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1.
Diagnostics (Basel) ; 13(23)2023 Nov 21.
Article in English | MEDLINE | ID: mdl-38066739

ABSTRACT

BACKGROUND: this study aims to validate two occlusal-force-measuring devices by comparing them to a universal testing machine and assessing their reliability across various dental and prosthetic groups. The research comprised two parts: part 1 assessed the measurement accuracy of the Occlusal Force Meter GM 10® (OFM) (Morita, Nagano Keiki, Higashimagome, Ohta-ku, Tokyo, Japan) and a prototype (PRO) by comparing them to a calibrated universal testing machine (ZWICK). Part 2 involved analyzing the devices' reliability based on clinical bite force measurements from study participants. RESULTS: both devices become more accurate and reliable compared to the ZWICK over time of usage. Additionally, higher deviation from the ZWICK can be observed for higher values of forces applied and vice versa for both devices. The PRO's intraoral alignment influences its mean values compared to the OFM in different dental and prosthetic groups. CONCLUSION: both devices had limitations and required quadratic function calibration, making them suitable only for progression measurements. The study concludes that both the OFM and PRO devices can measure occlusal forces with improved accuracy over time. Intraoral alignment should be considered. Their easy-to-use clinical application would allow a more widespread use of masticatory function diagnosis, which could indicate the need for treatment and improve treatment planning.

2.
Article in English | MEDLINE | ID: mdl-35886163

ABSTRACT

Utilization of a dentist is influenced by many factors. The aim of this study is to present the factors relating to how patients become aware of a dentist, according to which criteria they select the dentist, and which factors in the infrastructure, equipment of dental offices, and human interactions are important for patients. A telephone survey with 466 participants (female 59.9%) in three age groups (ag 1: 35−50 years, ag 2: 70−84 years, ag 3: >85 years) in three German cities was conducted. Data were analyzed with respect to age, gender, and place of residence. Hardly any differences in the selection of the dentist and the selection criteria applied were found between the sexes, the age groups, or the places of residence. Recommendation seems to be the major aspect regarding how patients become aware of or select their dentist (n = 278, 65.6%), while modern technologies, e.g., the internet, play a subordinate role (n = 31, 7.3%). The unimportance of modern technologies increases significantly with the increase in age. As age increases, factors such as infrastructure (e.g., elevator available (ANOVA p < 0.001; Bonferoni correction: significant differences between ag 1 and ag 2 p < 0.001, ag 1 and ag 3 p < 0.001, and ag 2 and ag 3 p = 0.009); accessibility by wheelchair (ANOVA p < 0.001; Bonferoni correction: significant differences between ag 1 and ag 2 p = 0.006; and ag 1 and ag 3 p < 0.001); etc.) and dental office equipment become significantly important and influence the choice of dentist, while the importance of good parking facilities significantly decreased with age (ANOVA p = 0.003; Bonferoni correction: significant differences between ag 1 and ag 3 p = 0.004, and ag 2 and ag 3 p = 0.023). With increasing age, e.g., the importance of a television in the waiting room (ANOVA p = 0.012; Bonferoni correction: significant differences between ag 1 and ag 3 p = 0.014; and ag 2 and ag 3 p = 0.011), a modern waiting room (ANOVA p < 0.001; Bonferoni correction: significant differences between ag 1 and ag 3 p < 0.001; and ag 2 and ag 3 p < 0.001) or the possibility to visualize the oral situation on a screen decreases significantly (ANOVA p < 0.001; Bonferoni correction: significant differences between ag 1 and ag 2 p < 0.001; ag 1 and ag 3 p < 0.001, and ag 2 and ag 3 p < 0.001). If dentists want to welcome and treat older people, they should adapt the accessibility, infrastructure and equipment of their practice to the needs of older people in order to be able to guarantee continuous lifelong dental care regardless of the need for assistance or care.


Subject(s)
Delivery of Health Care , Dental Offices , Adult , Aged , Aged, 80 and over , Dentists , Female , Humans , Middle Aged , Patient Selection
3.
Article in English | MEDLINE | ID: mdl-35886473

ABSTRACT

Soft skills include communication skills and personality traits that are important when choosing a dentist, but other factors within the dental office also seem to be important for patients. The aim of this study is to evaluate factors that are important to people in a dentist as well as characteristics of the ideal dentist and to evaluate possible age-, gender-, and residence of living specific differences. A telephone survey with participants aged 35 years or older (ag­age group: ag 1: 35−50 years, ag 2: 70−84 years, ag 3: >85 years) in three German cities was conducted. Data were analyzed with respect to gender and age. Most of the participants (n = 298, 64.2%), regardless of their own gender, age, or place of residence did not care about the gender of the dentist. In general, the price of the treatment does not play a role in choosing the ideal dentist. Women differ significantly from men in their choice of dentist (ANOVA p < 0.001 (preference of non-smoker), ANOVA p < 0.001 (preference, that the dentist does not smell of smoke, importance of appearance (ANOVA p < 0.001) and psycho-social skills, etc.). As age increases, professional experience and psycho-social competencies are rated as important. With the increase in age, the mean value of the desired years of professional experience increases without significant differences between age groups. The importance of advanced training (ANOVA p < 0.001; Bonferoni correction: significant difference between ag 1 and ag 2 p < 0.001, and ag 1 and ag 3 p < 0.001) decreases with age. Especially for participants aged 70 to 84 years, a relationship of trust is important. Between the places of residence, statistical differences for almost all surveyed items were found (e.g., importance that the dentist speaks the patients' native language ANOVA p < 0.001, Bonferoni correction: significant difference between Berlin and Leipzig, Berlin and Mainz, and Leipzig and Mainz (each p < 0.001), dentist has a specialization ANOVA p < 0.001, Bonferoni correction: significant difference between Berlin and Leipzig and Berlin and Mainz (each p < 0.001), etc.). Dentists should be trained to develop psycho-social skills to meet the special demands of the increasing older population.


