[Geriatric syndromes, multimorbidity and geriatric psychiatry; an integrated perspective]. / Geriatrische syndromen, multimorbiditeit en ouderenpsychiatrie; een geïntegreerd perspectief.

BACKGROUND: The prevalence of geriatric syndromes, frailty and multimorbidity increases in older age, with a negative impact on health outcomes. Little is known on these problems in older adults with psychiatric disorders. AIM: To evaluate the prevalence of geriatric syndromes and multimorbidity in older adults with psychiatric disorders and their impact on treatment outcomes. METHOD: We conducted a pilot study and a case-control study on older adults with medically insufficiently explained symptoms, a prospective cohort study in older adults, acutely admitted to psychiatric wards and a systematic review to evaluate whether geriatric syndromes were considered in RCTs on depression treatment. RESULTS: Unexplained symptoms were often accompanied by frailty, multimorbidity and psychiatric disorders. Older adults who were acutely admitted to psychiatric wards had a high level of multimorbidity, about half of them were frail, and a third undernourished. Frailty and multimorbidity were independent predictors for not being discharged to their own home. Frailty also strongly predicted the 5-year mortality rate. Geriatric syndromes were hardly considered in study design or as secondary outcome in treatment studies on depression in older adults. CONCLUSION: Overall, geriatric problems are highly prevalent among older adults with psychiatric disorders and have a relevant prognostic impact. The complexity of older psychiatric patients is probably best addressed by interdisciplinary, integrated diagnostic and treatment trajectories.

Molecular mobility changes after high-temperature, short-time pasteurization: An extended time-domain nuclear magnetic resonance screening of ewe milk.

This study presents an extensive investigation on the effect of pasteurization on raw whole ewe milk. Milk samples have been analyzed, throughout lactation (from February to July), by time-domain nuclear magnetic resonance (TD-NMR), collecting the characteristic TD-NMR relaxation parameters, proton longitudinal and transverse relaxation times (1H T1 and T2). Collected data aim at integrating previous NMR works, mainly focusing on dairy model systems (casein and whey proteins solutions and gels, reconstituted skim milk) and cheese, with specific reference to the effect of heat treatments. Whole ewe milk, from a single flock (Sarda sheep breed), was daily analyzed both as untreated (raw) and heat treated with a laboratory-scaled high-temperature, short-time treatment (72°C for 15 and 20 s). Moreover, molecular dynamics in milk were investigated by TD-NMR in different periods of lactation for the first time. As a consequence of high-temperature short-time treatment, 1H T1 and T2 consistently shifted to lower values with respect to raw counterparts. Statistical analysis indicated a significant decrease of T2 in treated samples, to an extent dependent on the heat treatment duration. A subset of dedicated experiments demonstrated that the observed T2 shift is largely ascribable to protein molecular rearrangements and, to a lesser extent, to the interaction of fat globules with proteins or other nonfat components (or both). In light of the crucial importance of detecting the application of a heat treatment to milk, the results reported here suggest TD-NMR relaxation parameters were able to describe heat-induced changes in molecular dynamics and interactions of milk components in a water-rich environment. The use of TD-NMR can be considered a potential suitable technique for quality control and assurance practices in the dairy industry. Upon statistical validation of methods, the application of TD-NMR in the dairy industry would take advantage of its low cost, reliability, and robustness.

Liver proteomics of gilthead sea bream (Sparus aurata) exposed to cold stress.

The gilthead sea bream (Sparus aurata, L.) is very sensitive to low temperatures, which induce fasting and reduced growth performances. There is a strong interest in understanding the impact of cold on fish metabolism to foster the development and optimization of specific aquaculture practices for the winter period. In this study, an 8 week feeding trial was carried out on gilthead sea bream juveniles reared in a Recirculated Aquaculture System (RAS) by applying a temperature ramp in two phases of four weeks each: a cooling phase from 18 °C to 11 °C and a cold maintenance phase at 11 °C. Liver protein profiles were evaluated with a shotgun proteomics workflow based on filter-aided sample preparation (FASP) and liquid chromatography-mass spectrometry (LC-ESI-Q-TOF MS/MS) followed by label-free differential analysis. Along the whole trial, sea breams underwent several changes in liver protein abundance. These occurred mostly during the cooling phase when catabolic processes were mainly observed, including protein and lipid degradation, together with a reduction in protein synthesis and amino acid metabolism. A decrease in protein mediators of oxidative stress protection was also seen. Liver protein profiles changed less during cold maintenance, but pathways such as the methionine cycle and sugar metabolism were significantly affected. These results provide novel insights on the dynamics and extent of the metabolic shift occurring in sea bream liver with decreasing water temperature, supporting future studies on temperature-adapted feed formulations. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD011059.

Validation of the Care-Related Quality of Life Instrument in different study settings: findings from The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS).

PURPOSE: Validity is a contextual aspect of a scale which may differ across sample populations and study protocols. The objective of our study was to validate the Care-Related Quality of Life Instrument (CarerQol) across two different study design features, sampling framework (general population vs. different care settings) and survey mode (interview vs. written questionnaire). METHODS: Data were extracted from The Older Persons and Informal Caregivers Minimum DataSet (TOPICS-MDS, www.topics-mds.eu ), a pooled public-access data set with information on >3,000 informal caregivers throughout the Netherlands. Meta-correlations and linear mixed models between the CarerQol's seven dimensions (CarerQol-7D) and caregiver's level of happiness (CarerQol-VAS) and self-rated burden (SRB) were performed. RESULTS: The CarerQol-7D dimensions were correlated to the CarerQol-VAS and SRB in the pooled data set and the subgroups. The strength of correlations between CarerQol-7D dimensions and SRB was weaker among caregivers who were interviewed versus those who completed a written questionnaire. The directionality of associations between the CarerQol-VAS, SRB and the CarerQol-7D dimensions in the multivariate model supported the construct validity of the CarerQol in the pooled population. Significant interaction terms were observed in several dimensions of the CarerQol-7D across sampling frame and survey mode, suggesting meaningful differences in reporting levels. CONCLUSIONS: Although good scientific practice emphasises the importance of re-evaluating instrument properties in individual research studies, our findings support the validity and applicability of the CarerQol instrument in a variety of settings. Due to minor differential reporting, pooling CarerQol data collected using mixed administration modes should be interpreted with caution; for TOPICS-MDS, meta-analytic techniques may be warranted.

A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.

Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.

[Reducing fragmentation in the care of frail older people: the successful development and implementation of the Health and Welfare Information Portal]. / Het verminderen van fragmentatie in de zorg voor kwetsbare ouderen: de succesvolle ontwikkeling en implementatie van het Zorg en WelzijnsInfoPortaal.

Our fragmented health care systems are insufficiently equipped to provide frail older people with high quality of care. Therefore, we developed the Health and Welfare Information Portal (ZWIP), an e-health intervention which aims (1) to facilitate self-management by frail older people and informal caregivers and (2) to improve collaboration among professionals. The ZWIP is a personal conference table, accessible through a secure internet connection, for multidisciplinary communication and information exchange for frail older people, their informal caregivers and professionals. After development, the ZWIP was implemented in seven general practices, and this process was evaluated by means of a mixed-methods study. Eventually, 290 frail older people and 169 professionals participated in the ZWIP. Most professionals were positive about its implementation. Facilitators for the implementation were the experienced need for improvement of interprofessional collaboration and the user-friendliness of the ZWIP. Barriers were the low computer-literacy of frail older people, start-up problems, preferring personal contact, and limited use of the ZWIP by other professionals. In sum, this article describes the successful development and implementation of the ZWIP, an e-health intervention which can reduce fragmentation in the care of frail older people.

Preoperative physical performance as predictor of postoperative outcomes in patients aged 65 and older scheduled for major abdominal cancer surgery: A systematic review.

BACKGROUND: Abdominal cancer surgery is associated with considerable morbidity in older patients. Assessment of preoperative physical status is therefore essential. The aim of this review was to describe and compare the objective physical tests that are currently used in abdominal cancer surgery in the older patient population with regard to postoperative outcomes. METHODS: Medline, Embase, CINAHL and Web of Science were searched until 31 December 2020. Non-interventional cohort studies were eligible if they included patients ≥65 years undergoing abdominal cancer surgery, reported results on objective preoperative physical assessment such as Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle strength, and on postoperative outcomes. RESULTS: 23 publications were included (10 CPET, 13 non-CPET including Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental shuttle walk test (ISWT)). Meta-analysis was precluded due to heterogeneity between study cohorts, different cut-off points, and inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic threshold and minute ventilation/carbon dioxide production gradient were associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two studies. Tests addressing muscle strength and function were of limited value. No study compared different physical tests. DISCUSSION: CPET has the ability to predict adverse postoperative outcomes, but it is time-consuming and requires expert assessment. ISWT or 6MWT might be a feasible alternative to estimate aerobic capacity. Muscle strength and function tests currently have limited value in risk prediction. Future research should compare the predictive value of different physical instruments with regard to postoperative outcomes in older surgical patients.

