Outpatient, dental care of adult vulnerable patients under general anaesthesia-a retrospective evaluation of need for treatment and dental follow-up care.

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.

Chewing function and related parameters as a function of the degree of dementia: Is there a link between the brain and the mouth?

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.

Interrater reliability and concurrent validity of oral/dental items in the resident assessment instrument minimum data set 2.0.

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.

Influence of cognitive impairment and dementia on oral health and the utilization of dental services : Findings of the Oral Health, Bite force and Dementia Study (OrBiD).

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 .

Non-contact monitoring of agitation and use of a sheltering device in patients with dementia in emergency departments: a feasibility study.

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).

Mild-to-Moderate Chronic Kidney Disease and Geriatric Outcomes: Analysis of Cross-Sectional Data from the Berlin Aging Study II.

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.

Validation of a New Measuring Instrument for the Assessment of Bite Force.

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.

Sorafenib, but not sunitinib, induces regulatory T cells in the peripheral blood of patients with metastatic renal cell carcinoma.

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.

Sexual dimorphism in teeth? Clinical relevance.

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.

What Counts for the Old and Oldest Old?-An Analysis of Patient Criteria for Choosing a Dentist-Part I: Awareness and Selection Criteria, Infrastructure, and Dental Office Equipment.

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.

What Counts for the Old and Oldest Old?-An Analysis of Patient Criteria for Choosing a Dentist-Part II: Personal Characteristics and Soft Skills.

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.

Student Perceptions of Age and Ageing-An Evaluation of Swiss Dental Students Receiving Education in Gerodontology.

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.

Impact of an Oral Hygiene Intervention in People with and without Dementia on Oral Health Parameters-Results from the Oral Health, Bite Force, and Dementia (OrBiD) Pilot Study.

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.

Immediate versus conventional loading of palatal implants in humans: a first report of a multicenter RCT.

This study aims to analyze the clinical performance of two loading concepts on second-generation palatal implants (Orthosystem, Straumann, Basel, Switzerland) in a prospective multicenter randomized controlled clinical trial. At the time of this interim analysis, 41 patients have been randomized on a 1:1 basis to one of two treatment groups. Group 1 underwent conventional loading of palatal implants after a healing period of 12 weeks (gold standard) while group 2 underwent immediate implant loading within 1 week after implant insertion. We report initial results at 6 months after functional loading. The primary outcome parameter was implant success (no implant mobility, no implant loss). The implants in both groups were initially stable at the time of insertion, and all were eligible for randomization. Twenty-two patients (group 1) were subjected to conventional implant loading after 12 weeks while 19 patients (group 2) received immediate functional loading within the first week after insertion. Direct (e.g. distal jet appliances) as well as indirect forms of anchorage (conventional or modified transpalatal arch) were used. The magnitude of orthodontic forces ranged between 1 and 4 N for the immediate loading group and between 1 and 5 N for the conventional loading group. One implant in group 1 was lost during the healing phase. One dropout was registered in group 2. Thirty-nine implants were functionally loaded for over 6 months now. These preliminary data provide first evidence of the fact that immediate loading of palatal implants yields equivalent success rates as conventional loading to 4 N after 6 months.

Dental care of frail older people and those caring for them.

AIMS AND OBJECTIVES: To describe oral health utilisation patterns of frail older people and contrast these with attitudes and utilisation patterns of nursing staff who are caring for them. BACKGROUND: In view of widespread poor oral health of frail older people in long-term care, staff attitudes have been identified as an area of interest. In addition to data on attitudes, the current study contributes a description of aspects of oral health related behaviour of staff and clients. DESIGN: Cross-sectional study. METHODS: Structured interviews of a random selection of long-term care staff (n=320) and frail older people (n=172), within the two groups of home-care services (HCS) and long-term care facilities (LTCF). RESULTS: Of staff members, 55·3% attach the same importance to their own oral health compared to that of clients and 35·7% regard their own oral health as more important; 98·4% of staff attended two or more dental examinations per year; 3·4% of HCS and 37·1% of LTCF routinely arranged oral examinations. In 81·4% HCS and in 34·4% of LTCF, there was no routine dental service available. Patterns of oral health service attendance greatly differ between staff and clients. CONCLUSION: The oral health awareness of the majority of long-term care staff did not translate into adequate oral health care for clients. A gap exists between attitudes supportive of oral health, adequate and prevention driven own oral health related behaviour of staff and actual oral health care delivered to clients. RELEVANCE TO CLINICAL PRACTICE: To bridge the gap identified, a concept is suggested for nursing educators and managers of LTCF targeting educational measures while taking into account individual attitudes.

