[Review in geriatric medicine 2012]. / Gériatrie.

2012 brought additional evidence regarding the benefits of exercise in older persons in showing morbidity compression in those most active. Several studies invite to revise therapeutic targets in older diabetics, especially those with cognitive impairment or dementia where a value of 8 to 9% for HbAlc might be a good compromise. On the dementia side, a study suggests that biological and structural abnormalities associated with Alzheimer's disease might occur as early as 25 years before its first clinical manifestations. On the therapeutic side, ginkgo and the double therapy with memantine and donepezil did not make it in RCTs, and two studies about treatments for behavioral symptoms of dementia showed that interruption could be deleterious.

[Review in geriatric medicine 2011]. / Gériatrie.

In 2011, new tools to evaluate life expectancy are available. Controversy about PSA-based screening for prostate cancer is still going on, with new data from the US Preventive services task force. A brief behavioral treatment for insomnia can be efficient and durable. Gliptines are be useful to avoid treatment-induced hypoglycemia in diabetic patients. New Alzheimer diagnostic criteria, including biomarkers, have been published.

[HIV infection and the elderly]. / Infection VIH et personnes âgées.

HIV infection is becoming a chronic disease, due to decreased mortality induced by the introduction of combined antiviral treatments. The HIV positive population is aging progressively. HIV infection in the elderly has certain specificities, including a late initial diagnosis, a less marked immune response to treatment and the potential association of multiple comorbidities associated with HIV infection and aging. These factors may affect the quality of life of elderly patients and ultimately lead to increased functional dependence. Screening and specific treatment of comorbidities associated with HIV and aging are particularly recommended.

Multi-parametric evaluation of sit-to-stand and stand-to-sit transitions in elderly people.

The aim of this study was to extract multi-parametric measures characterizing different features of sit-to-stand (Si-St) and stand-to-sit (St-Si) transitions in older persons, using a single inertial sensor attached to the chest. Investigated parameters were transition's duration, range of trunk tilt, smoothness of transition pattern assessed by its fractal dimension, and trunk movement's dynamic described by local wavelet energy. A measurement protocol with a Si-St followed by a St-Si postural transition was performed by two groups of participants: the first group (N=79) included Frail Elderly subjects admitted to a post-acute rehabilitation facility and the second group (N=27) were healthy community-dwelling elderly persons. Subjects were also evaluated with Tinetti's POMA scale. Compared to Healthy Elderly persons, frail group at baseline had significantly longer Si-St (3.85±1.04 vs. 2.60±0.32, p=0.001) and St-Si (4.08±1.21 vs. 2.81±0.36, p=0.001) transition's duration. Frail older persons also had significantly decreased smoothness of Si-St transition pattern (1.36±0.07 vs. 1.21±0.05, p=0.001) and dynamic of trunk movement. Measurements after three weeks of rehabilitation in frail older persons showed that smoothness of transition pattern had the highest improvement effect size (0.4) and discriminative performance. These results demonstrate the potential interest of such parameters to distinguish older subjects with different functional and health conditions.

[Review in geriatric medicine]. / Gériatrie.

In 2010, a study emphasizes the difficulty to predict disability trajectories in the last year of life. A meta analysis shows the effectiveness of post-acute geriatric rehabilitation in reducing functional decline after hospitalisation. Several studies evaluated pneumococcal and herpes zoster vaccines' efficacy. A short and simple intervention is effective in reducing benzodiazepine use. The effect of vitamine D on falls and fractures has been further evaluated in several studies. Diagnostic criteria for dementias, including Alzheimer's disease, are moving to better acknowledge their preclinical stages.

Strategy for the identification of key odorants: application to shrimp aroma.

The GC-SNIF technique was used to obtain the olfactograms of shrimps, and their impact odorants were identified by MS hyphenated to the GC/olfactometric system and by comprehensive two-dimensional GC hyphenated to a time-of-flight MS. Confirming these identifications by their linear retention indices required application of a new strategy to compare retention indices between both instruments and with the in-house database. The aldehydes were confirmed by using their pentafluorophenylhydrazone derivatives, and 2-ethyl-3,5-dimethyl pyrazine had to be resolved from co-eluting compounds and then identified by multidimensional GC hyphenated to an MS and a sniff port. In both shrimp products, the most important odorants were trimethylamine, 2-acetyl-1-pyrroline, and 2-ethyl-3,5-dimethyl pyrazine, together with common carbonyl compounds.

[Assessment of gait disorders in older people]. / Evaluer les troubles de la marche des personnes âgées au cabinet.

Gait disorders are frequent and important to assess in older people because they provide unique diagnostic and prognostic information. Gait disorders can be regarded as a marker of frailty because they are associated with several adverse consequences, including falls, cognitive disorders, functional decline, institutionalization, hospitalization, and death. Using structured instruments, gait assessment could be performed in primary care practice to classify the level of sensorimotor deficit and provide the necessary information to decide how to best intervene to improve gait performances, prevent falls as well as functional decline.

