2009. Using gender-based analysis, actuarial life tables were used to calculate survival rates, which were compared using Kaplan-Meier curves and log-rank tests. For OPC, survival improved, significant for tonsil and base of tongue in men and marginally significant at base of tongue in women. This improvement occurred in spite of an increase in late-stage diagnosis for OPC in both genders. Interestingly, there was no difference in survival for early- and late-stage disease for OPC in men. For OCC, there was a decrease in survival for floor of mouth cancers in both genders although significant in women only. South Asians had the poorest survival for OCC in both genders. Survival for OPC improved, more dramatically in men than women, in spite of late-stage diagnosis and increasing nodal involvement. Given the poor survival rates and need for early detection, targeted OCC screening programs are required for South Asians.

Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections

PubMed Central

2014-01-01

Background As anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malaria infections. The US Army is developing tafenoquine (TQ), an analogue of primaquine (PQ), which is expected to be more effective in preventing malaria in deployed military personnel. Methods To compare the prophylactic efficacy of TQ and PQ, a transgenic Plasmodium berghei parasite expressing the bioluminescent reporter protein luciferase was utilized to visualize and quantify parasite development in C57BL/6 albino mice treated with PQ and TQ in single or multiple regimens using a real-time in vivo imaging system (IVIS). As an additional endpoint, blood stage parasitaemia was monitored by flow cytometry. Comparative pharmacokinetic (PK) and liver distribution studies of oral and intravenous PQ and TQ were also performed. Results Mice treated orally with three doses of TQ at 5 mg/kg three doses of PQ at 25 mg/kg demonstrated no bioluminescence liver signal and no blood stage parasitaemia was observed suggesting both drugs showed 100% causal activity at the doses tested. Single dose oral treatment with 5 mg TQ or 25 mg of PQ, however, yielded different results as only TQ treatment resulted in causal prophylaxis in P. berghei sporozoite-infected mice. TQ is highly effective for causal prophylaxis in mice at a minimal curative single oral dose of 5 mg/kg, which is a five-fold improvement in potency versus PQ. PK studies of the two drugs administered orally to mice showed that the absolute bioavailability of oral TQ was 3.5-fold higher than PQ, and the AUC of oral TQ was 94-fold higher than oral PQ. The elimination half-life of oral TQ in mice was 28 times longer than PQ, and the liver tissue distribution of TQ revealed an AUC that was 188-fold higher than PQ. Conclusions The increased drug exposure levels and longer exposure time of oral TQ in the plasma and livers of mice highlight the lead quality attributes that explain the much

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

PubMed

Zhao, Jingxin; Zhai, Fei; Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

PubMed Central

Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

PubMed

Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

2012-12-01

Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel intravital multi-harmonic generation microscope for early diagnosis of oral cancer

NASA Astrophysics Data System (ADS)

Cheng, Yu-Hsiang; Lin, Chih-Feng; Shih, Ting-Fang; Sun, Chi-Kuang

2013-03-01

Oral cancer is one of the most frequently diagnosed human cancers and leading causes of cancer death all over the world, but the prognosis and overall survival rate are still poor because of delay in diagnosis and lack of early intervention. The failure of early diagnosis is due to insufficiency of proper diagnostic and screening tools and most patients are reluctant to undergo biopsy. Optical virtual biopsy techniques, for imaging cells and tissues at microscopic details capable of differentiating benign from malignant lesions non-invasively, are thus highly desirable. A novel multi-harmonic generation microscope, excited by a 1260 nm Cr:forsterite laser, with second and third harmonic signals demonstrating collagen fiber distribution and cell morphology in a sub-micron resolution, was developed for clinical use. To achieve invivo observation inside the human oral cavity, a small objective probe with a suction capability was carefully designed for patients' comfort and stability. By remotely changing its focus point, the same objective can image the mucosa surface with a low magnification, illuminated by side light-emitting diodes, with a charge-coupled device (CCD) for site location selection before the harmonic generation biopsy was applied. Furthermore, the slow galvanometer mirror and the fast resonant mirror provide a 30 fps frame rate for high-speed real-time observation and the z-motor of this system is triggered at the same rate to provide fast 3D scanning, again ensuring patients' comfort. Focusing on the special cytological and morphological changes of the oral epithelial cells, our preliminary result disclosed excellent consistency with traditional histopathology studies.

Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

PubMed

Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

2017-01-01

Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

2005-01-01

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development

PubMed Central

Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

2014-01-01

The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

[Early childhood caries--a public oral health problem].

PubMed

Dănilă, I; Evghenikos, Adina

2007-01-01

The purpose of this study was to determine the prevalence and severity of dental caries in preschool children from nurseries and kindergartens in Iaşi, an urban city in Romania. The study assessed the dental health status in 2 age groups. The first group included 366 children aged 2, 5-3 years and the second group included 455 children aged 4,5-5 years in 2005. The children were subjected to dental examination in 2005 and 2006 and the prevalence and severity of caries for each age group were determined. Evaluation was based on questionnaire completed by mothers and on clinical assessment of preschool children's oral health status. The mean number of decayed, missing and filled primary teeth (dmft) in the first group was 1.76 in 2005 and 2.39 in 2006, while the significant caries index increased from 4.79 to 6.35 during this period of time. For the 4.5-5 year children, the mean values for the dmft index were 3.95 in 2005 and 3.67 in 2006, while significant caries index increased from 7.89 to 8.4. Early childhood caries are the result of both inadequate diet behavior and cariogenic germs transmission from mother. The presence and extension of carious lesions in primary teeth are the most important predictors of permanent teeth disease. The high prevalence and severity of dental caries in pre-school children indicated that dental health program that include both prevention and treatment services targeted for young children and their parents is urgently needed. Socio-economic status improvement, changes in lifestyle, effective use of oral health services, and most of all, oral hygiene and use of fluoride would lead to obvious changes in caries prevalence and severity of disease. The study high-lights the importance of change of attitudes and improvement of knowledge in parents, children and educators in order to reach a healthy lifestyle.

Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer

ClinicalTrials.gov

2013-01-24

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

PubMed

Kurzer, Jason H; Weinberg, Olga K

2018-05-25

Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

PubMed

Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

The Value of Sentinel Lymph Node Biopsy in Oral Cavity Cancers

PubMed Central

Kaya, İsa; Göde, Sercan; Öztürk, Kerem; Turhal, Göksel; Aliyev, Araz; Akyıldız, Serdar; Duygun, Ülkem Yararbaş; Uluöz, Ümit; Yavuzer, Atilla

2015-01-01

Objective The aim of this study was to establish the effectiveness of sentinel lymph node biopsy in the detection of metastasis in N0 necks of T1–T2 early-stage oral cavity cancers. Materials and Methods Twenty neck dissections were performed in 18 patients diagnosed with T1 and T2 oral cavity cancer, with an indication for elective neck dissection between November 2007 and January 2011. The male to female ratio was 12:8, with a mean age of 54.5 years (range 28–76). Eight of the dissections were performed for lower lip cancer, 7 for tongue cancer, and 5 for floor of the mouth cancer. Sentinel lymph node biopsy was used to detect metastatic lymph nodes. Tc99m radionuclide injection was administered to the periphery of the tumor 24 h before the operation, and a lymphoscintigraphy image was obtained 30 min after the injection. Sentinel lymph nodes were localized and excised on the day of surgery using static lymphoscintigraphy images and a gamma probe. Sentinel lymph nodes were sent for a frozen section examination, and either a selective or a comprehensive neck dissection was performed for each neck according to the results. Results After the final histopathological examination of the specimens, the negative predictive value, the positive predictive value, the accuracy of the sentinel lymph node biopsy, and frozen section accuracy were found to be 100%. Conclusion Sentinel lymph node biopsy was found to be an efficient method in the pathological staging and management of the N0 neck in early T-stage oral cavity cancers. PMID:29391982

Transoral Robotic Surgery in Treating Patients With Benign or Stage I-IV Head and Neck Cancer

ClinicalTrials.gov

2014-11-07

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage

Probiotics and oral health: an update.

PubMed

Pradeep, K; Kuttappa, M A; Prasana, K R

2014-02-01

Probiotics are micro-organisms, principally bacteria, which, when ingested, confer health benefits beyond basic nutrition. Probiotics have been extensively studied for their health promoting effects. The main feld of research has been focussed on the gastro-intestinal tract. However, in the past few years probiotics have also been investigated from an oral health perspective and their use has shown promising results with respect to control of chronic conditions, such as dental caries, periodontitis, halitosis and candidial infections. Despite the immense potential of probiotics, hardly any randomised, controlled trials have been conducted on their action and application and studies on their effects on oral health are still in early stages. Hence, more research is needed before any evidence-based conclusions can be drawn. This paper considers some recent literature and insights on which further investigations could be based.

Contemporary Diagnostic Imaging of Oral Squamous Cell Carcinoma – A Review of Literature

PubMed Central

Pałasz, Paulina; Adamski, Łukasz; Górska-Chrząstek, Magdalena; Starzyńska, Anna; Studniarek, Michał

2017-01-01

Summary Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity and constitutes 95% of all cancers of this area. Men are affected twice as commonly as women, primarily if they are over 50 years of age. Forty percent of the lesions are localized in the tongue and 30% in the floor of the oral cavity. OSCC often affects upper and lower gingiva, buccal mucous membrane, the retromolar triangle and the palate. The prognosis is poor and the five-year survival rate ranges from 20% (OSCC in the floor of the mouth) to 60% (OSCC in the alveolar part of the mandible). Treatment is difficult, because of the localization and the invasiveness of the available methods. The diagnosis is made based on a histopathological examination of a biopsy sample. The low detection rate of early oral SCC is a considerable clinical issue. Although the oral cavity can be easily examined, in the majority of cases oral SCC is diagnosed in its late stages. It is difficult to diagnose metastases in local lymph nodes and distant organs, which is important for planning the scope of resection and further treatment, graft implantation, and differentiation between reactive and metastatic lymph nodes as well as between disease recurrence and scars or adverse reactions after surgery or radiation therapy. Imaging studies are performed as part of the routine work-up in oral SCC. However, it is difficult to interpret the results at the early stages of the disease. The following imaging methods are used – dental radiographs, panoramic radiographs, magnetic resonance imaging with diffusion-weighted and dynamic sequences, perfusion computed tomography, cone beam computed tomography, single-photon emission computed tomography, hybrid methods (PET/CT, PET/MRI, SPECT/CT) and ultrasound. Some important clinical problems can be resolved with the use of novel modalities such as MRI with ADC sequences and PET. The aim of this article is to describe oral squamous cell carcinoma as it appears in

The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

PubMed

Fleming, Jonathan J

2015-02-01

A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. Project HOPE—The People-to-People Health Foundation, Inc.

In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.

PubMed

Hellbach, Katharina; Yaroshenko, Andre; Meinel, Felix G; Yildirim, Ali Ö; Conlon, Thomas M; Bech, Martin; Mueller, Mark; Velroyen, Astrid; Notohamiprodjo, Mike; Bamberg, Fabian; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

2015-07-01

The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher

Pyrosequencing analysis of oral microbiota in children with severe early childhood dental caries.

PubMed

Jiang, Wen; Zhang, Jie; Chen, Hui

2013-11-01

Severe early childhood caries are a prevalent public health problem among preschool children throughout the world. However, little is known about the microbiota found in association with severe early childhood caries. Our study aimed to explore the bacterial microbiota of dental plaques to study the etiology of severe early childhood caries through pyrosequencing analysis based on 16S rRNA gene V1-V3 hypervariable regions. Forty participants were enrolled in the study, and we obtained twenty samples of supragingival plaque from caries-free subjects and twenty samples from subjects with severe early childhood caries. A total of 175,918 reads met the quality control standards, and the bacteria found belonged to fourteen phyla and sixty-three genera. Our results show the overall structure and microbial composition of oral bacterial communities, and they suggest that these bacteria may present a core microbiome in the dental plaque microbiota. Three genera, Streptococcus, Granulicatella, and Actinomyces, were increased significantly in children with severe dental cavities. These data may facilitate improvements in the prevention and treatment of severe early childhood caries.

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

PubMed

Omidvari, K; de Boisblanc, B P; Karam, G; Nelson, S; Haponik, E; Summer, W

1998-08-01

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

Dyslipidogenic microangiopathy in guinea pigs at early stages of atherogenesis.

PubMed

Bersenev, A V; Klimenko, E D; Kobozeva, L P; Michunskaya, A B; Onishchenko, N A; Pozdnyakov, O M

2003-08-01

We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.

Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

PubMed Central

Butler, Pamela D.; Zemon, Vance; Schechter, Isaac; Saperstein, Alice M.; Hoptman, Matthew J.; Lim, Kelvin O.; Revheim, Nadine; Silipo, Gail; Javitt, Daniel C.

2005-01-01

Background Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-d-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. Objectives To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. Design, Setting, and Participants Between-group study at an inpatient state psychiatric hospital and out-patient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. Main Outcome Measures (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. Results Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P=.001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P=.001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P=.002), which was in turn related to deficits in complex visual processing (P≤.04). Both

Fish early life stage: Developing AOPs to support targeted reduction and replacement

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

Chemotherapy of Second Stage Human African Trypanosomiasis: Comparison between the Parenteral Diamidine DB829 and Its Oral Prodrug DB868 in Vervet Monkeys

PubMed Central

Thuita, John K.; Wolf, Kristina K.; Murilla, Grace A.; Bridges, Arlene S.; Boykin, David W.; Mutuku, James N.; Liu, Qiang; Jones, Susan K.; Gem, Charles O.; Ching, Shelley; Tidwell, Richard R.; Wang, Michael Z.; Paine, Mary F.; Brun, Reto

2015-01-01

Human African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868) were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5). Oral DB868 was less successful, with no cures (0/2) at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatment for second stage HAT. PMID:25654243

Morphometric discrimination of early life stage Lampetra tridentata and L richardsoni (Petromyzonidae) from the Columbia river basin

USGS Publications Warehouse

Meeuwig, M.H.; Bayer, J.M.; Reiche, R.A.