Subject(s)
Dentist-Patient Relations , Dentists , Aged, 80 and over , Berlin , Female , Humans , Male , Surveys and Questionnaires
4.
Article in English | MEDLINE | ID: mdl-35742734

ABSTRACT

Society is ageing and the higher number of senior citizens in the total population is a challenge for society and often perceived as a burden. Negative images of old age can lead to ageism and poorer healthcare for older people. The younger generation will have to master these demographic challenges. Therefore, their attitude towards and their perception of the older generation has to be monitored. The aim of this study is to present the images of ageing held by dental students who received education in gerodontology and to assess possible changes between different generations of students over time and separated by gender. An annual, anonymous questionnaire survey was conducted among dental students at the end of the 10th semester each year between 2008 and 2021. The questionnaire surveyed personal attitudes towards ageing, the assessment of seniors, and personal experience with seniors (images of ageing, "Aging Semantic Differential"). In addition to confirming Friedan's phenomenon regarding the assessment of age limits, the present study was able to demonstrate a positive image of ageing in dental students, which has remained almost constant over the years. An education in gerodontology might positively influence student perceptions of age and aging.


Subject(s)
Ageism , Students, Dental , Aged , Aging , Attitude of Health Personnel , Humans , Surveys and Questionnaires , Switzerland
5.
J Clin Med ; 11(5)2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35268447

ABSTRACT

This study aimed to assess the influence of an oral hygiene intervention on oral health, depending on the degree of dementia. A clinical evaluation of oral health parameters (index of decayed, missing, and filled teeth (DMFT-index), periodontal screening index (PSI), oral hygiene index (OHI), and bleeding on probing (BOP)) was performed in 120 subjects assigned to five groups, based on the mini mental state examination (MMSE) at baseline and after 12 months. Each MMSE group (no dementia (noDem, MMSE 28-30), mild cognitive impairment (mCI, MMSE 25-27), mild dementia (mDem, MMSE 18-24), moderate dementia (modDem, MMSE 10-17), and severe dementia (sDem, MMSE ≤ 9)) was split into control (no intervention) and experimental groups (intervention on oral hygiene: increased frequency, daily usage of high-fluoride toothpaste). In total, 99 out of 120 subjects were included in the analysis. The dropout rate was high in subjects with modDem and sDem due to death. In subjects with noDem, mCI, and mDem, no changes in the DMFT were found, but improvements in the OHI, BOP, and PSI were observed. Subjects with modDem or sDem demonstrated a deterioration in DMFT; however, in these patients, OHI improved in all control and experimental groups, BOP improved in the experimental group only, and PSI did not improve at all. The scope of improving oral health parameters by increasing the recall frequency and by continuously using high fluoride toothpaste is at its limits in people with severe dementia. Multidimensional approaches should be sought to improve the oral health of vulnerable older patients.

6.
BMC Oral Health ; 21(1): 399, 2021 08 14.
Article in English | MEDLINE | ID: mdl-34391408

ABSTRACT

BACKGROUND: The aim of this study was to show the influence of cognitive impairment and dementia on oral health and on the utilization of dental services. METHODS: A cross-sectional analyzation of data of the OrBiD (Oral Health, Bite Force and Dementia) pilot study was conducted. 137 subjects were stratified into five dementia groups on the basis of the Mini Mental State Examination (MMSE) (1-no dementia (MMSE 28-30), 2-mild cognitive impairment (MMSE 25-27), 3-mild dementia (MMSE 18-24), 4-moderate dementia (MMSE 10-17), and 5-severe dementia (MMSE < 10)). Information on the utilization of dental services and oral health parameters (DMFT index, degree of restoration, Periodontal Screening Index, Bleeding on Probing, Oral Hygiene Index, Denture Hygiene Index) were collected. RESULTS: An increase in dementia resulted in significant reduction in utilization. Moreover, with increasing cognitive impairment/dementia there was a significant difference in the number of teeth that were decayed, but not in the number of filled or missing teeth or the DMF/T index itself. With increasing dementia, the degree of restoration decreased and oral/denture hygiene deteriorated significantly. Nevertheless, periodontal therapy was required for all subjects independent of their degree of dementia while bleeding on probing was increasing with increasing dementia. CONCLUSIONS: An influence of cognitive impairment and dementia on oral health and on the utilization of dental services was shown. However, no conclusions about the influence of the utilization behavior of people with dementia on oral health parameters can be drawn. Further longitudinal studies are needed. Trial registration ClinicalTrials.gov NCT03775772. Registered 14th December 2018, https://clinicaltrials.gov/ct2/show/NCT03775772 .