Kinematics and dynamic complexity of postural transitions in frail elderly subjects.

The aim of this study was to propose a methodology allowing a detailed characterization of body sit-to-stand/stand-to-sit postural transition. Parameters characterizing the kinematics of the trunk movement during sit-to-stand (Si-St) postural transition were calculated using one initial sensor system fixed on the trunk and a data logger. Dynamic complexity of these postural transitions was estimated by fractal dimension of acceleration-angular velocity plot. We concluded that this method provides a simple and accurate tool for monitoring frail elderly and to objectively evaluate the efficacy of a rehabilitation program.

[Oral anticoagulation in elderly people]. / Anticoagulation orate chez les personnes âgées.

Oral anticoagulation in elderly people is a complex problem. The decision to initiate anticoagulant therapy in a patient with atrial fibrillation require to balance potential benefits (decreased risk of ischemic stroke) and risks (major hemorrhage, in particular intracranial), in the context of each patient's specific characteristics. Once the patient has been informed, his/her preferences must be integrated into the treatment decision-making process. Current guidelines recommend anticoagulation in all patients aged 75 years and more with atrial fibrillation who do not have counterindications to this treatment. Patients aged 65 to 75 years should also receive an anticoagulation, especially those with cardio-vascular risk factors.

CXCR3 internalization following T cell-endothelial cell contact: preferential role of IFN-inducible T cell alpha chemoattractant (CXCL11).

Chemokine receptors are rapidly desensitized and internalized following ligand binding, a process that attenuates receptor-mediated responses. However, the physiological settings in which this process occurs are not clear. Therefore, we examined the fate of CXCR3, a chemokine receptor preferentially expressed on activated T cells following contact with endothelial cells. By immunofluorescence microscopy and flow cytometry, we found that CXCR3 was rapidly internalized when T cells were incubated with IFN-gamma-activated human saphenous vein endothelial cells (HSVEC), but not with resting HSVEC. Similar results were obtained using human CXCR3-transfected murine 300-19 B cells. CXCR3 down-regulation was significantly more pronounced when T cells were in contact with HSVEC than with their supernatants, suggesting that CXCR3 ligands were efficiently displayed on the surface of HSVEC. Using neutralizing mAbs to IFN-induced protein-10 (CXCL10), monokine induced by IFN-gamma (CXCL9), and IFN-inducible T cell alpha chemoattractant (I-TAC; CXCL11), we found that even though I-TAC was secreted from IFN-gamma-activated HSVEC to lower levels than IFN-induced protein-10 or the monokine induced by IFN-gamma, it was the principal chemokine responsible for CXCR3 internalization. This correlated with studies using recombinant chemokines, which revealed that I-TAC was the most potent inducer of CXCR3 down-regulation and of transendothelial migration. Known inhibitors of chemokine-induced chemotaxis, such as pertussis toxin or wortmannin, did not reduce ligand-induced internalization, suggesting that a distinct signal transduction pathway mediates internalization. Our data demonstrate that I-TAC is the physiological inducer of CXCR3 internalization and suggest that chemokine receptor internalization occurs in physiological settings, such as leukocyte contact with an activated endothelium.

Downstream sequences influence the choice between a naturally occurring noncanonical and closely positioned upstream canonical heptameric fusion motif during bovine coronavirus subgenomic mRNA synthesis.

Mechanisms leading to subgenomic mRNA (sgmRNA) synthesis in coronaviruses are poorly understood but are known to involve a heptameric signaling motif, originally called the intergenic sequence. The intergenic sequence is the presumed crossover region (fusion site) for RNA-dependent RNA polymerase (RdRp) during discontinuous transcription, a process leading to sgmRNAs that are both 5' and 3' coterminal. In the bovine coronavirus, the major fusion site for synthesis of mRNA 5 (GGUAGAC) does not conform to the canonical motif (UC[U,C]AAAC) at three positions (underlined), yet it lies just 14 nucleotides downstream from such a sequence (UCCAAAC). The infrequently used canonical sequence, by computer prediction, is buried within the stem of a stable hairpin (-17.2 kcal/mol). Here we document the existence of this stem by enzyme probing and examine its influence and that of neighboring sequences on the unusual choice of fusion sites by analyzing transcripts made in vivo from mutated defective interfering RNA constructs. We learned that (i) mutations that were predicted to unfold the stem-loop in various ways did not switch RdRp crossover to the upstream canonical site, (ii) a totally nonconforming downstream motif resulted in no measurable transcription from either site, (iii) the canonical upstream site does not function ectopically to lend competence to the downstream noncanonical site, and (iv) altering flanking sequences downstream of the downstream noncanonical motif in ways that diminish sequence similarity with the virus genome 5' end caused a dramatic switch to the upstream canonical site. These results show that sequence elements downstream of the noncanonical site can dramatically influence the choice of fusion sites for synthesis of mRNA 5 and are interpreted as being most consistent with a mechanism of similarity-assisted RdRp strand switching during minus-strand synthesis.