2006-01-01

The effectiveness of morphometric and meristic characteristics for taxonomic discrimination of Lampetra tridentata and L. richardsoni (Petromyzonidae) during embryological, prolarval, and early larval stages (i.e., age class 1) were examined. Mean chorion diameter increased with time from fertilization to hatch and was significantly greater for L. tridentata than for L. richardsoni at 1, 8, and 15 days postfertilization. Lampetra tridentata larvae had significantly more trunk myomeres than L. richardsoni; however, trunk myomere numbers were highly variable within species and deviated from previously published data. Multivariate examinations of prolarval and larval L. tridentata (7.2-11.0 mm; standard length) and L. richardsoni (6.6-10.8 mm) were conducted based on standard length and truss element lengths established from eight homologous landmarks. Principal components analysis indicated allometric relationships among the morphometric characteristics examined. Changes in body shape were indicated by groupings of morphometric characteristics associated with body regions (e.g., oral hood, branchial region, trunk region, and tail region). Discriminant function analysis using morphometric characteristics was successful in classifying a large proportion (>94.7%) of the lampreys sampled. 

Developing Leadership for Early Childhood Professionals through Oral Inquiry: Strengthening Equity through Making Particulars Visible in Dilemmas of Practice

ERIC Educational Resources Information Center

Nicholson, Julie Marie; Kroll, Linda

2015-01-01

Developing leadership among early childhood professionals has become increasingly important as investing in children's early years has been championed as a public and private national and international priority. Two case studies present how oral inquiry and specifically, the Prospect Center's Descriptive Review of a Professional Dilemma of…

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens

PubMed Central

2018-01-01

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age. PMID:29185274

Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

PubMed

Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

2016-04-22

Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

PubMed

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

PubMed Central

Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

2014-01-01

Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

Reading skills in young adolescents with a history of Specific Language Impairment: The role of early semantic capacity.

PubMed

Buil-Legaz, Lucía; Aguilar-Mediavilla, Eva; Rodríguez-Ferreiro, Javier

2015-01-01

This study assessed the reading skills of 19 Spanish-Catalan children with Specific Language Impairment (SLI) and 16 age-matched control children. Children with SLI have difficulties with oral language comprehension, which may affect later reading acquisition. We conducted a longitudinal study examining reading acquisition in these children between 8 and 12 years old and we relate this data with early oral language acquisition at 6 years old. Compared to the control group, the SLI group presented impaired decoding and comprehension skills at age 8, as evidenced by poor scores in all the assessed tasks. Nevertheless, only text comprehension abilities appeared to be impaired at age 12. Individual analyses confirmed the presence of comprehension deficits in most of the SLI children. Furthermore, early semantic verbal fluency at age 6 appeared to significantly predict the reading comprehension capacity of SLI participants at age 12. Our results emphasize the importance of semantic capacity at early stages of oral language development over the consolidation of reading acquisition at later stages. Readers will recognize the relevance of prior oral language impairment, especially semantic capacity, in children with a history of SLI as a risk factor for the development of later reading difficulties. Copyright © 2015 Elsevier Inc. All rights reserved.

Is it time to incorporate 'depth of infiltration' in the T staging of oral tongue and floor of mouth cancer?

PubMed

Piazza, Cesare; Montalto, Nausica; Paderno, Alberto; Taglietti, Valentina; Nicolai, Piero

2014-04-01

To summarize recent acquisitions in three-dimensional tongue and floor of mouth anatomy that can help in better evaluation of the pathways of cancer progression within these oral subsites, thus giving some hints for refining of the current TNM staging system. The Visual Human Project is an initiative aimed at establishing a three-dimensional dataset of anatomy of two cadavers made available free to the scientific community. Visual human data have been analyzed by specific software thus improving our three-dimensional understanding of the tongue myostructure. It is already known that there is limited prognostic utility in using the two-dimensional surface diameter alone as criterion for T1-T3 definition. Recently, also the T4a categorization for the infiltration of 'deep' or extrinsic tongue muscles has been criticized. This is largely because the descriptor 'deep' does not take into account the fact that considerable portions of these muscles lie in a very superficial plane. Different prognosticators have been proposed for inclusion into the TNM staging system of oral cancer but 'depth of tumor infiltration' seems to be the most robust, universally recognized, and reproducible in the preoperative, intraoperative, and postoperative settings. Oral tongue and floor of mouth cancer needs to be classified according to a revised TNM staging system in which 'depth of infiltration' should be taken into account. An 'ideal cut off' for distinguishing 'low' (T1-T2) from 'high-risk' (T3-T4) categories has been proposed based on the literature review, but needs retrospective as well as large prospective trials before its validation.

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Two consecutive pregnancies in early and late stage of amyotrophic lateral sclerosis.

PubMed

Sarafov, Stayko; Doitchinova, Maryana; Karagiozova, Zhvka; Slancheva, Boriana; Dengler, Reinhard; Petri, Susanne; Kollewe, Katja

2009-01-01

There are few reports on pregnancies in sporadic and familial amyotrophic lateral sclerosis (ALS). We report on a young woman with sporadic ALS who gave birth twice during the course of her disease. The first pregnancy occurred 13 months after the onset of symptoms, and one month after diagnosis. The pregnancy was uncomplicated and resulted in vaginal delivery of a healthy boy. Fifteen months later, when she was already bed-ridden, she became pregnant again. She received a percutaneous endoscopic gastrostomy in the 21st gestational week and underwent early Caesarean section in the 34th week of gestation. The child was ventilated for 72 h in a neonatological unit. The patient was tracheotomized and ventilated two months later, i.e. 47 months after symptom onset, and died nine months later from gastrointestinal haemorrhage. Her two children have developed without abnormalities to date. This case confirms that pregnancies in early-stage ALS can develop normally and may result in uncomplicated vaginal delivery. Pregnancies in late stages may be critical for mother and child, and early delivery by Caesarean section may become necessary although neonatal outcome can be good.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis

PubMed Central

Irani, Soussan

2016-01-01

Many types of cancers develop in the oral and maxillofacial region. Squamous cell carcinoma is the most common cancer and constitutes over 90 percent of these tumors. Malignant transformation is a genetic process, which later makes a phenotyping change at the cellular level. Some cancers such as oral squamous cell carcinomas (OSCCs) develop from pre-malignant lesions and conditions. Despite advances in the treatment of OSCC, the 5-year survival rate remains approximately 50% due to inability of early detection of OSCC and precursor lesions. Early detection of oral cancer, especially in the premalignant stage, can decrease mortality and morbidity significantly. This article reviews some clinical, histopathological features and etiopathogenesis of pre-cancerous lesions of the oral cavity and skin of face and lip vermilion. A relevant English literature search in Pubmed, Science Direct, and Google Scholar was performed from 1930 to 2015. Full text of 191 articles met the specific inclusion criteria for this review. PMID:28855922

Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

USGS Publications Warehouse

DeBoer, Jason A.; Pope, Kevin L.