Subject(s)
Cognitive Dysfunction , Dementia , Bite Force , Cross-Sectional Studies , Dementia/complications , Dental Care , Humans , Oral Health , Pilot Projects
7.
J Oral Rehabil ; 48(10): 1160-1172, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34288029

ABSTRACT

BACKGROUND: To date, no study has investigated the association between chewing function and related parameters as a function of the degree of dementia using a finer subdivision of the values of the Mini-Mental State Examination (MMSE). OBJECTIVE: This study aimed to investigate the differences in chewing function and related parameters as a function of the degree of dementia. METHODS: An analysis of cross-sectional data obtained from the OrBiD (Oral Health, Bite Force, and Dementia) pilot study was performed. The participants were stratified into five groups based on the outcomes of the MMSE (no dementia, MMSE 28-30; mild cognitive impairment, MMSE 25-27; mild dementia, MMSE 18-24; moderate dementia, MMSE 10-17; severe dementia, MMSE <10). The chewing efficiency, maximum occlusal force and related parameters (number of supporting zones, number of teeth, Eichner index, tooth/denture status, denture quality, and dental treatment needs) were recorded. RESULTS: The MMSE groups showed significantly different chewing efficiencies (p = .003, Jonckheere-Terpstra test) and maximum occlusal forces (p = .003, Jonckheere-Terpstra test), but the number of supporting zones (p = .055, chi-square test) and the number of natural teeth (p = .126, chi-square test) were not different. The Eichner index, tooth/denture status, denture quality and dental treatment need showed no significant associations with the degree of dementia. CONCLUSION: An improvement in the usability of the measurement methods for assessing chewing function in people with dementia is needed. Research involving people with dementia is necessary because the nutritional situation often deteriorates rapidly within a multifactorial system, which includes chewing ability and oral health.


Subject(s)
Dementia , Mastication , Bite Force , Brain , Cross-Sectional Studies , Humans , Mouth , Pilot Projects
8.
Clin Oral Investig ; 25(4): 2407-2417, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32930876

ABSTRACT

OBJECTIVES: To analyse the treatment needs of patients who had received dental treatment under GA and the effectiveness of the treatment provided. MATERIALS AND METHODS: Retrospective chart analysis of adult at risk and vulnerable patients requiring dental treatment under GA (2007-2017). Outcome variables were indications for GA, DMF/T, and type of treatment, failure rates of treated teeth, emergencies and recall intervals after GA. RESULTS: Four hundred fourteen subjects (median age 42 years, range 18-93 years) were assigned to four groups (people with disabilities (pwdis), dementias (pwd), dental phobias (pwph), and addictions/psychosocial disorders (pwapd)) and attended the pre-GA assessment. Of these, 247 subjects (median 37 years, range 18-93 years) were treated under GA, mostly pwdis (n = 154, 69.7%). The main indication for treatment under GA was suspicion of pain (n = 178, 72.1%). Pwd had the highest degree of restoration (46.7%), DMF/T value (23.8), and most missing teeth (5.8). Pwapd had the most decayed teeth (12.9). There was a 12-month recall augmented by 2-4 oral hygiene sessions depending on compliance. The failure rate of all treated teeth was 4%. Two dental emergencies were reported for patients who received a GA. CONCLUSIONS: Dental treatment need was high for adult vulnerable people. The diagnostic groups differed mainly in their subjective reason for need of a GA, their DMF/T, treatment needs and type of treatments performed. Failure and dental emergency rates after GA were low in spite of a recall interval of 12 months. CLINICAL RELEVANCE: Regular annual recalls could avoid dental emergencies in patients requiring treatment under GA.


Subject(s)
Anesthesia, Dental , Dental Caries , Adolescent , Adult , Aftercare , Aged , Aged, 80 and over , Anesthesia, General , Dental Care , Humans , Middle Aged , Outpatients , Retrospective Studies , Young Adult
9.
Gerodontology ; 38(1): 66-81, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33084126

ABSTRACT

OBJECTIVE: To examine interrater reliability and concurrent validity of oral/dental items in the Resident Assessment Instrument Minimum Data Set (RAI-MDS) 2.0. BACKGROUND: RAI-MDS is a standardised instrument used in nursing to determine health status and nursing needs. The extent to which oral/dental items in the RAI-MDS describe dental treatment needs concerning oral health has been questioned. MATERIALS AND METHODS: This study evaluated the interrater reliability (dentist vs. nurse) and validity of oral/dental items in the Swiss version of RAI-MDS 2.0 (areas: K-nutritional status, L-oral/dental status) using professional oral examinations as a benchmark. Data of 168 residents of five long-term care facilities in the canton of Zurich, Switzerland, were collected within 1 year between October 2017 and December 2018. The statistical evaluation used descriptive statistics and Cohen's kappa (95% CI). RESULTS: RAI-MDS items K1a, chewing (κ 0.098, 95% CI: 0.004-0.19); K1c, pain (κ 0.039, 95% CI: -0.03 to 0.11); L1a, debris (κ 0.117, 95% CI: 0.02-0.21); L1c, dental status (κ 0.229, 95% CI: 0.12-0.34); L1d, dental disease (κ 0.129, 95% CI: 0.02-0.24); L1e, periodontal diseases (κ -0.005, 95% CI: -0.07 to -0.03); and L1f, daily cleaning (κ -0.031, 95% CI: -0.05 to -0.01) showed weak or no agreement, whereas L1b, denture status (κ 0.634, 95% CI: 0.52-0.75), showed substantial agreement. CONCLUSION: Oral/dental items in RAI-MDS lack reliability and validity. Recognition of oral health situation/treatment needs by nursing staff does not seem to be possible with the current version of this tool.


Subject(s)
Nursing Homes , Oral Health , Health Status , Humans , Nutritional Status , Reproducibility of Results
10.
BMC Psychiatry ; 20(1): 165, 2020 04 15.
Article in English | MEDLINE | ID: mdl-32295567

ABSTRACT

BACKGROUND: Agitation is common in geriatric patients with cognitive impairment, e.g. in persons with dementia (PWD), who are admitted to an emergency department (ED). It might be a first sign of upcoming delirium and is associated with a higher risk of an unfavorable clinical course. Hence, monitoring of vital signs and enhanced movement as indicators of upcoming agitation is essential in these patients during their stay in the ED. Since PWD rarely tolerate fixed monitoring devices, a novel developed non-contact monitoring system (NCMSys) might represent an appropriate alternative. Aim of this feasibility study was to test the validity of a NCMSys and of the tent-like "Charité Dome" (ChD), aimed to shelter PWD from the busy ED environment. Furthermore, effects of the ChD on wellbeing and agitation of PWD were investigated. METHODS: Both devices were attached to patient's bed. Tests on technical validity and safety issues of NCMSys and ChD were performed at the iDoc institute with six healthy volunteers. A feasibility study evaluating the reliability of the NCMSys with and without the ChD was performed in the real-life setting of an ED and on a geriatric-gerontopsychiatric ward. 19 patients were included, ten males and nine females; mean age: 77.4 (55-93) years of which 14 were PWD. PWD inclusion criteria were age ≥ 55 years, a dementia diagnosis and a written consent (by patients or by a custodian). Exclusion criteria were acute life-threatening situations and a missing consent. RESULTS: Measurements of heart rate, changes in movement and sound emissions by the NCMSys were valid, whereas patient movements affected respiratory rate measurements. The ChD did not impact patients' vital signs or movements in our study setting. However, 53% of the PWD (7/13) and most of the patients without dementia (4/5) benefited from its use regarding their agitation and overall wellbeing. CONCLUSIONS: The results of this feasibility study encourage a future controlled clinical trial in geriatric ED patients, including PWD, to further evaluate if our concept of non-contact measurement of vital signs and movement combined with the "Charité Dome" helps to prevent upcoming agitation in this vulnerable patient group in the ED. TRIAL REGISTRATION: ICTRP: "Charité-Dome-Study - DRKS00014737" (retrospectively registered).


Subject(s)
Dementia , Psychomotor Agitation , Aged , Aged, 80 and over , Dementia/diagnosis , Emergency Service, Hospital , Feasibility Studies , Female , Humans , Male , Psychomotor Agitation/diagnosis , Reproducibility of Results
11.
J Gerontol A Biol Sci Med Sci ; 74(1): 27-32, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30137208

ABSTRACT

DNA methylation age (DNAm age; "epigenetic clock") has recently been described as highly correlated with chronological age. Several studies suggest that DNAm age reflects, at least in part, biological age. Here, we adapted a recently published methylation-sensitive single nucleotide primer extension method for epigenetic age estimation and calculated the DNAm age based on only seven cytosine-phosphate-guanine sites in 1,895 DNA samples of the Berlin Aging Study II. In a second step, we explored the relationship between this new potential measure of biological age with an established marker of biological age, relative leukocyte telomere length (rLTL), in the same cohort. Our results showed a positive and significant correlation between DNAm age estimation and chronological age (N = 1,895, Rs2 = .47), which persisted after adjustment for covariates (sex, leukocyte distribution, alcohol and smoking). We found a significant but weak negative association between DNAm age acceleration and rLTL in linear regression analysis adjusted for age, sex, alcohol and smoking (ß = -0.002, p = .007). Therefore, DNAm age appears to be a promising biomarker in the analysis of phenotypes of aging, which are not (only) related to pathways associated with mitotic age as measured by rLTL.