Individual identification of cats and dogs using mitochondrial DNA tandem repeats?

Cats and dogs are very common animals in the human environment. In Switzerland, one in five households owns a cat or a dog. Their hairs are very easily transferred and could be used as a frequent trace evidence. Using DNA analysis, identification of these animals should be possible as it is in human identification. However, most of the time, no nuclear DNA can be recovered from the hair. It is therefore necessary to rely on mtDNA. Cats and dogs have tandemly repeated sequences in their mtDNA control region. In this study, the authors show that these tandem repeats are very polymorphic but are also the source of a very high level of heteroplasmy. The authors, therefore, examined if this might prevent their use in forensic identification.

The hypervariable C-terminal tail of the Sendai paramyxovirus nucleocapsid protein is required for template function but not for RNA encapsidation.

The paramyxovirus nucleocapsid proteins (NPs) are relatively well conserved, except for the C-terminal 20% (or ca. 100 amino acids), referred to as the tail. We have examined whether this hypervariable tail is required for genome synthesis, both in vitro, where synthesis is predominantly from the input templates, and in vivo, where multiple rounds of amplification occur. In these viruses, genome synthesis and assembly of the nascent chain are coupled. We find that the tail is required in vivo but not in vitro. Closer examination of the in vivo system showed that the tailless NP could encapsidate the genome chain but that amplification did not occur. We interpret these results as indicating that the tail is not required for RNA assembly but is required for the template to function in RNA synthesis. Relatively small deletions within the conserved N-terminal 80% of the protein, on the other hand, rendered the protein nonfunctional in either system. The possible functions of the tail in RNA synthesis are discussed.

The Tacaribe arenavirus small zinc finger protein is required for both mRNA synthesis and genome replication.

An antiserum to a peptide of the Tacaribe virus Z protein was used to determine whether this small Zn(2+)-binding protein was required for viral RNA synthesis in infected cell extracts. Specific immunodepletion of the extracts invariably reduced genome synthesis to near background levels, but strong effects on mRNA synthesis occurred only early in the infection or when mRNA synthesis was relatively weak. Our results suggest that the Z protein is required for both mRNA and genome synthesis, but in somewhat different manners.

Loss of V protein expression in human parainfluenza virus type 1 is not a recent event.

The P gene of paramyxoviruses usually contains an alternate overlapping ORF coding for a short cysteine-rich domain called V. This domain was thought to be a common feature of these genes as it is present in ten paramyxoviruses. However, the V ORF region of the P gene of one strain of human parainfluenza-virus type 1 (isolated in 1957) was recently found to be closed by no less than 9 stop codons. To determine whether the absence of the V ORF here might be due to the long adaptation of this strain in culture, 3 other more recent isolates were examined. Small differences in the V region were found, but all had conserved the vast majority of the stop codons. Moreover, examination of most of the intercistronic regions of the PIV1 genome failed to uncover a cryptic V gene. The V ORF is then unlikely to be a common feature of paramyxovirus P genes.

Strict distance requirement for transcriptional activation by two regulatory elements of the glucagon gene.

The glucagon gene is specifically expressed in A cells of the pancreatic islets. We have previously identified three functional DNA control elements within the 5'-flanking sequence of the glucagon gene: an upstream promoter element (G1), responsible for the A-cell-specific expression, and two enhancer-like elements (G2 and G3). Mutations within G1 completely abolished the enhancer activities of G2 and G3. We show here that the loss of transcriptional activity is not due to an absence of binding of nuclear proteins to G2 or G3, but rather to an essential role of G1 to enable G2 and G3 to exert their effects at a distance. When juxtaposed to the TATA box, both enhancers are capable of inducing transcription as efficiently as when an intact G1 is present. However, the tandem arrangement of G2 plus G3 does not result in additional transcriptional activity compared with a single element. We conclude that G2 and G3 are capable of directly activating transcription but in a highly distance-dependent fashion and without cooperatively interacting. G1 may thus serve only as a tissue-specific relay, bringing together factors that bind to enhancers and the TATA box.

Anti-mRNAs in La Crosse bunyavirus-infected cells.

Unlike some members of the family Bunyaviridae which contain ambisense genomes, all La Crosse virus reading frames are translated from antigenome sense mRNAs. Nevertheless, La Crosse virus genome sense mRNAs or anti-mRNAs are initiated from antigenome templates. These are characterized by the same range of capped, nontemplated sequences at their 5' ends as mRNAs, but their 3' ends are presumed to be heterogenous, as they were not seen on RNA blots. The anti-mRNAs are estimated to be 15 to 30 times less abundant than mRNAs, but remarkably, this ratio is similar to that of functional genome sense mRNAs made from other bona fide ambisense segments. A role for these anti-mRNAs during infection is unclear.