Cost-effectiveness of post-diagnosis treatment in dementia coordinated by Multidisciplinary Memory Clinics in comparison to treatment coordinated by general practitioners: an example of a pragmatic trial.

BACKGROUND: With the rising number of dementia patients with associated costs and the recognition that there is room for improvement in the provision of dementia care, the question arises on how to efficiently provide high quality dementia care. OBJECTIVE: To describe the design of a study to determine multidisciplinary memory clinics' (MMC) effectiveness and cost-effectiveness in post-diagnosis treatment and care-coordination of dementia patients and their caregivers compared to the post-diagnosis treatment and care-coordination by general practitioners (GP). Next, this article provides the theoretical background of pragmatic trials, often needed in complex interventions, with the AD- Euro study as an example of such a pragmatic approach in a clinical trial. METHOD: The study is a pragmatic multicentre, randomised clinical trial with an economic evaluation alongside, which aims to recruit 220 independently living patients with a new dementia diagnosis and their informal caregivers. After baseline measurements, patient and caregiver are allocated to the treatment arm MMC or GP and are visited for follow up measurements at 6 and 12 months. Primary outcome measures are Health Related Quality of Life of the patient as rated by the caregiver using the Quality of Life in Alzheimer's Disease instrument (Qol-AD) and self-perceived caregiving burden of the informal caregiver measured using the Sense of Competence Questionnaire (SCQ). To establish cost-effectiveness a cost-utility analysis using utilities generated by the EuroQol instrument (EQ-5D) will be conducted from a societal perspective. Analyses will be done in an intention-to-treat fashion. RESULTS: The inclusion period started in January 2008 and will commence until at least December 2008. After finalising follow up the results of the study are expected to be available halfway through 2010. DISCUSSION: The study will provide an answer to whether follow-up of dementia patients can best be done in specialised outpatient memory clinics or in primary care settings with regard to quality and costs. It will enable decision making on how to provide good and efficient health care services in dementia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00554047.

Liver proteome dataset of Sparus aurata exposed to low temperatures.

We report the proteomic dataset of livers from Sparus aurata exposed to low temperature during growth. Gilthead sea bream juveniles were reared in Recirculating Aquaculture Systems (RAS) and exposed to a temperature ramp made of two phases of four weeks each: a Cooling phase from 18 °C (t0) to 11 °C (t1) and a Cold Maintenance phase at 11 °C (t1-t2) in a 8 week feeding trial. At the end of the experiment, sea bream livers were collected and analyzed with a shotgun proteomics approach based on filter-aided sample preparation followed by tandem mass spectrometry, peptide identification carried out using Sequest-HT as search engine within the Proteome Discoverer informatic platform, and label-free differential analysis. The mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD011059 (Vizcaíno et al., 2016; Deutsch et al., 2017; Perez-Riverol et al., 2016). The dataset described here is also related to the research article entitled "Liver proteomics of gilthead sea bream (Sparus aurata) exposed to cold stress" (Ghisaura et al., 2019).

An in-home geriatric programme for vulnerable community-dwelling older people improves the detection of dementia in primary care.

BACKGROUND/OBJECTIVE: Dementia is under-diagnosed in primary care. This study investigated whether an in-home geriatric assessment and management programme could improve the identification of patients with dementia in primary care. METHODS: A secondary analysis was performed, using data of a randomised controlled trial that studied the effects of an in-home geriatric evaluation and management programme compared with usual care. In this trial, 151 vulnerable community-dwelling patients, aged 70 years and older, participated: 86 in the intervention group and 66 in de control group. The effect of the programme on the dementia detection rate was determined by comparing the number of new dementia diagnoses in both study arms at 6 months follow-up. RESULTS: Of all 151 participants, 38 (25%) had a registered dementia diagnosis at baseline. During follow-up, 23 of 113 patients without a registered dementia diagnosis at baseline were identified as suffering from dementia. The difference between the numbers of new dementia diagnoses in the intervention group (19 of 66 patients) and the control group (4 of 47 patients) was significant. (p = 0.02) CONCLUSION: An in-home geriatric assessment and management programme for vulnerable older patients improves the detection of dementia and can therefore contribute to overcoming of under-diagnosis of dementia.