Subject(s)
Aging/genetics , DNA/genetics , Epigenesis, Genetic , Leukocytes/metabolism , Telomere/genetics , Adult , Aged , Aged, 80 and over , DNA Methylation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Telomere/metabolism , Telomere Homeostasis , Young Adult
12.
DNA Repair (Amst) ; 72: 93-98, 2018 12.
Article in English | MEDLINE | ID: mdl-30262195

ABSTRACT

The polymorphism rs11552449 (c.181C > T, p.His61Tyr) in the hSNM1B/Apollo gene has been repeatedly shown to be associated with an increased risk for breast cancer. The aim of the current study was to investigate the association between rs11552449 and the degree of cellular sensitivity to mitomycin C (MMC) and ionizing radiation (IR). A total of 69 lymphoblastoid cell lines (LCLs) from generally healthy donors were tested for their sensitivity towards MMC and IR in growth inhibition experiments. LCLs heterozygous for rs11552449 were significantly more sensitive to MMC and IR than homozygous cells with the CC genotype (p < 0.05 and p < 0.01 for MMC and IR, respectively) and in the case of MMC also for the TT genotype (p < 0.01). Interestingly, heterozygous CT cells expressed significantly more full length hSNM1B/Apollo mRNA than cells with the homozygous CC (p < 0.0001) or TT genotypes (p < 0.00001). Thus, the observed higher sensitivity of cell lines heterozygous for rs11552449 towards MMC and IR may be a consequence of differential expression of hSNM1B/Apollo associated with rs11552449, a feature which has not been ascribed to this polymorphism before. Interestingly, relative leukocyte telomere length (rLTL) analyzed in a subset of these cells (N = 62) and in leukocytes of N = 1710 Berlin Aging Study II (BASE-II) participants was not associated with rs11552449. The results suggest that hSNM1B/Apollo is causal for the repeatedly reported association between rs11552449 and breast cancer. These results pave the way for further research regarding the clinical impact of rs11552449, e.g. on the clinical outcome of cancer therapy with DNA interstrand crosslinking agents and IR.


Subject(s)
DNA Repair Enzymes/genetics , Mitomycin/pharmacology , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Radiation Tolerance/genetics , Cell Line , Exodeoxyribonucleases , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Genotype , Humans
13.
Gerontology ; 64(2): 118-126, 2018.
Article in English | MEDLINE | ID: mdl-29183010

ABSTRACT

BACKGROUND: Mild-to-moderate chronic kidney disease (CKD G3a) is prevalent in older adults. Substantial evidence suggests that individuals with advanced CKD face a high risk for common geriatric conditions, like functional impairment and cognitive decline, whereas the relationships between mild-to-moderate CKD and functional impairment and cognitive decline, but also poor nutritional status and mood disorders, are still unclear. OBJECTIVE: The aim of this study was to explore associations between mild-to-moderate CKD and impairments in the core domains of geriatric assessment (GA) in a large cohort of community-dwelling older adults. METHODS: This was a cross-sectional analysis of 1,476 participants of the Berlin Aging Study II. Study participants were stratified as to presence or absence of CKD G3a (estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m2 vs. eGFR ≥60 mL/min/1.73 m2). GA comprised the following instruments: the Activities of Daily Living Scale (ADL), the Timed up and Go (TUG), the Tinetti test (Tinetti), the Mini-Mental-State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Mini Nutritional Assessment (MNA). We used logistic regression models to estimate multivariable-adjusted associations between CKD G3a and impairments in the respective domains. RESULTS: A total of 282 subjects with mild-to-moderate CKD (CKD G3a) were identified (19.1%). Overall, the prevalence of impairments identified was higher among subjects with compared to without CKD G3a (21 vs. 15.9%, p = 0.043). In multivariable-adjusted models, CKD G3a was consistently associated with increased odds of an impaired gait performance as to the TUG (adjusted odds ratio 2.06, 95% CI 1.04-4.09). In contrast, on average, individuals with and without CKD G3a did not differ as to their results in the MMSE, the ADL, the MNA, and the GDS. CONCLUSION: GA identified impairments in 21 versus 15.9% of older adults with and without mild-to-moderate CKD, respectively. However, except for an increased likelihood of impaired gait performance (TUG) with mild-to-moderate CKD, we did not find independent associations between mild-to-moderate CKD and geriatric conditions.


Subject(s)
Renal Insufficiency, Chronic/epidemiology , Activities of Daily Living , Aged , Aging/physiology , Aging/psychology , Berlin/epidemiology , Cognitive Dysfunction/complications , Cross-Sectional Studies , Female , Geriatric Assessment , Glomerular Filtration Rate , Humans , Logistic Models , Male , Multivariate Analysis , Prevalence , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology
14.
Atherosclerosis ; 253: 88-93, 2016 10.
Article in English | MEDLINE | ID: mdl-27596133