Epigenetic Clock and Relative Telomere Length Represent Largely Different Aspects of Aging in the Berlin Aging Study II (BASE-II).

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.

A new combined flow-cytometry-based assay reveals excellent activity against Toxoplasma gondii and low toxicity of new bisphosphonates in vitro and in vivo.

OBJECTIVES: The aim of this study was to investigate the antiparasitic activity and toxicity of bisphosphonates using a new combined flow cytometry assay. METHODS: Using Toxoplasma gondii tachyzoites carrying the green-fluorescent protein (GFP), we established a new flow cytometry assay combining testing of in vitro and in vivo activity plus toxicity of newly synthesized bisphosphonates against T. gondii. Toxicity as determined by this assay was compared with toxicity as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. RESULTS: In vivo, therapeutic efficacy was 100% for bisphosphonates 2F, 3B, 18A, 22A and 30B at 490, 1000, 512, 44.05 and 47.6 microM concentrations, respectively. Toxicity at 100% inhibitory concentrations was 20% for 2F and 3B, 60% for 22A and 30B, and 75% for 18A. In vitro, 6 (91A, 203A, 200C, 210A, 204A and 282A) of 15 newly synthesized bisphosphonates (12 nitrogen-containing and 3 n-alkyl) inhibited parasite replication by >50% at a concentration of 100 microM. Whereas substances 91A and 282A (high efficacy) showed moderate and low toxicity (cell viability between 70% and 100%), respectively, toxicities of 203A, 200C, 210A and 204A were 70%, 65%, 80% and 70%, respectively, as determined by flow cytometry. Compounds 290A, 218A, 214A, 266A and 219A inhibited parasite replication by between 20% and 50% at a concentration of 100 microM. CONCLUSIONS: Newly synthesized bisphosphonates 2F, 3B, 91A and 282A showed excellent therapeutic activity and low toxicity. These antiparasitic drugs may therefore be promising compounds for use in patients with acute and reactivated toxoplasmosis. The new flow cytometry assay allowed simultaneous determination of therapeutic efficacy and toxicity.

Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques.

OBJECT: The use of dural grafts is frequently unavoidable when tension-free dural closure cannot be achieved following neurosurgical procedures or trauma. Biodegradable collagen matrices serve as a scaffold for the regrowth of natural tissue and require no suturing. The aim of this study was to investigate the efficacy and safety of dural repair with a collagen matrix using different fixation techniques. METHODS: A total of 221 patients (98 male and 123 female; mean age 55.6 +/- 17.8 years) undergoing cranial (86.4%) or spinal (13.6%) procedures with the use of a collagen matrix dural graft were included in this retrospective study. The indications for use, fixation techniques, and associated complications were recorded. RESULTS: There were no complications of the dural graft in spinal use. Five (2.6%) of 191 patients undergoing cranial procedures developed infections, 3 of which (1.6%) were deep infections requiring surgical revision. There was no statistically significant relationship between the operative field status before surgery and the occurrence of a postoperative wound infection (p = 0.684). In the 191 patients undergoing a cranial procedure, cerebrospinal fluid (CSF) collection occurred in 5 patients (2.6%) and a CSF fistula in 5 (2.6%), 3 of whom (1.6%) required surgical revision. No patient who underwent an operation with preexisting CSF leakage had postoperative CSF leakage. Postoperative infection significantly increased the risk for postoperative CSF leakage. The collagen matrix was used without additional fixation in 124 patients (56.1%), with single fixation in 55 (24.9%), and with multiple fixations in 42 (19%). There were no systemic allergic reactions or local skin changes. Follow-up imaging in 112 patients (50.7%) revealed no evidence of any adverse reaction to the collagen graft. CONCLUSIONS: The collagen matrix is an effective and safe cranial and spinal dural substitute that can be used even in cases of an existing local infection. Postoperative deep infection increases the risk for CSF leakage.

The hSNM1B/Apollo variant rs11552449 is associated with cellular sensitivity towards mitomycin C and ionizing radiation.

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.

The prognostic significance of determining DNA content in breast cancer by DNA image cytometry: the role of high grade aneuploidy in node negative breast cancer.

AIM: To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers. METHODS: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content >5c) and highly aneuploid cells (DNA content >9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cut-off value of >10 aneuploid cells (>5c) and of >1 highly aneuploid cell (>9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS). RESULTS: Subgroups among patients with breast cancer with aneuploid cells below the cut-off value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with >10 aneuploid cells (>5c) and >1 highly aneuploid cell (>9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with <10 aneuploid cells (>5c) and <1 highly aneuploid tumour cell (>9c) in DFS and OS. CONCLUSION: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy.