Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Is diabetes associated with poorer self-efficacy and motivation for physical activity in older adults with arthritis?

OBJECTIVES: The primary aim was to explore whether arthritis is associated with poorer self-efficacy and motivation for, and participation in, two specific types of physical activity (PA): endurance training (ET) and strength training (ST). A further objective was to determine whether the added burden of diabetes contributes to a further reduction in these PA determinants and types. METHODS: Self-efficacy and motivation for exercise and minutes per week of ET and ST were measured in 347 older veterans enrolled in a home-based PA counselling intervention. Regression analyses were used to compare high versus low self-efficacy and motivation and PA minutes in persons without arthritis, with arthritis alone, and with arthritis plus diabetes. RESULTS: Persons with arthritis alone reported lower self-efficacy for ET and ST than those without arthritis [odds ratio (OR)ET 0.71, 95% confidence interval (CI) 0.39­1.20; ORST 0.69, 95% CI 0.39­1.20]. A further reduction in self-efficacy for these two types of PA was observed for those with both arthritis and diabetes (ORET 0.65, 95% CI 0.44­0.92; ORST 0.64, 95% CI 0.44­0.93; trend p < 0.001). There was no trend towards a reduction in motivation for PA in those with arthritis alone or with arthritis and diabetes. Persons with arthritis exhibited higher motivation for ET than those without arthritis (ORET 1.85, 95% CI 1.12­3.33). There were no significant differences between the three groups in minutes of ET (p = 0.93), but persons with arthritis plus diabetes reported significantly less ST compared to individuals with arthritis only (p = 0.03). CONCLUSIONS: Despite reduced self-efficacy for ET and ST and less ST in older persons with arthritis, motivation for both PA types remains high, even in the presence of diabetes.

The impact of self-reported arthritis and diabetes on response to a home-based physical activity counselling intervention.

OBJECTIVES: Physical activity (PA) has the potential to improve outcomes in both arthritis and diabetes, but these conditions are rarely examined together. Our objective was to explore whether persons with arthritis alone or those with both arthritis and diabetes could improve amounts of PA with a home-based counselling intervention. METHODS: As part of the Veterans LIFE (Learning to Improve Fitness and Function in Elders) Study, veterans aged 70-92 were randomized to usual care or a 12-month PA counselling programme. Arthritis and diabetes were assessed by self-report. Mixed models were used to compare trajectories for minutes of endurance and strength training PA for persons with no arthritis (n = 85), arthritis (n = 178), and arthritis plus diabetes (n = 84). RESULTS: Recipients of PA counselling increased minutes of PA per week independent of disease status (treatment arm by time interaction p < 0.05 for both; endurance training time p = 0.0006 and strength training time p < 0.0001). Although PA was lower at each wave among persons with arthritis, and even more so among persons with arthritis plus diabetes, the presence of these conditions did not significantly influence response to the intervention (arthritis/diabetes group x time interactions p > 0.05 for both outcomes) as each group experienced a nearly twofold or greater increase in PA. CONCLUSIONS: A home-based PA intervention was effective in increasing minutes of weekly moderate intensity endurance and strength training PA in older veterans, even among those with arthritis or arthritis plus diabetes. This programme may serve as a useful model to improve outcomes in older persons with these pervasive diseases.

The Drosophila selenophosphate synthetase (selD) gene is required for development and cell proliferation.

To study the function of selenoproteins in development and growth we have used a lethal mutation (selD(ptuf)) of the Drosophila homologous selenophosphate synthetase (selD) gene. This enzyme is involved in the selenoprotein biosynthesis. The selD(ptuf) loss-of-function mutation causes aberrant cell proliferation and differentiation patterns in the brain and imaginal discs, as deduced from genetic mosaics, patterns of gene expression and analysis of cell cycle markers. In addition to that, selenium metabolism is also necessary for the ras/MAPKinase signal tansduction pathway. Therefore, the use of Drosophila imaginal discs and brain and in particular the selD(ptuf) mutation, provide an excellent model to investigate the role of selenoproteins in the regulation of cell proliferation, growth and differentiation.

In silico identification of novel selenoproteins in the Drosophila melanogaster genome.

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3'-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.

