Longitudinal changes in quality of life among elderly people with and without dementia.

ABSTRACTObjective:To study longitudinal changes in the quality of life (QoL) in persons with and without dementia, and explore the factors associated with baseline QoL and changes of QoL over the follow-up period. DESIGN: Prospective longitudinal study. SETTING: Data were collected from 17 municipalities in Norway in the period from January 2009 to August 2012. A total of 412 persons were included, 254 (61.7 %) persons without dementia and 158 (38.3 %) with dementia at baseline. SUBJECTS: Persons 70 years of age or older, receiving municipal care services. Main outcome measures include the following: self-rated and proxy-rated QoL over a period of 18 months, cognitive status, functional status, neuropsychiatric symptoms, and demographics. RESULTS: Longitudinal changes in QoL were small, despite changes in clinical variables. Proxy ratings of patients QoL were lower than the patients' own ratings. Belonging to a group with low QoL trajectory was associated with symptoms of depression, reduced physical and instrumental functioning, and more severe dementia. CONCLUSION: Patients and proxies evaluated the patients' QoL differently and QoL did not necessarily correspond with deterioration in clinical parameters. To prevent impaired QoL, we need to address identified factors and keep an approach open to the individual perceptions of QoL.

Change in psychotropic drug use in Norwegian nursing homes between 2004 and 2011.

ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed. METHODS: We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied. RESULTS: We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49-0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale. CONCLUSION: This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes.

The impact of dementia on the use of general practitioners among the elderly in Norway.

OBJECTIVE: To assess the use of general practitioners (GPs), in elderly home-dwelling persons in Norway and explore the impact of cognitive decline, age, and living situation. DESIGN: Prospective longitudinal study. SETTING: Data were collected from municipalities in four counties in Norway in the period from January 2009 to August 2012. SUBJECTS: Home-dwelling persons 70 years of age or older, receiving in-home care. MAIN OUTCOME MEASURES: Use of GPs over a period of 18 months related to cognitive state, functional status, neuropsychiatric symptoms, and demographics. RESULTS: A total of 599 persons were included. The mean annual number of consultations per participant was 5.6 (SD = 5.4). People with moderate to severe dementia had fewer consultations per year compared with those with mild or no dementia (3.7 versus 5.8 per year, p = 0.004). In the multivariate model higher age predicted fewer consultations while affective neuropsychiatric symptoms were associated with an increase in frequency of consultations. The most frequent reason to consult a GP was cardiovascular diseases (36.8% of all consultations), followed by musculoskeletal complaints (12.1%) and psychiatric diagnoses (8.7%). CONCLUSION: Our study shows that the home-dwelling elderly with moderate to severe dementia in Norway consult their GP less often than persons with mild or no dementia. This could indicate a need for better interaction between the municipal care and social services and the general practitioners.

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

The morphological evolution of galaxies.

Many galaxies have taken on their familiar appearance relatively recently. In the distant Universe, galaxy morphology deviates significantly (and systematically) from that of nearby galaxies at redshifts (z) as low as 0.3. This corresponds to a time approximately 3.5 x 10(9) years in the past, which is only approximately 25% of the present age of the Universe. Beyond z = 0.5 (5 x 10(9) years in the past), spiral arms are less well developed and more chaotic, and barred spiral galaxies may become rarer. At z = 1, around 30% of the galaxy population is sufficiently peculiar that classification on Hubble's traditional "tuning fork" system is meaningless. On the other hand, some characteristics of galaxies have not changed much over time. The space density of luminous disk galaxies has not changed significantly since z = 1, indicating that although the general appearance of these galaxies has continuously changed over time, their overall numbers have been conserved.

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

Gene arrangement and organization in a approximately 76 kb fragment encompassing the oriC region of the chromosome of Mycobacterium leprae.