ABSTRACT

BACKGROUND AND AIMS: Autosomal-dominant familial hypercholesterolemia (FH) is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and a dramatically increased risk to develop cardiovascular disease (CVD). Mutations in three major genes have been associated with FH: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB), and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). Here we investigated the frequency and the spectrum of FH causing mutations in Germany. METHODS: We screened 206 hypercholesterolemic patients, of whom 192 were apparently unrelated, for mutations in the coding region of the genes LDLR, PCSK9 and the APOB [c.10580G > A (p.Arg3527Gln)]. We also categorized the patients according to the Dutch Lipid Clinic Network Criteria (DLCNC) in order to allow a comparison between the mutations identified and the clinical phenotypes observed. Including data from previous studies on German FH patients enabled us to analyse data from 479 individuals. RESULTS: Ninety-eight FH causing variants were found in 92 patients (nine in related patients and 6 patients with two variants and likely two affected alleles), of which 90 were located in the LDLR gene and eight mutations were identified in the APOB gene (c.10580G > A). No mutation was found in the PCSK9 gene. While 48 of the LDLR mutations were previously described as disease causing, we found 9 new LDLR variants which were rated as "pathogenic" or "likely pathogenic" based on the predicted effect on the corresponding protein. The proportions of different types of LDLR mutations and their localization within the gene was similar in the group of patients screened for mutations here and in the combined analysis of 479 patients (current study/cases from the literature) and also to other studies on the LDLR mutation spectrum, with about half of the variants being of the missense type and clustering of mutations in exons 4, 5 and 9. The mutation detection rate in the 35 definite and 45 probable FH patients (according to DLCNC) was 77.1% and 68.9%, respectively. The data show a similar discriminatory power between the DLCNC score (AUC = 0.789 (95% CI 0.721-0,857)) and baseline LDL-C levels (AUC = 0.799 (95% CI = 0.732-0.866)). CONCLUSIONS: This study further substantiates the mutation spectrum for FH in German patients and confirms the clinical and genetic heterogeneity of the disease.


Subject(s)
Genetic Variation , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Mutation , Adult , Alleles , Apolipoproteins B/genetics , Cholesterol, LDL/blood , DNA Mutational Analysis , Exons , Female , Genetic Association Studies , Germany , Humans , Male , Middle Aged , Mutation, Missense , Phenotype , Proprotein Convertase 9/genetics , Proprotein Convertases/genetics , ROC Curve , Receptors, LDL/genetics , Serine Endopeptidases/genetics
15.
Cardiovasc Endocrinol ; 5(1): 14-20, 2016 Mar.
Article in English | MEDLINE | ID: mdl-28392972

ABSTRACT

INTRODUCTION: During the 'Knowing what matters in diabetes: healthier below 7' diabetes campaign, more than 30 000 randomly participating individuals underwent an occasional, voluntary diabetes risk check between 2005 and 2014. METHODS: This campaign aimed to inform individuals in Germany about diabetes mellitus and its complications, the established risk factors for development of type 2 diabetes (T2D), their prevalence and management in the real-life population, the quality of risk factor control and actual disease management in participants with a history of established diabetes mellitus [people with diabetes (PWD)]. Besides demographic characteristics (e.g. sex, age) and anamnestic information (antihypertensive treatment, history of elevated plasma glucose levels, genetic disposition), risk factor assessment included BMI, waist circumference, and lifestyle (physical activity, nutritional habits). The requested information was complemented by direct measurements of blood pressure (BP) (routine), plasma glucose, and HbA1c (voluntary). Between 2005 and 2014, more than 31 000 individuals participated in 45 single campaigns in numerous German cities. Here, we report on the results of the subgroup of participants with known diabetes mellitus. RESULTS: Among the 26 522 individuals with a completed questionnaire participating in the years 2006-2014, 21 055 participants (79.4%) did not have a history of diabetes and 5098 individuals (19.2%) reported being diagnosed with T2D, 369 (1.4%) with type 1 diabetes. The proportion of participants with T2D increased markedly over the years from 13.3 (2006) to 21.7% (2014). The age group older than 64 years was the largest within this subgroup (67.3%), 48.4% men and 51.6% women. The prevalence of overweight or obesity was found in 78% and 69.2% of the PWD. More than 40% of individuals with T2D had no regular physical exercise and more than 15% had unfavorable nutritional habits. In all, 69.9% of participants with T2D had elevated BP as assessed during the campaign or reported treatment with antihypertensive drugs at any time. On average, almost half of PWD (46.3%) had an HbA1c above 7.0%; a significant trend toward higher values over the 10-year period was observed. CONCLUSION: The analysis of PWD participating in the 'Knowing what matters in diabetes: healthier below 7' campaign showed that despite huge efforts in the past, important aspects for progression and complications of T2D mellitus are still not well controlled. This includes lifestyle habits as well as pharmaceutical treatment. Although the participants in this study cannot be considered a representative sample of the German population and occasional measurements without standardization further limit firm conclusions, the BP, plasma glucose, and HbA1c results indicate that a major proportion of PWD have insufficient metabolic and BP control. The marked increase in the proportion of T2D among all participants over time is consistent with the increasing prevalence of T2D mellitus found in many other countries worldwide in the recent decades. Our findings underline the importance of an optimized therapy for further improvement of disease management in those already diagnosed with this common chronic, progressive disease.

