Screening for frailty in community-dwelling elderly subjects: Predictive validity of the modified SEGA instrument.

AIMS: To study the capacity of the SEGAm instrument to predict loss of independence among elderly community-dwelling subjects. METHODS: The study was performed in four French departments (Ardennes, Marne, Meurthe-et-Moselle, Meuse). Subjects aged 65 years or more, living at home, who could read and understand French, with a degree of autonomy corresponding to groups 5 or 6 in the AGGIR autonomy evaluation scale were included. Assessment included demographic characteristics, comprehensive geriatric assessment, and the SEGAm instrument at baseline. Subjects had follow-up visits at home at 6 and 12 months. During follow-up, vital status and level of independence were recorded. Logistic regression was used to study predictive validity of the SEGAm instrument. RESULTS: Among the 116 subjects with complete follow-up, 84 (72.4%) were classed as not very frail at baseline, 23 (19.8%) as frail, and 9 (7.8%) as very frail; 63 (54.3%) suffered loss of at least one ADL or IADL at 12 months. By multivariable analysis, frailty status at baseline was significantly associated with loss of independence during the 12 months of follow-up (OR=4.52, 95% CI=1.40-14.68; p=0.01). We previously validated the SEGAm instrument in terms of feasibility, acceptability, internal structure validity, reliability, and discriminant validity. CONCLUSIONS: This instrument appears to be a suitable tool for screening frailty among community-dwelling elderly subjects, and could be used as a basis to plan early targeted interventions for subjects at risk of adverse outcome.

Screening for frailty in elderly subjects living at home: validation of the Modified Short Emergency Geriatric Assessment (SEGAm) instrument.

OBJECTIVES: To validate the modified version of the Short Emergency Geriatric Assessment (SEGAm) frailty instrument in elderly people living at home. DESIGN: Longitudinal, prospective, multicentre study. SETTING: Four departments (Ardennes, Marne, Meurthe-et-Moselle, Meuse) in two French Regions (Champagne-Ardenne and Lorraine). PARTICIPANTS: Subjects aged 65 years or more, living at home, who could read and understand French, with a degree of autonomy corresponding to groups 5, or 6 in the AGGIR autonomy evaluation scale. MEASUREMENTS: Assessment included demographic characteristics, comprehensive geriatric assessment, and the SEGAm instrument. Psychometric validation was used to study feasibility and acceptability, internal structure validity, reliability, and discriminant validity of the SEGAm instrument. RESULTS: Between July 1st 2012 and March 31st 2013, 167 patients were included in the study. Averaged age was 77±7 years, the majority were women (70.7%). Feasibility and acceptability of the SEGAm instrument were excellent: we observed no refusal to participate, no drop-out during administration, no missing items, no ceiling or floor effects, and the administration time was short (5.0±3.5 min). By factor analysis, the instrument proved to be unidimensional. It showed good internal consistency (Cronbach's alpha coefficient: 0.68) and good test-retest (intra-class correlation: 0.88) at 7 days interval. Discriminant validity showed a significant difference, mainly for nutritional status, fall risk, dependency, mood and depression risk, and comorbidities. CONCLUSION: Based on these psychometric properties, the SEGAm appears to be an easy-to-use instrument that is particularly suitable for use in the community to identify frail elderly people who could benefit from early targeted interventions.

Turnera ulmifolia L. (Turneraceae): preliminary study of its antioxidant activity.

Turnera ulmifolia L. is used in Brazilian folk medicine as an anti-inflammatory. Since this activity may be correlated with the presence of antioxidant compounds, a leaf extract was evaluated for its radical scavenging capacity (RSC). The in vitro RSC of a 50% hydroethanolic (HE) extract was evaluated by beta-carotene/linoleic acid coupled oxidation system for the inhibition of oxidation and the lipid peroxidation inhibition in rat brain homogenates, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence (CL). Results indicated, through peroxidation suppression, that this extract exhibited greater antioxidative activity (77.4% +/- 10%) than alpha-tocopherol (58.4% +/- 3.7%). TBARS and CL inhibition was concentration-dependent and Q(1/2) values were 8.2 and 6.0 microg/mL for TBARS and CL, respectively. For alpha-tocopherol these values were 7.1 microg/mL (TBARS) and 9.8 microg/mL (CL). Phenolic compounds may be responsible for this antioxidant capacity.

A two-dimensional 1H-NMR study of the dam methylase site: comparison between the hemimethylated GATC sequence, its unmethylated analogue and a hemimethylated CATG sequence. The sequence dependence of methylation upon base-pair lifetimes.