A continuous 75627 bp segment of the Mycobacterium leprae chromosome spanning the oriC region was sequenced. The gene order at this locus was similar to that found in the replication origin region of many other prokaryotes, particularly Mycobacterium tuberculosis and Streptomyces coelicolor. As in the case of several Gram-positive bacteria, essential genes involved in basic cellular functions, such as DNA or RNA metabolism (dnaA, dnaB, dnaN, gyrB, gyrA, pcnB, recF, rnpA, ssb), cell wall synthesis (ponA, pbpA) and probably cell division (gidB, rodA) were found. Strikingly, the gidA gene was absent from this part of the genome and there was no rRNA operon near oriC. The gyrA gene harbours an intein coding sequence indicating that protein splicing is required to produce the mature A subunit of DNA gyrase. Among the many other noteworthy features were ORFs encoding putative serine/threonine protein kinases and a protein phosphatase, three tRNA genes, one M. leprae-specific repetitive element and a glnQ pseudogene.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis, was constructed by using a twin-pronged approach. Pulsed-field gel electrophoretic analysis enabled cleavage sites for Asn I and Dra I to be positioned on the 4.4-Mb circular chromosome, while, in parallel, clones from two cosmid libraries were ordered into contigs by means of fingerprinting and hybridization mapping. The resultant contig map was readily correlated with the physical map of the genome via the landmarked restriction sites. Over 165 genes and markers were localized on the integrated map, thus enabling comparisons with the leprosy bacillus, Mycobacterium leprae, to be undertaken. Mycobacterial genomes appear to have evolved as mosaic structures since extended segments with conserved gene order and organization are interspersed with different flanking regions. Repetitive sequences and insertion elements are highly abundant in M. tuberculosis, but the distribution of IS6110 is apparently nonrandom.

Galaxies, human eyes, and artificial neural networks.

The quantitative morphological classification of galaxies is important for understanding the origin of type frequency and correlations with environment. However, galaxy morphological classification is still mainly done visually by dedicated individuals, in the spirit of Hubble's original scheme and its modifications. The rapid increase in data on galaxy images at low and high redshift calls for a re-examination of the classification schemes and for automatic methods. Here are shown results from a systematic comparison of the dispersion among human experts classifying a uniformly selected sample of more than 800 digitized galaxy images. These galaxy images were then classified by six of the authors independently. The human classifications are compared with each other and with an automatic classification by an artificial neural network, which replicates the classification by a human expert to the same degree of agreement as that between two human experts.

MycDB: an integrated mycobacterial database.

As part of ongoing efforts to investigate the molecular biology of the human pathogens in the genus Mycobacterium, a customized database was developed specifically for these organisms and implemented in ACEDB database manager software. The data loaded include the IMMYC Antigen List, details of reagents available from the CDC/WHO Antibody Bank, more than 1 Mb of sequences of mycobacterial genes and proteins from public databases, the physical maps of Mycobacterium leprae and Mycobacterium tuberculosis developed at the Institut Pasteur, as well as a subset of the references found in MedLine. The ACEDB software allows both quick and intuitive access to the data and to connections between facts by a simple mouse-driven interface, as well as by more powerful query mechanisms.

Subunit structure of a class A aspartate transcarbamoylase from Pseudomonas fluorescens.

The class A aspartate transcarbamoylase (ATCase, EC 2.1.3.2) from Pseudomonas fluorescens was purified to homogeneity with retention of full catalytic and regulatory functions. Careful determinations under conditions that minimized proteolysis showed that the molecule is a 1:1 stoichiometric complex of two polypeptide chains of 34 and 45 kDa. Pyridoxal phosphate is a competitive inhibitor of the enzyme (Ki = 1 microM). Reduction of the pyridoxal phosphate enzyme adduct with sodium boro[3H]hydride showed that the active site is located on the 34-kDa polypeptide. Affinity labeling with 5'-[p-(fluorosulfonyl)benzoyl]adenosine, an ATP analog, suggested that the regulatory site is also located on the 34-kDa species. While the function of the 45-kDa subunit is unknown, neither carbamoyl phosphate synthetase nor dihydroorotase activities are associated with the ATCase. The molecular mass of the enzyme was determined by gel filtration, sedimentation velocity, and electron microscopy to be 464 kDa. Thus the enzyme is composed of six copies of the 34-kDa polypeptide and six copies of the 45-kDa polypeptide. The molecule has a Stokes' ratio of 70.9 A and a frictional ratio of 1.37, suggesting a compact globular shape. We propose that the P. fluorescens ATCase is composed of two trimers of 34-kDa catalytic chains and is likely to be a D3 dodecamer with an arrangement of subunits analogous to that of the class B ATCase molecules.