Single versus multicomponent intervention in frail elderly: simplicity or complexity as precondition for success?

Research on geriatric syndromes has helped to clarify risk factors and established effective intervention strategies, yet the results based on this evidence have mostly failed to translate into clinical practice. The translation of geriatric syndrome research into practice faces unique challenges, which may heighten the barriers to evidence-based implementation. The British Medical Research Council framework (MRC) for development and evaluation of complex interventions, turns out to be very valuable in developing and evaluating interventions in the complex clinical reality of geriatrics. This paper illustrates the different phases of this framework on the basis of examples from geriatric research projects in The Netherlands. The discussed barriers in complex interventions can be mapped using the different phases in the MRC-framework and thus become feasible challenges for good quality research.

The ICTUS Study: A Prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort.

The long-term objective of the ICTUS study is to identify milestones in Alzheimer's disease (AD) progression and to develop a model to predict disease course in individual AD patients in Europe. The secondary objectives are to describe the patterns of prescribing, and the socioeconomic impact of AD in Europe. Between 2003 and 2005 1,380 patients with probable AD were recruited in specialised (secondary care) clinics in 12 European countries. Their mean age was 76 years and they had a mean of 8.0 +/- (SD) 4.6 years of education. Thirty-five percent were male. The mean MMSE score was 20.4 +/- (SD) 4.0. Forty-three percent had very mild dementia (CDR 0.5) and 44% had mild dementia (CDR 1). All patients completed baseline evaluation and biannual follow-up is ongoing. The goals of the current study are to describe the specific methods for recruitment in this crosscultural setting and the characteristics of the inception ICTUS cohort, including clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment and social burden.

[Dementia: growing disaster or declining epidemic?] / Dementie: groeiende ramp of afnemende epidemie?

- There is currently a lot of uncertainty about the future prevalence of dementia. Not only increasing age, but also educational level and lifestyle of the population appear to play a role.- There is little scientific and societal attention for the great uncertainty around average incidence and prevalence estimates for dementia.- When estimating the prognosis of people with dementia, the average disease course is often used as a basis, while this is not at all representative of the individual course of most patients.- The beneficial findings of recent lifestyle intervention studies ask for more targeted prevention strategies for risk groups. There is no standard preventative strategy which works equally well for everyone.- Given the large influence of dementia-related publications on the expectations of people regarding their ageing, it is important to present measures of dispersion alongside all study results.

Holocene sea ice variability driven by wind and polynya efficiency in the Ross Sea.

The causes of the recent increase in Antarctic sea ice extent, characterised by large regional contrasts and decadal variations, remain unclear. In the Ross Sea, where such a sea ice increase is reported, 50% of the sea ice is produced within wind-sustained latent-heat polynyas. Combining information from marine diatom records and sea salt sodium and water isotope ice core records, we here document contrasting patterns in sea ice variations between coastal and open sea areas in Western Ross Sea over the current interglacial period. Since about 3600 years before present, an increase in the efficiency of regional latent-heat polynyas resulted in more coastal sea ice, while sea ice extent decreased overall. These past changes coincide with remarkable optima or minima in the abundances of penguins, silverfish and seal remains, confirming the high sensitivity of marine ecosystems to environmental and especially coastal sea ice conditions.

Pseudo cluster randomization dealt with selection bias and contamination in clinical trials.

BACKGROUND AND OBJECTIVES: When contamination is present, randomization on a patient level leads to dilution of the treatment effect. The usual solution is to randomize on a cluster level, but at the cost of efficiency and more importantly, this may introduce selection bias. Furthermore, it may slow down recruitment in the clusters that are randomized to the "less interesting" treatment. We discuss an alternative randomization procedure to approach these problems. METHODS: Pseudo cluster randomization is a two-stage randomization procedure that balances between individual randomization and cluster randomization. For common scenarios, the design factors needed to calculate the appropriate sample size are tabulated. RESULTS: A pseudo cluster randomized design can reduce selection bias and contamination, while maintaining good efficiency and possibly improving enrollment. To make a well-informed choice of randomization procedure, we discuss the advantages of each method and provide a decision flow chart. CONCLUSION: When contamination is thought to be substantial in an individually randomized setting and a cluster randomized design would suffer from selection bias and/or slow recruitment, pseudo cluster randomization can be considered.

[The handling of acute life-threatening choking in geriatric and nursing home patients]. / De handelwijze bij acute levensbedreigende verstikking bij geriatrische en verpleeghuispatiënten.

It is unknown how often choking occurs in geriatric wards and in nursing homes and what the treatment and outcomes are in regular practice. A questionnaire was sent to Dutch geriatricians (N = 130), nursing home physicians (N = 130), and trainees for these disciplines (N = 215), in order to gain information about the experience, practice and competence of physicians in choking in geriatric and nursing home patients. We also analysed to what extent geriatric and nursing home wards were prepared for accurate handling of choking. The response rate was 30%. More than half of the responders had experienced an episode of food choking at least once in the past five years. The mortality rate in the reported cases was high (30%). The majority of the patients who died of choking had not received the Heimlich-manoeuvre. Physicians who had attended resuscitation training long ago felt as competent to manage a choking episode as physicians that had recently attended resuscitation training. Of all geriatric wards and nursing homes, the majority lacked a guideline on how to handle in acute food choking. Geriatric wards and nursing homes do not seem to be well prepared for acute food choking in several aspects. Despite methodological shortcomings of this study, the results underline the necessity of clarification of the terms used, and development and implementation of guidelines for this important problem.

Regions flanking ori sequences affect the replication efficiency of the mitochondrial genome of ori+ petite mutants from yeast.

The mitochondrial genomes of progenies from 26 crosses between 17 cytoplasmic, spontaneous, suppressive, ori+ petite mutants of Saccharomyces cerevisiae have been studied by electrophoresis of restriction fragments. Only parental genomes (or occasionally, genomes derived from them by secondary excisions) were found in the progenies of the almost 500 diploids investigated; no evidence for illegitimate, site-specific mitochondrial recombination was detected. One of the parental genomes was always found to be predominate over the other one, although to different extents in different crosses. This predominance appears to be due to a higher replication efficiency, which is correlated with a greater density of ori sequences on the mitochondrial genome (and with a shorter repeat unit size of the latter). Exceptions to the 'repeat-unit-size rule' were found, however, even when the parental mitochondrial genomes carried the same ori sequence. This indicates that noncoding, intergenic sequences outside ori sequences also play a role in modulating replication efficiency. Since in different petites such sequences differ in primary structure, size, and position relative to ori sequences, this modulation is likely to take place through an indirect effect on DNA and nucleoid structure.

Large-scale methylation patterns in the nuclear genomes of plants.

Methylation was investigated in compositional fractions of nuclear DNA preparations (50-100 kb in size) from five plants (onion, maize, rye, pea and tobacco), and was found to increase from GC-poor to GC-rich fractions. This methylation gradient showed different patterns in different plants and appears, therefore, to represent a novel, characteristic genome feature which concerns the noncoding, intergenic sequences that make up the bulk of the plant genomes investigated and mainly consist of repetitive sequences. The structural and functional implications of these results are discussed.

Tuberization in Cassava (Manihot esculenta): Cytokinin and Abscisic Acid Activity in Tuberous Roots.

The nature and distribution of cytokinins and abscisic acid in tuberous roots of cassava (Manihot esculenta Crantz) was studied. Trans-ribosylzeatin, dihydrozeatin and trans-zeatin were tentatively identified as the major cytokinins in tuberous root extracts. Cytokinin activity was concentrated in the meristematic region of the secondary xylem and in the phloem. This suggests a role for cytokinins in the regulation of meristematic activity which is responsible for the growth of the tuberous roots. Some cytokinin activity which co-eluted with cytokinin glucosides was found in extracts from the phloem. Inhibitor activity which was tentatively identified as cis-abscisic acid was present in tuberous root extracts. The activity of this hormone did not vary greatly between the different tissues analysed.

Antagonism between Yersinia intermedia and Yersinia enterocolitica in water.

One strain of Yersinia enterocolitica and one strain of Y. intermedia were grown in peptone water at 25 or 37 degrees C, or in ground water at 15 degrees C. Similar growth rates were observed when these strains were cultivated separately in the same media and at the same temperature. Mixed cultures at 37 degrees C displayed equivalent growth rates. In contrast, mixed cultures incubated at 15 or 25 degrees C were regularly unfavourable to Y. enterocolitica, whereas they did not modify the growth of Y. intermedia. A bacteriophage active on Y. enterocolitica and not on Y. intermedia was characterized from the filtrate of mixed cultures at low temperatures. This phage produced by the lysogenic Y. intermedia strain might be a potential factor responsible for the inhibition of Y. enterocolitica, since no additional antibacterial factor or nutritional competition between Y. intermedia and Y. enterocolitica were found in the mixed cultures.