Defining the dimensions of circulating tumor cells in a large series of breast,prostate, colon,and bladder cancer patients

Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch^® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch^® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.

Abbreviations

ACCEPT

Automated CTC Classification, Enumeration, and PhenoTyping software

BC

breast cancer

BLC

bladder cancer

CD

computed diameter

CEL

cultured tumor cell (cell line)

CK

cytokeratin

CRC

colorectal cancer

CTC‐L

circulating tumor cells derived from cerebrospinal fluid (liquor)

CTCs

circulating tumor cells

DAPI

4′6‐diamidino‐2‐phenylindole

EMT

epithelial–mesenchymal transition

EpCAM

epithelial cell adhesion molecule

IQR

interquartile range

KW test

Kruskal–Wallis test

MWU test

Mann–Whitney U test

NCR

nucleus/cytoplasm ratio

P2A

perimeter to area

PC

prostate cancer

TIF

tagged Image Format files

TXT

text file

μm

micrometer

µm²

square micrometers

     

Mind the gap: Teachers’ conceptions of student-staff partnership and its potential to enhance educational quality

Abstract

Introduction: Student-staff partnerships as a concept to improve medical education have received a growing amount of attention. Such partnerships are collaborations in which students and teachers seek to improve education by each adding their unique contribution to decision-making and implementation processes. Although previous research has demonstrated that students are favourable to this concept, teachers remain hesitant. The present study investigated teachers’ conceptions of student-staff partnerships and of the prerequisites that are necessary to render such partnerships successful and enhance educational quality.

Method: We conducted semi-structured interviews with 14 course coordinators who lead course design teams and also teach in 4 bachelor health programmes, using Bovill and Bulley’s levels of student participation as sensitising concepts during data analysis.

Results: The results pointed to three different conceptions of student-staff partnerships existing among teachers: Teachers teach and students study; teachers teach and value students’ feedback; and teachers and students co-create. The prerequisites for effective co-creation teachers identified were: Teachers must be open to involve students and create dialogues; students must be motivated and have good communication skills; the organisation must be supportive; and teachers should have the final say.

Conclusion: We conclude that teachers’ conceptions are consistent with Bovill and Bulley’s levels of student participation. Under certain conditions, teachers are willing to co-create and reach the highest levels of student participation.     

Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration

The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α‐synuclein‐related condition, such as Parkinson’s disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson’s disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α‐synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson’s disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson’s disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson’s disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self‐reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α‐synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder‐associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson’s disease.     

Economic impact of dental service utilization by older adults

A total of 747 general dental practitioners--in Arizona, Colorado, Connecticut, Florida, and Minnesota--responded to a questionnaire in 1988 by completing a detailed productivity report of patient services performed during a specified period. The results, based on 11,909 patient visits and 22,712 dental procedures, indicated that stereotypes of older adults as underutilizers of dental care are incorrect. This finding and others, detailed within this article, indicate that older adults make up a substantial portion of regular patients and that their utilization of dental services should increase throughout 1990.     

A histomorphometric analysis of heavily loaded and non-loaded implants

PURPOSE: To investigate the bone tissue response at the interface of loaded and non-loaded implants used in an orthopedic anchorage system after a continuous, non-axial force application of 5 N over 2 months. MATERIALS AND METHODS: Twenty-nine Br?nemark System implants were placed in the zygomatic arches of 5 dogs. After a healing period of 8 weeks, 20 implants (4 in each dog) were loaded during 8 weeks with a large non-axial orthopedic force application of 5 N. This force was directed between the implants and a maxillary splint to move the maxilla forward. Nine implants were not loaded during this period. At the termination of the experiment, all 29 implants were retrieved for radiographic as well as for histologic analysis. Computer-based histomorphometric quantifications were performed via light microscopy and computer software. Bone-metal contact (BMC), bone surface area (BSA) inside the threads, and the bone mirror area (BMA) of the implants were measured. Statistical comparisons between the loaded and non-loaded implants were carried out. In the group of loaded implants a 2-factor analysis of variance was used. RESULTS: There were no statistically significant differences found in BMC, BSA, and BMA between the loaded and non-loaded implants, both for all the threads and for only the cervical region of the implants. Nor were there statistically significant differences between the non-pressure and pressure sides or for different lengths of the loaded implants. DISCUSSION: The loaded implants maintained the osseointegration achieved during the 8-week healing period. CONCLUSIONS: The results of this study indicate that titanium implants can be used as anchorage for orthopedic force application systems.     