Correction of deficient CD34+ cells from peripheral blood after mobilization in a patient with congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is an inherited disease due to a deficiency in the uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme pathway. It is characterized by accumulation of uroporphyrin I in the bone marrow, peripheral blood, and other organs. The onset of most cases occurs in infancy and the main symptoms are cutaneous photosensitivity and hemolysis. For severe transfusion-dependent cases, when allogeneic cell transplantation cannot be performed, autografting of genetically modified primitive/stem cells is the only alternative. In the present study, efficient mobilization of peripheral blood primitive CD34(+) cells was performed on a young adult CEP patient. Retroviral transduction of this cell population with the therapeutic human UROS (hUS) gene resulted in both enzymatic and metabolic correction of CD34(+)-derived cells, as demonstrated by the increase in UROS activity and by a 53% drop in porphyrin accumulation. A 10-24% gene transfer efficiency was achieved in the most primitive cells, as demonstrated by the expression of enhanced green fluorescent protein (EGFP) in long-term culture-initiating cells (LTC-IC). Furthermore, gene expression remained stable during in vitro erythroid differentiation. Therefore, these results are promising for the future treatment of CEP patients by gene therapy.

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.

Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster.

Modulation of reactive oxygen species (ROS) plays a key role in signal transduction pathways. Selenoproteins act controlling the redox balance of the cell. We have studied how the alteration of the redox balance caused by patufet (selD(ptuf)), a null mutation in the Drosophila melanogaster selenophosphate synthetase 1 (sps1) gene, which codes for the SelD enzyme of the selenoprotein biosynthesis, affects the Ras/MAPK signalling pathway. The selD(ptuf) mutation dominantly suppresses the phenotypes in the eye and the wing caused by hyperactivation of the Ras/MAPK cassette and the activated forms of the Drosophila EGF receptor (DER) and Sevenless (Sev) receptor tyrosine kinases (RTKs), which signal in the eye and wing, respectively. No dominant interaction is observed with sensitized conditions in the Wnt, Notch, Insulin-Pi3K, and DPP signalling pathways. Our current hypothesis is that selenoproteins selectively modulate the Ras/MAPK signalling pathway through their antioxidant function. This is further supported by the fact that a selenoprotein-independent increase in ROS caused by the catalase amorphic Cat(n1) allele also reduces Ras/MAPK signalling. Here, we present the first evidence for the role of intracellular redox environment in signalling pathways in Drosophila as a whole organism.

Spinal flexibility and balance control among community-dwelling adults with and without Parkinson's disease.

BACKGROUND: One area of research that requires further elaboration is the relationship between impairments and functional limitations. By identifying specific contributors to functional limitations, it may be possible to establish intervention strategies, including exercise approaches, that can delay or ameliorate decline in function. The association between impaired spinal flexibility and functional limitations has not been studied in depth. The purposes of this study were to determine (a) the associations between spinal flexibility and functional limitations; (b) the relative contribution of spinal flexibility to specific functional limitations; and (c) how disease state (Parkinson's disease [PD] vs no PD) modified these relationships. METHODS: Participants included 251 community-dwelling adults, 56 of whom were with diagnosed PD and 195 were without PD or other specific disorders. Measures included spinal flexibility (i.e., functional axial rotation [FAR]) and configuration (i.e., thoracic kyphosis and lumbar lordosis), functional limitations (i.e., functional reach, supine-to-stand time, 10-m walk, and 360 degrees turn). RESULTS: Canonical correlation (Can R) demonstrated significant associations between spinal measures and functional limitations (Can R = .488, p = .0001). After controlling for age, gender, race, body mass index, comorbidity, confidence, and depression, a multivariate regression model demonstrated that spinal flexibility contributed significantly to functional reach (R2 = .334 for the overall model, p = .0001). Based on the parameter estimate of 0.026, the results prediet that FAR accounts for a 4.6-inch difference in reach distance between the least and most flexible of the participants. In addition, there were significant differences between almost all measurements for the PD compared with the non-PD participants. CONCLUSION: Results clearly implicate spinal flexibility as a contributor to functional reach, a measure of functional limitation and an established measure of balance control. Further work is needed to determine the extent to which spinal flexibility can be improved and the effect of that improvement on balance.

Brief report: birth status, medical complications, and social environment: individual differences in development of preterm, very low birth weight infants.

OBJECTIVE: To assess whether medical complications mediate the relationship between birth status (i.e., birth weight and gestational age) and developmental outcome of preterm, very low birth weight (VLBW) infants, as well as the role of the early social environment (maternal distress and social support) in infant development. METHOD: Birth status and medical complication information was collected during the child's NICU stay. Maternal distress was assessed with the Beck Depression Inventory and the Parenting Stress Index at 4 months corrected infant age. Social support was measured with the Dunst Scales at 4 months corrected age. Child development measures were collected at 4 and 13 months corrected age (Bayley MDI and PDI), and at 36 months chronological age (PPVT-R and Achenbach CBCL). RESULTS: Medical complications mediated the birth status-outcome relationship at 4 and 13 months, but not at 36 months. The 36-month outcomes were predicted by 4-month maternal distress and social support. CONCLUSIONS: Prematurity and VLBW are indirectly related to early developmental outcome through their association with medical complications. However, by 36 months, developmental outcomes are more closely related to aspects of the early social environment than to early physiological factors.