We report two-dimensional NOE (NOESY) spectra on the sequence d(GCGATCATGG).d(CCATGATCGC) which contains the unmethylated dam site. As expected the DNA adopts a B-form conformation but appears to be distorted at the TG step of the second strand. This distorsion, probably bending, is not seen on the opposite strand. When the first strand is methylated on adenine in the GATC or CATG sequence the NOESY spectra indicate little or no change in the conformation. However the single strand-duplex exchange is slowed down to the slow-exchange region on a proton NMR time scale. We have assigned the exchangeable imino and cytidine amino resonances of the three duplexes. From the imino linewidths as a function of temperature, we observe that the unmethylated and the hemimethylated Gm6ATC duplexes melt normally from the ends. However, this is not so for the hemimethylated Cm6ATG duplex which, apart from the terminal base pairs, melts cooperatively and at higher temperature. In spectra recorded in H2O a second duplex is observed, for the Gm6ATC sequence, which we have not been able to identify. It is however unlikely to be a hairpin structure. Ultraviolet-melting curves also indicate the presence of two transitions for this duplex. The effect of methylation upon base-pair lifetimes has been studied by comparing the above three duplexes. Little effect is observed upon methylation in the GATC sequence but a drastic increase in the lifetimes of all base pairs is observed upon methylation in the CATG sequence.

Comparison of the conformation of an oligonucleotide containing a central G-T base pair with the non-mismatch sequence by proton NMR.

We have recorded NOESY spectra of two non-selfcomplementary undecanucleotide duplexes. From the observed NOEs we do not detect any significant distortion of the helix when a G-C pair is replaced by a G-T pair and the normal interresidue connectivities can be followed through the mismatch site. We conclude that the 2D spectra of the non-exchangeable protons do not allow differentiation between a wobble or rare tautomer form for the mismatch. NOE measurements in H2O, however, clearly show that the mismatch adopts a wobble structure and give information on the hydration in the minor groove for the G-T base pair which is embedded between two A-T base pairs in the sequence.

Structures of mismatched base pairs in DNA and their recognition by the Escherichia coli mismatch repair system.

The Escherichia coli mismatch repair system does not recognize and/or repair all mismatched base pairs with equal efficiency: whereas transition mismatches (G X T and A X C) are well repaired, the repair of some transversion mismatches (e.g. A X G or C X T) appears to depend on their position in heteroduplex DNA of phage lambda. Undecamers were synthesized and annealed to form heteroduplexes with a single base-pair mismatch in the centre and with the five base pairs flanking each side corresponding to either repaired or unrepaired heteroduplexes of lambda DNA. Nuclear magnetic resonance (n.m.r.) studies show that a G X A mismatch gives rise to an equilibrium between fully helical and a looped-out structure. In the unrepaired G X A mismatch duplex the latter predominates, while the helical structure is predominant in the case of repaired G X A and G X T mismatches. It appears that the E. coli mismatch repair enzymes recognize and repair intrahelical mismatched bases, but not the extrahelical bases in the looped-out structures.

An NMR study of A-T base pair opening rates in oligonucleotides. Influence of sequence and of adenine methylation.

We report relaxation time measurements by semi-selective and totally selective NMR techniques on the thymidine imino protons of d(GGATATCC) and d(GGm6ATATCC). For these oligonucleotides helix fraying, rather than single base pair opening, is the major exchange mechanism even 25 degrees C below the Tm. We have therefore applied a new saturation transfer technique to measure exchange rates at temperatures where fraying has a very small or negligible contribution. Measurements of exchange rates as a function of temperature give significantly different activation energies for base pairs 3 and 4 in d(GGATATCC). Adenine methylation results in a slowing down of the opening rate for the m6A-T base pair but surprisingly has an even greater effect upon the adjacent non-methylated A-T base pair.

Consequences of methylation on the amino group of adenine. A proton two-dimensional NMR study of d(GGATATCC) and d(GGm6ATATCC).

A two-dimensional 500-MHz 1H-NMR study of two oligonucleotides, d(GGATATCC) and d(GGm6ATATCC), is presented in which we have investigated the effects of adenine methylation. The two-dimensional nuclear Overhauser spectra (NOESY) show that both oligonucleotides adopt a normal right-handed B-type helix and one-dimensional nuclear Overhauser enhancement (NOE) studies demonstrate that any difference in conformation must be small. However methylation drastically slows down the helix in equilibrium coil exchange which becomes slow on a proton NMR time scale. While d(GGATATCC) fits a two-site exchange model, d(GGm6ATATCC) does not and we invoke the presence of a third species which may be an intermediate in helix formation. NMR and ultraviolet spectroscopy show that methylation destabilizes the helix, measured by the melting temperature and enthalpy of dissociation.

A proton 2D-NMR study of an oligodeoxyribonucleotide containing N6-methyladenine:d(GGm6ATATCC).

The presence of a m6A-T base pair does not give rise to a major change in helix conformation from that of a normal B DNA, but does slow down dramatically the rate of helix formation.