The influence of social indices on oral health and oral health behaviour in a group of Flemish socially deprived adolescents

AIM: To investigate the impact of social indices on oral health and oral health behaviour in socially deprived adolescents and young adults in Flanders. METHOD: The study design was cross-sectional and included 68 subjects aged 12 to 26, who called for help by "Habbekrats", a non-profit organisation rendering assistance to adolescents and young adults living on the fringes of our society. The clinical oral examination was performed using criteria based on the diagnostic criteria for caries prevalence surveys published by BASCD. Information on parental occupational level, educational level, living condition and oral health behaviour was gained using questionnaires completed by the participants themselves and their social workers. RESULTS: The mean age was 16.2 years. Within the sample 92% and 90.8% respectively had a father or mother belonging to a low social level. For 68% of the sample the educational level was low. Concerning oral health behaviour 67% reported nutritional habits conducive to poor oral health whereas 64% reported good oral hygiene habits. The mean DMFS was 11.42 (SD = 14.33) and the mean care-index equalled 0.60 (SD = 0.39). Statistical analysis by means of a logistic regression model revealed that only the 'living condition' had a statistically significant influence on oral health behaviour (p < or = 0.05) and care-index (p < or = 0.05). There was no significant correlation between the parents occupation and subjects' educational level and the oral health behaviour and oral health status of the study group. CONCLUSION: From this analysis it is clear that 'living condition' had a significant influence on the oral health behaviour and care indices of the studied population of socially deprived adolescents.     

Measuring oral health behaviour in Flemish health care workers: an application of the theory of planned behaviour

OBJECTIVE: This study describes the development and validation of a questionnaire to measure the determinants of oral health related behaviour in health care workers, based on the Theory of Planned Behaviour (TPB). RESEARCH DESIGN: A preliminary questionnaire was drafted containing 78 self report items measuring three behaviours related to oral health (i.e. dietary habits, oral hygiene habits and dental attendance), as well as the attitudes, perceived social norms and self-efficacy for each behaviour. The questionnaire was completed by 201 health care workers for the initial validation and 966 other health care workers for a replication. OUTCOMES: A principal component analysis with Procrustes rotation toward an a priori three component structure on the original sample yielded high congruence measures for reported dental attendance, but not for dietary habits and oral hygiene habits. Subsequent exploratory Varimax rotations and discarding of redundant items resulted in three component solutions explaining 43% of the variance in dietary habits, 57% in oral hygiene habits and 66% in dental attendance, respectively. For all three behaviours, these components corresponded to the dimensions of the TPB. Internal consistency of the scales was satisfactory, with Chronbach's alpha's ranging from 0.51 to 0.87. Scale scores accounted for a significant proportion of the variance in the intention to avoid sweet snacks, to brush teeth, and to attend dental check-ups, and of the frequency of consumption of sweet drinks and frequency of brushing. A confirmatory factor analysis on the larger sample of 966 health care workers provided excellent goodness of fit indices, confirming the construct validity of the scales.     

Integrated molecular landscape of amyotrophic lateral sclerosis provides insights into disease etiology

Amyotrophic lateral sclerosis (ALS) is a severe, progressive and ultimately fatal motor neuron disease caused by a combination of genetic and environmental factors, but its underlying mechanisms are largely unknown. To gain insight into the etiology of ALS, we here conducted genetic network and literature analyses of the top‐ranked findings from six genome‐wide association studies of sporadic ALS (involving 3589 cases and 8577 controls) as well as genes implicated in ALS etiology through other evidence, including familial ALS candidate gene association studies. We integrated these findings into a molecular landscape of ALS that allowed the identification of three main processes that interact with each other and are crucial to maintain axonal functionality, especially of the long axons of motor neurons, i.e. (1) Rho‐GTPase signaling; (2) signaling involving the three regulatory molecules estradiol, folate, and methionine; and (3) ribonucleoprotein granule functioning and axonal transport. Interestingly, estradiol signaling is functionally involved in all three cascades and as such an important mediator of the molecular ALS landscape. Furthermore, epidemiological findings together with an analysis of possible gender effects in our own cohort of sporadic ALS patients indicated that estradiol may be a protective factor, especially for bulbar‐onset ALS. Taken together, our molecular landscape of ALS suggests that abnormalities within three interconnected molecular processes involved in the functioning and maintenance of motor neuron axons are important in the etiology of ALS. Moreover, estradiol appears to be an important modulator of the ALS landscape, providing important clues for the development of novel disease‐modifying treatments.