Co-existence of hereditary spherocytosis and a new red cell pyruvate kinase variant: PK mallorca.

BACKGROUND AND OBJECTIVE: A partial red blood cell (RBC) pyruvate-kinase (PK-R) deficiency was found in a patient with concomitant hereditary spherocytosis (HS) and chronic hemolytic anemia. Clinical, biological and molecular studies were performed in the patient, his parents and a brother, in order to characterize the specific PK-R gene mutation and the inheritance mechanism of the transmission of both red cell defects in this particular family. DESIGN AND METHODS: Conventional biological studies were used to identify the PK-LR gene mutation responsible for hereditary transmission of PK-R deficiency and HS. The family study was completed with genotypic and RBC membrane protein analyses in the patient and his family. RESULTS: Molecular study of the PK deficiency was performed in all the family members and demonstrated a heterozygous condition for the 1516 G->A (506Val->Ile) mutation at the PK-LR gene in both the patient and his mother. Since this mutation has not been reported previously, it is provisionally named PK "Mallorca". The study of RBC membrane proteins demonstrated the existence of partial band 3 and protein 4.2 deficiencies in the propositus and his father but not in the mother and brother, who were also studied. These results support the dominant mode of inheritance of HS and PK-LR gene in this family. INTERPRETATION AND CONCLUSIONS: HS and PK deficiency are not exceptional in Spain. The co-existence of both RBC defects in the same patient, however, is very rare; only a few cases have been described to date. Our findings suggest that performing an elementary RBC enzyme survey in all patients with HS would help to determine the real frequency of this apparently rare association.

Trophoblastic microemboli as a marker for preeclampsia-eclampsia in sudden unexpected maternal death: a case report and review of the literature.

The authors report the case of a 25-year-old white woman at 7 months' gestation who died suddenly and unexpectedly at home. Anatomic findings at autopsy included a tongue contusion, glomerulonephritis, changes indicative of systemic hypertension, and trophoblastic microemboli in the lungs. Review of the prenatal care record disclosed 3+ proteinuria 2 days before death. The features of the postmortem examination were consistent with clinically undiagnosed preeclampsia-eclampsia and glomerulonephritis. The authors discuss the rarity of fatal preeclampsia-eclampsia, the contribution of concomitant glomerulonephritis, and the significance of trophoblastic microemboli in the lungs.

Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men.

BACKGROUND: The age-related decline in maximal oxygen consumption is attenuated by habitual aerobic exercise. However, the relative effects of training on central and peripheral responses to exercise in older subjects are not known. The present study assessed the contribution of central and peripheral responses to the age-associated decline in peak oxygen consumption and compared the effect of exercise training in healthy older and younger subjects. METHODS AND RESULTS: Ten older and 13 younger men underwent invasive measurement of central and peripheral cardiovascular responses during an upright, staged cycle exercise test before and after a 3-month period of exercise training with cycle ergometry. At baseline, cardiac output and AV oxygen difference during exercise were significantly lower in older subjects. With training, the older and younger groups increased maximal oxygen consumption by 17.8% and 20.2%, respectively. Peak cardiac output was unchanged in both groups. Systemic AV oxygen difference increased 14.4% in the older group and 14.3% in the younger group and accounted for changes in peak oxygen consumption. Peak leg blood flow increased by 50% in older subjects, whereas the younger group showed no significant change. There was no change in peak leg oxygen extraction in the older group, but in the younger group, leg AV oxygen difference increased by 15.4%. CONCLUSIONS: These findings suggest that the age-related decline in maximal oxygen consumption results from a reversible deconditioning effect on the distribution of cardiac output to exercising muscle and an age-related reduction in cardiac output reserve.

Fatal laryngeal injury in an achondroplastic dwarf secondary to airbag deployment.

We report the case of an unrestrained driver with achondroplastic dwarfism who suffered a fatal anterior neck injury when her airbag deployed as she rear-ended another vehicle at 30-40 mph. Her short stature and short limbs required her to sit within a handbreadth of the steering wheel, which probably allowed the airbag or airbag cover to strike her neck as it opened. This is the first reported case of fatal injury to a driver with achondroplastic dwarfism.