2015-01-01

Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

Speech outcome in young children born with unilateral cleft lip and palate treated with one- or two-stage palatal repair and the impact of early intervention.

PubMed

Raud Westberg, Liisi; Höglund Santamarta, Lena; Karlsson, Jenny; Nyberg, Jill; Neovius, Erik; Lohmander, Anette

2017-10-25

The aim of this study was to describe speech at 1, 1;6 and 3 years of age in children born with unilateral cleft lip and palate (UCLP) and relate the findings to operation method and amount of early intervention received. A prospective trial of children born with UCLP operated with a one-stage (OS) palatal repair at 12 months or a two-stage repair (TS) with soft palate closure at 3-4 months and hard palate closure at 12 months was undertaken (Scandcleft). At 1 and 1;6 years the place and manner of articulation and number of different consonants produced in babbling were reported in 33 children. At three years of age percentage consonants correct adjusted for age (PCC-A) and cleft speech errors were assessed in 26 of the 33 children. Early intervention was not provided as part of the trial but according to the clinical routine and was extracted from patient records. At age 3, the mean PCC-A was 68% and 46% of the children produced articulation errors with no significant difference between the two groups. At one year there was a significantly higher occurrence of oral stops and anterior place consonants in the TS group. There were significant correlations between the consonant production between one and three years of age, but not with amount of early intervention received. The TS method was beneficial for consonant production at age 1, but not shown at 1;6 or 3 years. Behaviourally based early intervention still needs to be evaluated.

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE PAGES

None, None

2016-03-22

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

An early oral health care program starting during pregnancy: results of a prospective clinical long-term study.

PubMed

Meyer, Karen; Geurtsen, Werner; Günay, Hüsamettin

2010-06-01

This study covers phase IV of a prospective clinical long-term study. Objective of this clinical investigation was to analyze the effects of a long-term prevention program on dental and oral health of teenagers at the age of 13 to 14 years. The entire study was subdivided into four phases. Phase I comprised an individual preventive care during pregnancy ("primary-primary prevention"); phase II assessed mothers and their young children until the age of 3 years ("primary prevention"); and in phase III, mothers and children at the age of 6 years were investigated. In phase IV of the study, the oral health of 13- to 14-year-old teenagers was examined (13.4 +/- 0.5 years; n = 29). All phases consisted of an examination, education about oral health care, and treatment based on the concept of an early oral health care promotion. The control group consisted of randomly selected adolescents at the same age (n = 30). The following clinical parameters were assessed: decayed/missing/filled teeth (DMF-T)/decayed, missing, and filled surface teeth index, hygiene index, papilla bleeding index, Periodontal Screening Index, and Streptococcus mutans/Lactobacillus concentration in saliva. The teenagers of the "prevention" group of phase IV of our prospective study revealed a share of 89.7% caries-free dentitions (65.5% sound; 24.2% caries-free with fillings). Mean DMF-T was 0.55 +/- 1.0. The control group showed a significantly higher mean DMF-T of 1.5 +/- 1.5 (p < 0.05) and revealed 56.7% of caries-free dentitions (30% sound, 26.7% caries-free with restorations). Our data clearly document that an early oral health care promotion starting during pregnancy may cause a sustained and long-term improvement of the oral health of children.

Incidence of oral cavity and pharynx cancer in New Hampshire, 1990-2007.

PubMed

Cherala, Sai S; Kelley, Kristina

2012-01-01

The purpose of this study is to describe trends of the statewide cancer and treatment-related characteristics of oral cavity and pharynx (OCP) cancer and prevalence of risk factors in New Hampshire residents from 1990-2007. This is a descriptive study on oral cavity and pharynx cancer using a state cancer registry dataset for 1990- 2007. The age-adjusted rates with 95% confidence intervals for cancer incidence rates and standard proportions for stage, treatment, and risk factors were calculated. The Joinpoint regression model was used for assessing linear trends for cancer rates. The overall differences for the period under study between age, female and male rate, and stage were analyzed using the test. During 1990-2007, oral cavity and pharynx cancer incidence rates for New Hampshire residents have remained stable. The cancer incidence rates have decreased for older age groups (greater than 59) and the 50-59 age group has shown increase in incidence rate of OCP cancer since 1990. There is significant increase in the late-stage diagnoses from 1990-2007. Early detection through periodic medical and dental examinations can reduce the risk of these cancers. Public health strategies that address the gaps identified by this study can reduce OCP cancer and protect the health of the New Hampshire population.

Stage is a prognostic factor for surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status has been implemented.

PubMed

Eskiizmir, G; Ozgur, E; Karaca, G; Temiz, P; Yanar, N Hacioglu; Ozyurt, B Cengiz

2017-10-01

To determine the locoregional control and survival rates (in terms of risk factors) of patients who underwent surgical resection of early-stage lip cancer and for whom a 'wait and see' policy in terms of neck status had been implemented. The sociodemographic data, tumour stage, tumour characteristics and histopathological features of 41 patients with early-stage lip cancer were evaluated. Factors predictive of survival and locoregional recurrence were analysed. The five-year overall survival and disease-free survival rates were determined, and the prognostic risk factors were compared. The mean follow-up period was 60.5 months (range, 4-92 months). Age, sex, tumour stage, tumour thickness and volume, and perineural involvement were not predictive of locoregional recurrence or survival. Pathological tumour stage (T1 vs T2) was a prognostic factor for both five-year overall survival (87.3 vs 65.6 per cent, p = 0.042) and disease-free survival (88.6 vs 65.6 per cent, p = 0.037). Tumour stage was clearly a major factor affecting the prognosis of surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status had been implemented.

Dynamics of laser ablation at the early stage during and after ultrashort pulse

NASA Astrophysics Data System (ADS)

Ilnitsky, D. K.; Khokhlov, V. A.; Zhakhovsky, V. V.; Petrov, Yu V.; Migdal, K. P.; Inogamov, N. A.

2016-11-01

Study of material flow in two-temperature states is needed for a fundamental understanding the physics of femtosecond laser ablation. To explore phenomena at a very early stage of laser action on a metallic target our in-house two-temperature hydrodynamics code is used here. The early stage covers duration of laser pulse with next first few picoseconds. We draw attention to the difference in behavior at this stage between the cases: (i) of an ultrathin film (thickness of order of skin depth d skin or less), (ii) thin films (thickness of a film is 4-7 of d skin for gold), and (iii) bulk targets (more than 10d skin for gold). We demonstrate that these differences follow from a competition among conductive cooling of laser excited electrons in a skin layer, electron-ion coupling, and hydrodynamics of unloading caused by excess of pressure of excited free electrons. Conductive cooling of the skin needs a heat sink, which is performed by the cold material outside the skin. Such sink is unavailable in the ultrathin films.

Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

PubMed

Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

2017-09-01

Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2015-12-01

early stage ovarian cancer to help researchers worldwide identify biomarkers that can aid early detection and inform novel targets for therapy. This...to detect differentially expressed genes after transformation using Voom. When using the top 5 genes to build the classifier, it predicted...to analyze expression of micro-RNA in these samples. Thus, at the end of the third year of funding we started a parallel analysis of RNAseq, DNA- CNV

Hallux abductus interphalangeus in normal feet, early-stage hallux limitus, and hallux valgus.

PubMed

Castillo-Lopez, Jose M; Ramos-Ortega, Javier; Reina-Bueno, Maria; Domínguez-Maldonado, Gabriel; Palomo-Toucedo, Inmaculada C; Munuera, Pedro V

2014-03-01

Excessive deviation of the distal phalanx in abduction frequently occurs in advanced stages of hallux rigidus but not in hallux valgus. Therefore, theoretically there should be no significant differences in the hallux interphalangeal angle (HIPA) between individuals with normal feet, those with hallux valgus, and those with mild hallux limitus. The objective of the present study was thus to determine if significant differences in HIPA exist in the early stages of hallux valgus or hallux limitus deformities. The hallux interphalangeal angle was measured in three groups of participants: a control group with normal feet (45 participants), a hallux valgus group (49 participants), and a hallux limitus group (48 participants). Both of the pathologies were at an early stage. A dorsoplantar radiograph under weightbearing conditions was taken for each individual, and measurements (HIPA and hallux abductus angle [HAA]) were taken using AutoCAD (Autodesk Inc, San Rafael, California) software. Intergroup comparisons of HIPA, and correlations between HIPA, HAA, and hallux dorsiflexion were calculated. The comparisons revealed no significant differences in the values of HIPA between any of the groups (15.2 ± 5.9 degrees in the control group, 15.5 ± 3.9 degrees in the hallux valgus group, and 16.15 ± 4.3 in the hallux limitus group; P  =  0.634). The Pearson correlation coefficients in particular showed no correlation between hallux dorsiflexion, HAA, and HIPA. For the study participants, there were similar deviations of the distal phalanx of the hallux with respect to the proximal phalanx in normal feet and in feet with the early stages of the hallux limitus and hallux valgus deformities.

Cost implications of unwarranted imaging for distant metastasis in women with early-stage breast cancer in Ontario.

PubMed

Thavorn, K; Wang, Z; Fergusson, D; van Katwyk, S; Arnaout, A; Clemons, M

2016-02-01

Despite the publication of multiple evidence-based guidelines recommending against routine imaging for distant metastasis in patients with early-stage (i/ii) breast cancer, such imaging is frequently performed. The present retrospective cohort study was conducted to estimate the cost of unnecessary imaging tests in women with stage i and ii breast cancer diagnosed between 1 January 2007 and 31 December 2012 in Ontario. We obtained patient-level demographic and tumour data from a large provincial dataset. The total cost of unwarranted imaging tests (in 2015 Canadian dollars) was considered to be equal to the sum of imaging costs incurred between 2007 and 2012 and was stratified by disease stage, imaging modality, and body site. Of the 26,547 identified patients with early-stage breast cancer, 22,811 (85.9%) underwent at least 1 imaging test, with an average of 3.7 tests per patient (3.2 for stage i patients and 4.0 for stage ii patients) over 5 years. At least 1 imaging test was performed in 79.6% of stage i and 92.7% of stage ii patients. During a 5-year period, the cost of unwarranted imaging in patients with early-stage breast cancer ranged from CA$4,418,139 to CA$6,865,856, depending on guideline recommendations. Our study highlights the substantial cost of excess imaging that could be saved and re-allocated to patient care if evidence-based guidelines are followed. Future studies should assess strategies to ensure that evidence-based guidelines are followed and to increase awareness of the cost implications of nonadherence to guidelines.

The Prevalence of Canine Oral Protozoa and Their Association with Periodontal Disease.

PubMed

Patel, Niran; Colyer, Alison; Harris, Steve; Holcombe, Lucy; Andrew, Peter

2017-05-01

Periodontal disease is one of the most important health concerns for companion animals. Research into canine forms of periodontitis has focused on the identification and characterization of the bacterial communities present. However, other microorganisms are known to inhabit the oral cavity and could also influence the disease process. A novel, broad spectrum 18S PCR was developed and used, in conjunction with next-generation sequencing analyses to target the identification of protists. Trichomonas sp. and Entamoeba sp. were identified from 92 samples of canine plaque. The overall prevalence of trichomonads was 56.52% (52/92) and entamoebae was 4.34% (4/92). Next-generation sequencing of pooled healthy, gingivitis, early-stage periodontitis, and severe periodontitis samples revealed the proportion of trichomonad sequences to be 3.51% (health), 2.84% (gingivitis), 6.07% (early periodontitis), and 35.04% (severe periodontitis), respectively, and entamoebae to be 0.01% (health), 0.01% (gingivitis), 0.80% (early-stage periodontitis), and 7.91% (severe periodontitis) respectively. Both genera of protists were statistically associated with plaque from dogs with periodontal disease. These findings provide the first conclusive evidence for the presence of oral protozoa in dog plaque and suggest a possible role for protozoa in the periodontal disease process. © 2016 The Author(s) The Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.

Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients.

PubMed

Park, Ji Young; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Kim, Dae-Yeon; Sohn, Insuk; Lee, Shin-Wha; Sung, Chang Ohk; Kim, Kyu-Rae

2013-03-01

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.

Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.

PubMed

Queck, Katherine E; Chapman, Angela; Herzog, Leslie J; Shell-Martin, Tamara; Burgess-Cassler, Anthony; McClure, George David

Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.

Late stages of accumulation and early evolution of the planets

NASA Technical Reports Server (NTRS)

Vityazev, Andrey V.; Perchernikova, G. V.

1991-01-01

Recently developed solutions of problems are discussed that were traditionally considered fundamental in classical solar system cosmogony: determination of planetary orbit distribution patterns, values for mean eccentricity and orbital inclinations of the planets, and rotation periods and rotation axis inclinations of the planets. Two important cosmochemical aspects of accumulation are examined: the time scale for gas loss from the terrestrial planet zone, and the composition of the planets in terms of isotope data. It was concluded that the early beginning of planet differentiation is a function of the heating of protoplanets during collisions with large (thousands of kilometers) bodies. Energetics, heat mass transfer processes, and characteristic time scales of these processes at the early stages of planet evolution are considered.

Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer

ClinicalTrials.gov

2013-05-08

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx

Reproductive and early life stages pathology - Histopathology workshop report

USGS Publications Warehouse

Bruno, D.W.; Nowak, B.; Elliott, Diane G.