Is the velocity-distance relation for galaxies linear?

Diameters of ScI galaxies, the luminosities of supernovae of type Ia at maximum light, and the brightness of central galaxies in rich clusters are examined as potential yardsticks or standard candles for study of the velocity-distance relationship. Both supergiant ScI galaxies and supernovae Ia (which have luminosities that differ by up to a factor of approximately 10) are found to be unsuitable for such a study. The remarkably small luminosity dispersion of first-ranked cluster galaxies (which is not yet understood physically) suggests that deviations from a linear velocity-distance relationship are less, approximately 20% out to red shifts of approximately 40,000 km.s-1.

Nucleotide sequence of the first cosmid from the Mycobacterium leprae genome project: structure and function of the Rif-Str regions.

The nucleotide sequence of cosmid B1790, carrying the Rif-Str regions of the Mycobacterium leprae chromosome, has been determined. Twelve open reading frames were identified in the 36716bp sequence, representing 40% of the coding capacity. Five ribosomal proteins, two elongation factors and the beta and beta' subunits of RNA polymerase have been characterized and two novel genes were found. One of these encodes a member of the so-called ABC family of ATP-binding proteins while the other appears to encode an enzyme involved in repairing genomic lesions caused by free radicals. This finding may well be significant as M. leprae, an intracellular pathogen, lives within macrophages.

The facultative anaerobic energy metabolism of Schistosoma mansoni sporocysts.

Schistosoma mansoni miracidia in water are known to possess an aerobic energy metabolism, the Krebs cycle being the main terminal of the breakdown of endogenous glycogen reserves. The present study demonstrated that after in vitro transformation of miracidia into sporocysts, the organisms degraded glucose to lactate and carbon dioxide in a more anaerobic ratio than do miracidia. The occurrence of a large Pasteur effect demonstrated, however, that oxidative phosphorylation was still the major process used for energy generation. After 24 h in vitro cultivation the sporocysts had consumed more external glucose and their metabolism had shifted towards lactate production. Sporocysts could cope with inhibited respiration: they had a large anaerobic capacity and survived perfectly in the presence of cyanide, producing a large amount of succinate in addition to lactate. It was demonstrated that this succinate was largely produced via phosphoenolpyruvate carboxykinase (PEPCK). This pathway, which is known to occur in most parasitic helminths, has never been demonstrated in schistosomes, not even in the miracidial stage immediately preceding the sporocysts. It was also shown that in sporocysts part of the lactate was not formed directly by glycolysis, but via a detour including fumarate and the action of PEPCK. The results demonstrated that S. mansoni sporocysts are facultative anaerobes, fully equipped to adjust their energy metabolism to the variable conditions inside their intermediate host, the snail. In the presence of oxygen, they derive most of their energy from the aerobic degradation of glucose to carbon dioxide, but under anaerobic conditions they switch towards lactate and succinate production.

The age and size of the universe.

Modern distance determinations to galaxies were reviewed and placed on a uniform and self-consistent scale. Based on eight separate but not entirely independent techniques, the distance to the Virgo cluster was found to be 15.8 +/- 1.1 megaparsec. Twelve different determinations yield a Coma/Virgo distance ratio of 5.52 +/- 0.13 and hence a Coma distance of 87 +/- 6 megaparsec. With a cosmological redshift of 7210 kilometers per second, this gives a Hubble parameter H(0) (local) of 83 +/- 6 kilometers per second per megaparsec. From the velocity-distance relation of rich clusters of galaxies, the ratio of the value of H(0) (global) to the value of H(0) (local) was determined to be 0.92 +/- 0.08. In other words, the cluster data do not show a statistically significant difference between the local and global values of the Hubble parameter. If one nevertheless adopts this relation between H(0) (global) and H(0) (local), then the value of H(0) (global) is 76 +/- 9 kilometers per second per megaparsec. This observed value differs at the approximately 3sigma level (where sigma is the standard deviation of the distribution) from values in the range 36 less, similar H(0) less, similar50 kilometers per second per megaparsec, which are derived from stellar evolutionary theory in conjunction with standard cosmological models with a density parameter (Omega) that is equal to 1 and a cosmological constant (lambda) that is equal to 0.