Spinal-flexibility-plus-aerobic versus aerobic-only training: effect of a randomized clinical trial on function in at-risk older adults.

BACKGROUND: As exercise is associated with favorable health outcomes, impaired older adults may benefit from specialized exercise interventions to achieve gains in function. The purpose of this study was to determine the added benefit of a spinal flexibility-plus-aerobic exercise intervention versus aerobic-only exercise on function among community-dwelling elders. METHODS: We employed a randomized clinical trial consisting of 3 months of supervised exercise followed by 6 months of home-based exercise with telephone follow-up. A total of 210 impaired males and females over age 64 enrolled in this study. Of these, 134 were randomly assigned to either spinal flexibility-plus-aerobic exercise or aerobic-only exercise, with 116 individuals completing the study. Primary outcomes obtained at baseline, after 3 months of supervised exercise, and after 6 months of home-based exercise included: axial rotation, maximal oxygen uptake (VO2max); functional reach, timed-bed-mobility; and the Physical Function Scale (PhysFunction) of the Medical Outcomes Study SF-36. RESULTS: Differences between the two interventions were minimal. Overall change scores for both groups combined indicated significant improvement for: axial rotation (p=.001), VO2max (p=.0001), and PhysFunction (p=.0016). Secondary improvements were noted for overall health (p=.0025) and reduced symptoms (p=.0008). Differences between groups were significant only for VO2max (p=.0014) at 3 months with the aerobic-only group improving twice as much in aerobic capacity as the spinal flexibility-plus-aerobic group. Repeated measures indicated both groups improved during the supervised portion of the intervention but tended to return toward baseline following the home-based portion of the trial. CONCLUSIONS: Gains in physical functioning and perceived overall health are obtained with moderate aerobic exercise. No differential improvements were noted for the spinal flexibility-plus-aerobic intervention.

[Molecular study of red cell pyruvate kinase deficiency in 15 patients with chronic hemolytic anemia. Group of Erythropathology of Hematology and hemotherapy Association of Spain (HHAS)]. / Estudio molecular del déficit de piruvatocinasa eritrocitaria en 15 pacientes con anemia hemolítica crónica. Grupo de Eritropatología de la Asociación Española de Hematología y Hemoterapia (AEHH).

BACKGROUND: Identification of RBC pyruvate-kinase (PK) gene mutations by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) followed by PK gene sequencing in positive cases has been assessed and the results obtained with a preliminary study of 15 unrelated patients of Spanish origin are presented. PATIENTS AND METHODS: Patients have been classified into two different groups: group 1, propositus (15 cases), and group 2, relatives of the patients included in group 1 (10 males and 5 females). In group 1, a PCR was followed by SSCP and sequencing, and in group 2, the PCR was followed by digestion with specific restriction endonucleases (PCR-ER). RESULTS: Group 1: from 15 patients included in the study 2 were identified as homozygous, 4 as heterozygous and 9 as compound heterozygous. In this group, were identify 26 affected alleles with 11 different mutations: T1456 10 alleles (38.6%), T721 3 alleles (11.6%), A1010, C514, C1015 and T1223 2 alleles (7.7%), and C1070, A1291, T1508, A1595 y T1675 one allele. Relatives from 8 out of 15 patients from group 1 showed the following pattern: homozygous (one case), heterozygous (10 cases), compound heterozygous (2 cases) and normal (2 cases). CONCLUSIONS: SSCP procedure followed by direct gene sequencing in positive cases is fast and simple enough to allow the identification of PK deficient variants, avoiding the need of biochemical characterisation of semipurified deficient enzyme, which is more cumbersome and time consuming. In addition, the PCR-ER method is a very useful tool for screening of the most frequent molecular variants, as well as, for the detection of the carrier condition of this enzymopathy (family studies).

Reliability of physical performance tests in four different randomized clinical trials.

OBJECTIVES: (1) To assess the test-retest reliability of physical performance tests in subject groups with different levels of impairment and disability, and (2) to assess the stability of these tests over different time intervals. DESIGN: Test-retest, repeated measures reliability design. SETTING: (1) A university's center for aging and research center, (2) a continuing care retirement community, and (3) an extended care and rehabilitation center at a Veterans Affairs medical center. SUBJECTS: Twenty-four community-dwelling elders, 15 community-dwelling elders with Parkinson disease, 12 older women with vertebral osteoporosis and compression fractures, and 14 elderly nursing home residents. MEASURES: Lower extremity isometric strength (ankle dorsiflexion, hip abduction), spinal configuration (thoracic kyphosis, lumbar lordosis), lumbosacral motion (flexion, extension), and timed measures of the ability to get in and to get out of bed at a usual pace. RESULTS: Most of the within-group intraclass correlation coefficients (ICCs) were good to excellent (.70 to .97). Overall, ICCs for all groups combined were between .70 and .96, and no decrement in reliability was noted after controlling for group membership. In addition, no decrement in the ICC was observed for short (1 day) vs. longer (1 week) intervals of testing. CONCLUSIONS: These performance-based measures may be used reliably across a wider range of testing environments and elderly populations than has been reported.