2006-01-01

Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

PubMed Central

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

2013-01-01

Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

Estimation of Wheat Plant Density at Early Stages Using High Resolution Imagery

PubMed Central

Liu, Shouyang; Baret, Fred; Andrieu, Bruno; Burger, Philippe; Hemmerlé, Matthieu

2017-01-01

Crop density is a key agronomical trait used to manage wheat crops and estimate yield. Visual counting of plants in the field is currently the most common method used. However, it is tedious and time consuming. The main objective of this work is to develop a machine vision based method to automate the density survey of wheat at early stages. RGB images taken with a high resolution RGB camera are classified to identify the green pixels corresponding to the plants. Crop rows are extracted and the connected components (objects) are identified. A neural network is then trained to estimate the number of plants in the objects using the object features. The method was evaluated over three experiments showing contrasted conditions with sowing densities ranging from 100 to 600 seeds⋅m-2. Results demonstrate that the density is accurately estimated with an average relative error of 12%. The pipeline developed here provides an efficient and accurate estimate of wheat plant density at early stages. PMID:28559901

Efficient and Rapid Isolation of Early-stage Embryos from Arabidopsis thaliana Seeds

PubMed Central

Raissig, Michael T.; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

2013-01-01

In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a method that allows the efficient isolation of young Arabidopsis embryos, yielding up to 40 embryos in 1 hr to 4 hr, depending on the downstream application. Embryos are released into isolation buffer by slightly crushing 250-750 seeds with a plastic pestle in an Eppendorf tube. A glass microcapillary attached to either a standard laboratory pipette (via a rubber tube) or a hydraulically controlled microinjector is used to collect embryos from droplets placed on a multi-well slide on an inverted light microscope. The technical skills required are simple and easily transferable, and the basic setup does not require costly equipment. Collected embryos are suitable for a variety of downstream applications such as RT-PCR, RNA sequencing, DNA methylation analyses, fluorescence in situ hybridization (FISH), immunostaining, and reporter gene assays. PMID:23770918

Effectiveness of a community-based program for suicide prevention among elders with early-stage dementia: A controlled observational study.

PubMed

Kim, Jong-Pill; Yang, Jinhyang

The purpose of this study was to develop a small-group-focused suicide prevention program for elders with early-stage dementia and to assess its effects. This was a quasi-experimental study with a control group pretest-posttest design. A total of 62 elders diagnosed with early-stage dementia who were receiving care services at nine daycare centers in J City Korea participated in this study. The experimental group participated in the suicide prevention program twice a week for 5 weeks with a pretest and two posttests The developed suicide prevention program had a significant effect on the perceived health status, social support, depression, and suicidal ideation of elders with early-stage dementia. Nurses should integrate risk factors such as depression and protective factors such as health status and social support into a suicide prevention program. This community-based program in geriatric nursing practice can be effective in preventing suicide among elders with early-stage dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

The power of personality in discriminating between healthy aging and early-stage Alzheimer's disease.

PubMed

Duchek, Janet M; Balota, David A; Storandt, Martha; Larsen, Randy

2007-11-01

This study examined differences in personality in the earliest stages of dementia of the Alzheimer type (DAT) relative to healthy aging, and the power of personality in discriminating healthy aging from early-stage DAT. Four groups of participants (middle-aged controls, older controls, persons with very mild DAT, and persons with mild DAT) and their families were administered Costa and McCrae's NEO Five-Factor Inventory. On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. Moreover, informant reports of neuroticism and conscientiousness capture substantial unique variance in discriminating healthy aging and very mild DAT, above and beyond standard neuropsychological tests. Discussion focuses on the importance of personality traits as a noncognitive indicator of early-stage DAT.

Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

PubMed

Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

2018-01-24

Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

Recurrence of Early Stage Colon Cancer Predicted by Expression Pattern of Circulating microRNAs

PubMed Central

Shivapurkar, Narayan; Weiner, Louis M.; Marshall, John L.; Madhavan, Subha; Deslattes Mays, Anne; Juhl, Hartmut; Wellstein, Anton

2014-01-01

Systemic treatment of patients with early-stage cancers attempts to eradicate occult metastatic disease to prevent recurrence and increased morbidity. However, prediction of recurrence from an analysis of the primary tumor is limited because disseminated cancer cells only represent a small subset of the primary lesion. Here we analyze the expression of circulating microRNAs (miRs) in serum obtained pre-surgically from patients with early stage colorectal cancers. Groups of five patients with and without disease recurrence were used to identify an informative panel of circulating miRs using quantitative PCR of genome-wide miR expression as well as a set of published candidate miRs. A panel of six informative miRs (miR-15a, mir-103, miR-148a, miR-320a, miR-451, miR-596) was derived from this analysis and evaluated in a separate validation set of thirty patients. Hierarchical clustering of the expression levels of these six circulating miRs and Kaplan-Meier analysis showed that the risk of disease recurrence of early stage colon cancer can be predicted by this panel of miRs that are measurable in the circulation at the time of diagnosis (P = 0.0026; Hazard Ratio 5.4; 95% CI of 1.9 to 15). PMID:24400111

Early stages in the biogenesis of eukaryotic β-barrel proteins.

PubMed

Jores, Tobias; Rapaport, Doron

2017-09-01

The endosymbiotic organelles mitochondria and chloroplasts harbour, similarly to their prokaryotic progenitors, β-barrel proteins in their outer membrane. These proteins are encoded on nuclear DNA, translated on cytosolic ribosomes and imported into their target organelles by a dedicated machinery. Recent studies have provided insights into the import into the organelles and the membrane insertion of these proteins. Although the cytosolic stages of their biogenesis are less well defined, it is speculated that upon their synthesis, chaperones prevent β-barrel proteins from aggregation and keep them in an import-competent conformation. In this Review, we summarize the current knowledge about the biogenesis of β-barrel proteins, focusing on the early stages from the translation on cytosolic ribosomes to the recognition on the surface of the organelle. © 2017 Federation of European Biochemical Societies.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

USGS Publications Warehouse

Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

2014-01-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

PubMed

Duffy, T A; Iwanowicz, L R; McCormick, S D

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

A review of research on salivary biomarkers for oral cancer detection

PubMed Central

2014-01-01

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non-invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five-year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up-to-date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon—and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non-cancerous disease activity. PMID:24564868

3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder

PubMed Central

Andreazza, Ana Cristina; Kapczinski, Flavio; Kauer-Sant’Anna, Marcia; Walz, Julio C.; Bond, David J.; Gonçalves, Carlos A.; Young, L. Trevor; Yatham, Lakshmi N.

2009-01-01

Background There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder. Methods We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale. Results We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups. Limitations Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world. Conclusion Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder. PMID:19568477

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

PubMed

Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

2017-06-01

Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen ( r = -0.23, p < 0.05) and eGFR ( r = -0.36, p < 0.05). FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

PubMed

Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

2014-12-01

In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

[Frequency of oral squamous cell carcinoma and oral epithelial dysplasia in oral and oropharyngeal mucosa in Chile].

PubMed

Martínez, Carolina; Hernández, Marcela; Martínez, Benjamín; Adorno, Daniela

2016-02-01

Oral cancer in Chile corresponds approximately to 1.6% of all cancer cases. There are few studies about oral epithelial dysplasia and oral squamous cell carcinoma in the Chilean population. To determine the frequency of hyperkeratosis, mild, moderate and severe oral epithelial dysplasia, in situ carcinoma and squamous cell carcinoma of the oral and oropharyngeal mucosa in a registry of the Oral Pathology Reference Institute of the Faculty of Dentistry, Universidad de Chile, in a ten years period. Review of clinical records and pathological plates of 389 patients, obtained between 1990 and 2009. Cases were selected according to their pathological diagnosis, including hyperkeratosis, oral epithelial dysplasia, in situ carcinoma, squamous cell carcinoma and verrucous carcinoma. Forty four percent of cases were squamous cell carcinoma, followed by hyperkeratosis in 37% and mild epithelial dysplasia in 11%. Squamous cell carcinoma was more common in men aged over 50 years. Most of the potentially malignant disorders presented clinically as leukoplakia and squamous cell carcinoma were clinically recognized as cancer. In this study, men aged over 50 years are the highest risk group for oral cancer. Early diagnosis is deficient since most of these lesions were diagnosed when squamous cell carcinoma became invasive. Leukoplakia diagnosis is mostly associated with hyperkeratosis and epithelial dysplasia, therefore biopsy of these lesions is mandatory to improve early diagnosis.

Fluorescence detection of oral squamous cell carcinoma using Hyperflav

NASA Astrophysics Data System (ADS)

Melnik, Ivan S.; Dets, Sergiy M.; Rawicz, Andrew H.; Zhang, Lewei

2000-05-01

A novel hypericin-based drug HyperflavTM has been evaluated for light-induced fluorescence detection of oral cancer. Squamous cell carcinoma was induced with carcinogenic agent in right pouches of forty hamsters (20/20 males/females). Solution of HyperflavTM was sprinkled into stomach with a single dose 0.2 - 4 mg of pure hypericin per kg b.w. and 4 - 8 hours before fluorescence analysis. In two animal groups with cancer symptoms the autofluorescence and hypericin-induced fluorescence were taken under 442 nm excitation. The buccal mucosa and adjacent areas were measured fiberoptically in-vivo and in-vitro using orange/green ratio (610/540). The in-vivo fluorescence imaging of malignant areas was conducted to assist the biopsy guidance and to compare with white-light images. Histological and morphological analyses were performed from biopsies. Oral squamous cell carcinoma in its early stage demonstrated specific higher 610/540 ratio for 37 tested hamsters. Advanced state involved another higher fluorescence maximum around 640 nm that in our opinion caused by strong porphyrin-induced native fluorescence. Such deformation of fluorescence spectra may lead to inadequate perception of diseased tissue area. To avoid this problem the autofluorescence spectra & images were added. HyperflavTM application is promising for demarcation of early oral cancer when combined with autofluorescence measurements.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

PubMed Central

Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

2016-01-01

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

PubMed Central

Woodward, Neil D.; Heckers, Stephan

2015-01-01

Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

PubMed Central

TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

2015-01-01

SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

PubMed

Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

2015-01-01

The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

Hydrodynamic instability of elastic-plastic solid plates at the early stage of acceleration.

PubMed

Piriz, A R; Sun, Y B; Tahir, N A

2015-03-01

A model is presented for the linear Rayleigh-Taylor instability taking place at the early stage of acceleration of an elastic-plastic solid, when the shock wave is still running into the solid and is driven by a time varying pressure on the interface. When the the shock is formed sufficiently close to the interface, this stage is considered to follow a previous initial phase controlled by the Ritchmyer-Meshkov instability that settles new initial conditions. The model reproduces the behavior of the instability observed in former numerical simulation results and provides a relatively simpler physical picture than the currently existing one for this stage of the instability evolution.

Early stages of zeolite growth

NASA Astrophysics Data System (ADS)

Kumar, Sandeep

Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

The temporal characteristics of the early and late stages of the L- and M-cone pathways that signal color

PubMed Central

Petrova, Daniela; Henning, G. Bruce; Stockman, Andrew

2013-01-01

Flickering long-wavelength light appears more yellow than steady light of the same average intensity. The hue change is consistent with distortion of the visual signal at some nonlinear site (or sites) that produces temporal components not present in the original stimulus (known as distortion products). We extracted the temporal attenuation characteristics of the early (prenonlinearity) and late (post-nonlinearity) filter stages in the L- and M-cone chromatic pathway by varying the input stimulus to manipulate the distortion products and the measuring of the observers' sensitivity to them. The early, linear, filter stage acts like a band-pass filter peaking at 10–15 Hz with substantial sensitivity losses at both lower and higher frequencies. Its characteristics are consistent with nonlinearity being early in the visual pathway but following surround inhibition. The late stage, in contrast, acts like a low-pass filter with a cutoff frequency around 3 Hz. The response of the early stage speeds up with radiance, but the late stage does not. A plausible site for the nonlinearity, which modelling suggests may be smoothly compressive but with a hard limit at high input levels, is after surround inhibition from the horizontal cells. PMID:23457358

Socioeconomic Factors Are Associated With Readmission After Lobectomy for Early Stage Lung Cancer.

PubMed

Medbery, Rachel L; Gillespie, Theresa W; Liu, Yuan; Nickleach, Dana C; Lipscomb, Joseph; Sancheti, Manu S; Pickens, Allan; Force, Seth D; Fernandez, Felix G

2016-11-01

Data regarding risk factors for readmissions after surgical resection for lung cancer are limited and largely focus on postoperative outcomes, including complications and hospital length of stay. The current study aims to identify preoperative risk factors for postoperative readmission in early stage lung cancer patients. The National Cancer Data Base was queried for all early stage lung cancer patients with clinical stage T2N0M0 or less who underwent lobectomy in 2010 and 2011. Patients with unplanned readmission within 30 days of hospital discharge were identified. Univariate analysis was utilized to identify preoperative differences between readmitted and not readmitted cohorts; multivariable logistic regression was used to identify risk factors resulting in readmission. In all, 840 of 19,711 patients (4.3%) were readmitted postoperatively. Male patients were more likely to be readmitted than female patients (4.9% versus 3.8%, p < 0.001), as were patients who received surgery at a nonacademic rather than an academic facility (4.6% versus 3.6%; p = 0.001) and had underlying medical comorbidities (Charlson/Deyo score 1+ versus 0; 4.8% versus 3.7%; p < 0.001). Readmitted patients had a longer median hospital length of stay (6 days versus 5; p < 0.001) and were more likely to have undergone a minimally invasive approach (5.1% video-assisted thoracic surgery versus 3.9% open; p < 0.001). In addition to those variables, multivariable logistic regression analysis identified that median household income level, insurance status (government versus private), and geographic residence (metropolitan versus urban versus rural) had significant influence on readmission. The socioeconomic factors identified significantly influence hospital readmission and should be considered during preoperative and postoperative discharge planning for patients with early stage lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Using NanoSIMS coupled with microfluidics to visualize the early stages of coral infection by Vibrio coralliilyticus.

PubMed

Gibbin, E; Gavish, A; Domart-Coulon, I; Kramarsky-Winter, E; Shapiro, O; Meibom, A; Vardi, A

2018-04-20

Global warming has triggered an increase in the prevalence and severity of coral disease, yet little is known about coral/pathogen interactions in the early stages of infection. The point of entry of the pathogen and the route that they take once inside the polyp is currently unknown, as is the coral's capacity to respond to infection. To address these questions, we developed a novel method that combines stable isotope labelling and microfluidics with transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS), to monitor the infection process between Pocillopora damicornis and Vibrio coralliilyticus under elevated temperature. Three coral fragments were inoculated with 15 N-labeled V. coralliilyticus and then fixed at 2.5, 6 and 22 h post-inoculation (hpi) according to the virulence of the infection. Correlative TEM/NanoSIMS imaging was subsequently used to visualize the penetration and dispersal of V. coralliilyticus and their degradation or secretion products. Most of the V. coralliilyticus cells we observed were located in the oral epidermis of the fragment that experienced the most virulent infection (2.5 hpi). In some cases, these bacteria were enclosed within electron dense host-derived intracellular vesicles. 15 N-enriched pathogen-derived breakdown products were visible in all tissue layers of the coral polyp (oral epidermis, oral gastrodermis, aboral gastrodermis), at all time points, although the relative 15 N-enrichment depended on the time at which the corals were fixed. Tissues in the mesentery filaments had the highest density of 15 N-enriched hotspots, suggesting these tissues act as a "collection and digestion" site for pathogenic bacteria. Closer examination of the sub-cellular structures associated with these 15 N-hotspots revealed these to be host phagosomal and secretory cells/vesicles. This study provides a novel method for tracking bacterial infection dynamics at the levels of the tissue and single cell

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

PubMed

Neyt, Mattias; Huybrechts, Michel; Hulstaert, Frank; Vrijens, France; Ramaekers, Dirk

2008-08-01

Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

The effects of parasites on the early life stages of a damselfish

NASA Astrophysics Data System (ADS)

Sun, D.; Blomberg, S. P.; Cribb, T. H.; McCormick, M. I.; Grutter, A. S.

2012-12-01

Early life history traits, such as larval growth, influence the success of coral reef fish in the transition from the larval to the juvenile life phase. Few studies, however, have examined the relationship between parasites and growth in the early life history stages of such fishes. This study examined how parasite prevalence (% infected) and load, and the relationship between parasite presence and fish growth, differed among life stages of the damselfish Pomacentrus amboinensis. Parasite prevalence decreased significantly between the larval stage, which was sampled immediately before settlement on the reef (97 %) and recently settled juveniles (60 %); prevalence was also high for 4-month-old juveniles (90 %), 7-month-old juveniles (100 %) and adult fish (100 %). Total numbers of parasites per fish decreased dramatically (fourfold) between larval and recently settled fish, and then increased in the older stages to levels similar to those observed in larvae, but they did so more gradually than did prevalence. One explanation for these patterns is that heavily infected larvae were preferentially removed from the population during or soon after settlement. Daily fish growth, determined from otolith increments, revealed that growth did not differ between parasitised and non-parasitised larval fish, whereas recently settled fish that were parasitised had faster growth; these parasitised recently settled fish also displayed faster growth prior to settlement. These data provide evidence that parasites may explain some of the variation in growth and survival observed among coral reef fishes after settlement and thereby have a greater impact on population dynamics than previously understood.

SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, X; Wu, J; Cui, Y

2016-06-15

Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independentmore » validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.« less

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

PubMed

Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

2018-05-01

The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

On the role of extracellular polymeric substances during early stages of Xylella fastidiosa biofilm formation.

PubMed

Lorite, Gabriela S; de Souza, Alessandra A; Neubauer, Daniel; Mizaikoff, Boris; Kranz, Christine; Cotta, Mônica A

2013-02-01

The structural integrity and protection of bacterial biofilms are intrinsically associated with a matrix of extracellular polymeric substances (EPS) produced by the bacteria cells. However, the role of these substances during biofilm adhesion to a surface remains largely unclear. In this study, the influence of EPS on Xylella fastidiosa biofilm formation was investigated. This bacterium is associated with economically important plant diseases; it presents a slow growth rate and thus allows us to pinpoint more precisely the early stages of cell-surface adhesion. Scanning electron microscopy and atomic force microscopy show evidence of EPS production in such early stages and around individual bacteria cells attached to the substrate surface even a few hours after inoculation. In addition, EPS formation was investigated via attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal EPS formation already during the early stages of X. fastidiosa biofilm formation, thereby providing supporting evidence for the hypothesis of the relevance of the EPS contribution to the adhesion process. Copyright © 2012 Elsevier B.V. All rights reserved.

Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

NASA Astrophysics Data System (ADS)

Tang, Qixiang; Yu, Tzuyang

2017-04-01

In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population.

PubMed

Elango, Kalavathy Jayapal; Anandkrishnan, Nitin; Suresh, Amritha; Iyer, Subramania K; Ramaiyer, Sundaram Karimassery; Kuriakose, Moni Abraham

2011-07-01

Oral cancer is a potentially preventable disease due to its association with well-known risk factors and easy detectability. There is a significant deficiency in the awareness of oral cancer and its risk factors among the public. Raising public awareness could effectively contribute to achieving a significant reduction in the incidence of oral cancer. The objective of this study was to evaluate the effectiveness of mouth self-examination (MSE) in improving the awareness of oral cancer and its risk factors as well as test its feasibility as an oral cancer-screening tool. The study was carried out in a high-risk population of 57,704 from India, of which, 34,766 individuals who have met the eligibility criteria formed the study population. MSE brochures and trained health workers were employed for the purpose of health education and cancer screening. The present study compared their efficacy to detect oral lesions. Subjects with suspicious lesions were referred to the trained oral cancer specialist for confirmation. A questionnaire to assess the awareness of oral cancer and its risk factors was developed and validated. SPSS (v.11.0) was used for data analysis. The program identified 216 cases of potentially malignant lesions as well as three cases of oral cancer. The findings of MSE and health workers showed 72% concordance, while that of health workers and oral cancer specialist showed 100% concordance. MSE had a low sensitivity of 18%, while the specificity was 99.9%. Though the technique identified high-risk lesions such as red patches (66.7%) and non-healing ulcers (42.9%), the detection rate of white patches was low (12.7%). Overall awareness of oral cancer and its risk factors after introduction of MSE program was over 80%; but the compliance to seek treatment was poor (32%). Mouth self-examination may be used as an effective tool to improve the awareness of oral cancer and for the early detection of lesions. Copyright © 2011 Elsevier Ltd. All rights reserved.

HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage.

PubMed

Ma, Teng; Chen, Xinrong; Ouyang, Hongsheng; Liu, Xiaohui; Ouyang, Ting; Peng, Zhiyuan; Yang, Xin; Chen, Fuwang; Pang, Daxin; Bai, Jieying; Ren, Linzhu

2017-02-02

Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. Copyright © 2016 Elsevier B.V. All rights reserved.