A Non-Controlled Study of a Multi-Factorial Exercise and Nutritional Intervention to Improve Functional Performance and Prevent Frailty Progression in Community-Dwelling Pre-Frail Older Adults.

Background: Preventing frailty is important to avoid adverse health outcomes. Intervention studies have largely focused on frail elderly, although the intermediate pre-frail state may be more amenable to improvement. Objectives: This study aims to assess how physical performance may change among pre-frail elderly enrolled in a pragmatic non-controlled exercise and nutritional intervention programme. Methods: This is a non-controlled study involving a 4-month exercise and nutritional intervention for community dwelling pre-frail older adults. Pre-frailty was defined as the presence of 1 or 2 positive responses on the FRAIL questionnaire, or evidence of weak grip strength (<26kg for males; <18kg for females) or slow gait speed (<0.8m/s) amongst participants who were asymptomatic on FRAIL. Physical performance in flexibility, grip and lower limb strength, endurance, balance, and Short Physical Performance Battery were measured at 3 time-points: baseline, 3-month from recruitment (without intervention), and immediate post-intervention. Repeated measures mixed model analysis was performed to compare physical performance measures across the 3 time-points. Results: 94 pre-frail participants were eligible for intervention, of whom 59 (mean age = 70.9±7.2 years) were ready for the post-intervention review. 21 (35.6%) transitioned to robust phenotype while 32 (54.2%) remained as pre-frail. Significant improvement post-intervention was observed in lower limb strength and power, evident on reduction in time taken for 5 sit-to-stand repetitions (0.46±0.20s, p=0.03). There was no significant change to the other physical performance measures examined. Conclusion: We observed reversibility of pre-frailty, and the benefit of multi-component intervention in improving physical performance of pre-frail older adults. The findings in this non-controlled study will need to be corroborated with future controlled trials.

Frailty Assessment in Community-Dwelling Older Adults: A Comparison of 3 Diagnostic Instruments.

OBJECTIVES: Compare the diagnostic performance of FRAIL against Fried Phenotype and Frailty Index (FI), and identify clinical factors associated with pre-frailty/frailty. DESIGN: Cross-sectional analysis. SETTING: Community-based screenings in Senior Activity Centres, Residents' Corners and Community Centres in northeast Singapore. PARTICIPANTS: 517 community dwelling participants aged >55 years and ambulant independently (with/ without walking aids) were included in this study. Residents of sheltered or nursing homes, and seniors unable to ambulate at least four meters independently were excluded. MEASUREMENTS: The multidomain geriatric screen included assessments for social vulnerability, mood, cognition, sarcopenia and nutrition. Participants completed a battery of physical fitness tests for grip strength, gait speed, lower limb strength and power, flexibility, balance and endurance, with overall physical performance represented by Short Physical Performance Battery (SPPB). Frailty status was assigned on FRAIL, Fried and 35-item FI. RESULTS: Prevalence of frailty was 1.3% (FRAIL) to 3.1% (FI). Pre-frailty prevalence ranged from 17.0% (FRAIL) to 51.2% (FI). FRAIL demonstrated poor agreement with FI (kappa=0.171, p<0.0001), and Fried (kappa=0.194, p<0.0001). A lower FRAIL cut-off ≥1 yielded significantly improved AUC of 0.70 (95%CI 0.55 to 0.86, p=0.009) against Fried, and 0.71 (95%CI 0.55 to 0.86, p=0.008) against FI. All 3 frailty measures were diagnostic of impaired physical performance on SPPB, with AUCs ranging from 0.69 on FRAIL to 0.77 on Fried (all p values <0.01). Prevalence of low socio-economic status, depression, malnutrition and sarcopenia increased significantly, while fitness measures of gait speed, balance, and endurance declined progressively across robust, pre-frail and frail on all 3 frailty instruments (p <0.05). CONCLUSIONS: Our results suggest that different frailty instruments may capture over-lapping albeit distinct constructs, and thus may not be used interchangeably. FRAIL has utility for quick screening, and any positive response should trigger further assessment, including evaluation for depression, social vulnerability and malnutrition.

Identification of the novel HLA-B*39:01:01:04 allele in a Chinese individual by sequence-based typing.

The new HLA-B*39:01:01:04 allele differs from HLA-B*39:01:01 by a C → T substitution in intron 1.

Identification of a novel HLA-A*02:06:01:02 allele in a Chinese individual by sequence-based typing.

The new HLA-A*02:06:01:02 allele differs from HLA-A*02:06:01 by a C→G substitution in Intron 1.

The role of Schizosaccharomyces pombe SUMO ligases in genome stability.

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins.

The telomere-binding protein Taz1p as a target for modification by a SUMO-1 homologue in fission yeast.

In fission yeast (Schizosaccharomyces pombe) the homologue of the mammalian SUMO-1 ubiquitin-like modifier is encoded by the pmt3 gene. A two-hybrid screen using the telomere-binding protein Taz1p as bait identified Pmt3p as an interacting factor. In vitro experiments using purified components of the fission yeast Pmt3p modification system demonstrated that Taz1p could be modified directly by Pmt3p. The amino acid sequence of Taz1p contains a close match to the consensus modification site for SUMO-1, and a PEST sequence similar to those found in established SUMO-1 targets. Although previous experiments have identified an increase in telomere length as one consequence of the pmt3--genotype, we could not detect Pmt3p modification of Taz1p in protein extracts made from exponentially growing haploid cells or any effect of Pmt3p on the localization of GFP-Taz1p at discrete foci in the haploid cell nucleus.

Expression, purification and preliminary X-ray analysis of the BRCT domain from Rhp9/Crb2.

The BRCT domain from Rhp9 (a Schizosaccharomyces pombe DNA-damage checkpoint protein) has been expressed, purified and crystallized. Overexpression in bacterial cells was achieved by minimizing aeration during host cell growth. A robotic screen was used to determine the solubility parameters; concentration of the protein was achieved by exploiting this information. Single crystals suitable for X-ray analysis were obtained in two forms by vapour diffusion (trigonal, unit-cell parameters a = b = 228.04, c = 70.42 A, and tetragonal, P4/m Laue group symmetry, unit-cell parameters a = b = 72.3, c = 91.1 A).

A study of gut immunity to enteral endotoxin in rats of different ages: a possible cause for necrotizing enterocolitis.

PURPOSE: Immature gut immunity can be a predisposing factor for necrotizing enterocolitis (NEC). The gut active immunity and innate defense to the Escherichia coli endotoxin lipopolysaccharide (LPS) in immature and mature rats were studied. METHODS: LPS, started at a dose of 10 mg/kg, was instilled into the stomachs of fetal, newborn, 1-month and 3-month-old rats. Boost doses and normal saline control instillations were given on day 14. Rats that died after instillation had detailed postmortem examinations. For survivors, a group of 6 immunized and 6 controls were killed on day 7 for the collection of serum, spleens, mesenteric lymph nodes, and small intestines. Lymphocytes (10(6)) prepared from each tissue sample of individual group were cultured for 5 days. Serum and supernatant were analyzed for IgA and anti-E coli IgA levels. RESULTS: All control rats survived. The doses of LPS given were 10, 5, 2.5, and 1.25 mg/kg. All fetal rats died after LPS instillation. Half-lethal dose for newborns was 2.5 mg/kg. One-month and 3-month-old rats survived all doses of LPS. The cause of death was endotoxemia. The serum IgA and total supernatant anti- E coli IgA levels of rats of all ages studied showed no significant difference. CONCLUSION: The poor innate gut defense, not so much the active immunity, may provide an explanation for the susceptibility of the premature babies and newborn infants to the development of NEC.