16.
Community Dent Oral Epidemiol ; 43(6): 521-31, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26086211

ABSTRACT

OBJECTIVE: Decades of conflict, poverty, and dysfunctional public services have affected people's health in Afghanistan. To estimate treatment needs and guide health initiatives, epidemiologic data are required. Such data are currently unavailable for dental health. The present study assessed caries experience, fluorosis, and oral health behavior in children from Afghanistan. METHODS: We performed a two-stage, school-based cross-sectional study in Herat province in Afghanistan. A total of 1059 children, 369 children aged 6-7, 300 aged 12, and 390 aged 15 years, were sampled. Caries was assessed according to ICDAS, and oral hygiene, dietary habits, and parental economic and educational status evaluated. Prevalence of fluorosis was assessed, and fluoride concentrations in drinking water and in used toothpastes were measured. RESULTS: Mean (SD) number of decayed, missing, or filled teeth was dmft = 4.88 (3.11), DMFT = 2.57 (2.16), and DMFT = 4.04 (3.03) in 6-/7-, 12-, and 15-year-olds, respectively. The majority of lesions in 6-year-olds were cavitated, while 12- and 15-year-olds showed more non- or microcavitated lesions. Most lesions, especially in young children, were untreated. Mean (range) water fluoride concentration was 0.37 (0.19-0.67) ppm. Fluoride concentrations in evaluated toothpastes did not meet internationally recommended levels. The majority of children showed no or minimal fluorosis. Having fluorosis, infrequently consuming sweets, or having a father with high education was associated with low caries experience (dmfs/DMFS < 10), with OR (95% CI) being 0.64 (0.47/0.90), 0.65 (0.44-0.95), and 0.64 (0.47/0.90), respectively. CONCLUSIONS: Examined Afghan children had high unmet dental treatment needs and caries experience. Sufficient access to restorative treatment and prevention measures is urgently required.


Subject(s)
Dental Caries/epidemiology , Fluorosis, Dental/epidemiology , Oral Hygiene/statistics & numerical data , Adolescent , Afghanistan/epidemiology , Child , Cross-Sectional Studies , Drinking Water/chemistry , Female , Fluorides/analysis , Humans , Male , Prevalence , Socioeconomic Factors , Toothpastes/chemistry
17.
Trials ; 16: 11, 2015 Jan 06.
Article in English | MEDLINE | ID: mdl-25560779

ABSTRACT

BACKGROUND: For treating deep caries lesions, selective or stepwise (one- and two-step) incomplete excavation seems advantageous compared with complete caries removal. However, current evidence regarding the success, as defined by not requiring any retreatments, or survival of teeth after different excavations is insufficient for definitive recommendation, especially when treating deciduous teeth. Moreover, restoration integrity has not been comparatively analyzed longitudinally, and neither patients', dentists' or parents' preferences nor the clinical long-term costs emanating from both initial and retreatments have been reported yet. METHODS/DESIGN: The planned study is a prospective multicenter, two-arm parallel group, randomized controlled clinical trial comparing selective and stepwise excavation in deciduous molars with deep, active caries lesions without pulpal symptoms. We will recruit 300 children aged between three and nine-years-old with a minimum of one such molar. Patients participating in another study, or those with systemic diseases, disabilities or known allergies to used materials as well patients with teeth expected to exfoliate within the next 18 months will be excluded. After inclusion, sequence generation will be performed. Initial treatment will follow dental routine. During excavation, leathery, moist and reasonably soft dentin will be left in proximity to the pulp followed by adhesive restoration of the cavity. Afterwards, patients', dentists' and parents' subjective assessment of the treatment will be recorded using visual analogue or Likert scales. Re-examination will be performed after six months, and only then teeth will be allocated to one of the two interventions. Selectively excavated teeth will not be treated further, whilst for stepwise caries removal, a second excavation will be performed until only hard dentin remains. Clinical re-evaluations will be performed after 12, 24 and 36 months. Restorations will be reassessed using modified Ryge criteria. Objectively or subjectively required retreatments will determine success and survival. Retreatments will be evaluated both subjectively and regarding generated costs. DISCUSSION: Based on the results of the trial, decision-making for treating deep caries lesions in deciduous molars based on multiple criteria should be feasible. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02232828 (registered on 29 November 2014).


Subject(s)
Clinical Protocols , Dental Caries/therapy , Molar , Tooth, Deciduous , Data Collection , Data Interpretation, Statistical , Humans , Prospective Studies
18.
Immunol Res ; 58(1): 20-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24272857

ABSTRACT

Flow cytometry-based analysis of T-cell receptor (TCR) repertoires is an essential tool for the detection of clonal T-cell expansions in physiologic and pathologic conditions. Individual T-cell subsets can be investigated based on their surface properties. The aims of our study were to provide reference values for various disease settings and delineate the contribution of individual TCR repertoires to the human T-cell differentiation pathway. We analyzed blood of 66 healthy subjects aged 0 (cord blood) to 72 years. Lymphocyte subpopulations and TCR repertoires were simultaneously explored using antibodies specific to CD3, CD4, CD8, CD45RA, CCR7, CD27, CD57 and a set of 25 antibodies detecting human TCR-Vß chains. Statistical analysis included Wilcoxon, paired t and ANOVA tests. Initially, TCR expansion values were calculated based on the analysis of TCR-Vß distribution on CD4+ and CD8+ T cells. We then established gating strategies and an algorithm for data analysis allowing for discrimination of T-cell subsets and TCR distribution. Dominant TCR expansions were present within effector as opposed to central/effector memory or naive cells, e.g., median TCR-Vß expansion rate was highest on CD45RA+/CCR7- effector CD4+/8+ cells (eight and 11-fold, respectively). Remarkably, TCR expansions were missing (0) or very low (0.5) on CD4+ and CD8+ central memory population, respectively. No significant gender-related variability of TCR repertoires was identified, and significant impact of chronic cytomegalovirus infection was shown. Our results serve as reference for future studies elucidating clonal TCR dominance of T-cell subsets.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Receptors, Antigen, T-Cell/immunology , T-Lymphocyte Subsets/immunology , Adolescent , Adult , Aged , Algorithms , Cell Differentiation/immunology , Child , Child, Preschool , Female , Fetal Blood/cytology , Fetal Blood/immunology , Flow Cytometry , Humans , Immunophenotyping/methods , Infant , Infant, Newborn , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Reference Values , Statistics, Nonparametric , Young Adult
19.
Clin Oral Investig ; 16(2): 395-9, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21547373

ABSTRACT

Many morphometric studies show a sexual dimorphism in human teeth. We wanted to know whether it is possible to determine the sex of an individual if only the anterior teeth are visible. Fifty intraoral photographs showing the front tooth region of female and male individuals (age: from 7 to 75 years) were randomly arranged in actual size on a questionnaire. The lip region was covered in each case. Besides "female" and "male", one was also able to check "?" if undecided. The questionnaires were distributed to 50 expert test persons (dentists, dental technicians, dental assistants, and students of dental medicine) and to 50 laymen and were all returned for evaluation. Although the correct sex was recognized on single photographs to a maximum of 76%, it was incorrect in 69% on other photographs. Altogether, the statistical evaluation showed that in most cases, the sex was only recognized correctly by one half, and incorrect by the other half. It can be concluded that a sexual dimorphism of human teeth-although measurable morphometrically-could not be recognized visually on the basis of photographs of the front tooth region. Neither experts in the field of dentistry nor laymen were able to properly distinguish between male and female teeth.


Subject(s)
Sex Characteristics , Tooth/anatomy & histology , Adolescent , Adult , Aged , Bicuspid/anatomy & histology , Child , Cuspid/anatomy & histology , Dental Assistants , Dental Technicians , Dentists , Female , Humans , Incisor/anatomy & histology , Male , Middle Aged , Odontometry , Photography, Dental , Sex Determination by Skeleton , Students, Dental , Young Adult
20.
Anticancer Drugs ; 23(3): 298-302, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22156795

ABSTRACT

Induction of regulatory T cells (Treg) is an important mechanism leading to tolerance against tumors. Increased levels of Treg have been described in renal cell carcinoma (RCC) patients and seem to correlate with an adverse outcome. Our study aimed to analyze the influence of sorafenib and sunitinib on the frequency of Treg in patients with metastatic RCC (mRCC). Treg were analyzed by flow cytometry in the peripheral blood (PB) of patients (n=19) with histologically confirmed mRCC under treatment with either sunitinib (50 mg/d, n=11) or sorafenib (800 mg/d, n=8). Blood samples were taken before treatment and during the first, second, and third months of therapy. Flow cytometric analysis of PB mononuclear cells was performed using fluorochrome-labeled antibodies against CD3, CD4, CD25, and FOXp3. During the first month of therapy, patients treated with sorafenib showed a significant increase in FOXp3CD3CD4CD25 Treg (13.5 vs. 36.3% of gated cells, P=0.02, or 0.35 vs. 0.49% of total cells) and the ratio FOXp3 T cells/FOXp3 T cells (0.16 vs. 0.56 of gated cells, P=0.02). These elevated levels persisted throughout the treatment period. There was no influence of sunitinib on the frequency of Treg in our cohort of patients. Sorafenib, but not sunitinib, leads to an early and sustained increase in Treg in PB of mRCC patients. In immunoresponsive tumors such as RCC, immunological effects of kinase inhibitors are particularly relevant for the design of combination trials with immunotherapeutic agents. Our study suggests that sorafenib should be avoided in such a therapeutic setting.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Pyrroles/therapeutic use , T-Lymphocytes, Regulatory/drug effects , Adult , Aged , Aged, 80 and over , CD3 Complex/metabolism , CD4 Antigens/metabolism , Carcinoma, Renal Cell/pathology , Female , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Kidney Neoplasms/pathology , Male , Middle Aged , Niacinamide/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Sorafenib , Sunitinib , T-Lymphocytes, Regulatory/metabolism , Treatment Outcome
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