Long-term storage at -80 degrees C of hematopoietic progenitor cells with 5-percent dimethyl sulfoxide as the sole cryoprotectant.

BACKGROUND: Hematopoietic progenitor cells (HPCs) can be cryopreserved and stored below -120 degrees C in liquid nitrogen or at -80 degrees C in mechanical freezers. STUDY DESIGN AND METHODS: The feasibility of long-term storage of HPCs at -80 degrees C was investigated. The studies included a comparison of 5- and 10-percent dimethyl sulfoxide (DMSO) as cryoprotectant at various lengths of storage time. Mononuclear cell (MNC) recovery and viability and colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) recovery assays were performed. The peripheral blood HPCs of 24 consecutive patients included in the program of autologous transplantation were studied. RESULTS: The MNC viability decreased progressively with the length of time from cryopreservation, reaching 32 percent after 31 months of storage. The recovery rates of CFU-GM and BFU-E also decreased progressively with the duration of frozen storage, to 50 and 43.5 percent, respectively, after 12 months and to 0 percent (both) after 24 months. At 6 months of storage, MNC viability was 80 percent, and CFU-GM and BFU-E recovery was 63.5 and 80.5 percent, respectively. There were no differences between MNCs cryopreserved with 5- or 10-percent DMSO in terms of cell viability. There were no differences between CFU-GM recovery or BFU-E recovery from HPCs cryopreserved in 5- or 10-percent DMSO. Patients given HPCs stored in these conditions for periods ranging between 123 and 202 days showed a complete and rapid hematologic recovery. CONCLUSION: HPCs can be cryopreserved at -80 degrees C with 5-percent DMSO and stored at -80 degrees C no longer than 6 months. A 5-percent DMSO concentration is comparable to a with 10-percent concentration in terms of recovery and MNC viability.

Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH).

The PK-LR gene has been studied in 12 unrelated patients with red cell pyruvate kinase deficiency and hereditary nonspherocytic haemolytic anaemia (CNSHA). The entire codifying region of the R-type PK gene and the flanking intronic regions were analysed by single-stranded conformation polymorphism (SSCP) followed by direct sequencing of abnormal DNA. 10 different mutations were identified in 22/24 alleles at risk. Eight of these were missense mutations that caused the following single amino acid changes: G514C (172Glu-Gln), G1010A (337Arg-Gln), G1015C (339Asp-Gln), T1070C (357Ile-Thr), C1223T (408Thr-Ile), G1291A (431Ala-Thr), C1456T (486Arg-Trp) and G1595A (532Arg-Gln). Two were nonsense mutations: G721T (241Glu-Stop) and C1675T (559Arg-Stop). 7/22 alleles demonstrated the same C1456 --> T mutation. The study of the polymorphic site at nucleotide (nt) 1705 performed in all cases disclosed a 1705 C/C mutation in 10 and a 1705 A/C mutation in three. This is the first report on the presence of several different L-type PK gene mutations within Spanish population. Furthermore, from the PK gene mutations found, six were unique and not previously described (1015C, 1070C, 1223T, 1291A, 1595A and 1675T) and one (C1456T) seems to be predominant in Spain. Interestingly, no case with the 1529A mutation commonly found in Northern European populations was present here.

Is there a threshold between peak oxygen uptake and self-reported physical functioning in older adults?

PURPOSE: Few studies have examined the relationship between directly measured oxygen uptake (VO2) and self-reported physical function (PF). The purpose of this study was: 1) to examine the relationship between peak V02 and PF and 2) to determine whether a threshold or cut point exist that distinguishes between individuals reporting required assistance in the performance of functional tasks (low PF) and those who report ability to perform tasks independently (high PF). METHODS: Participants were 161 community-dwelling adults, ages 65-90, who had a baseline evaluation for a clinical trail that included measurement of peak V02 and PF consisted of a summary score combining scores from the Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire, Nagi Disability Study. Rosow-Breslau Scale, Physical Function Scale of the Medical Outcomes Study, and the Falls Efficacy Scale. Decision tree, cubic spline, and logistic regression analyses explored these relationships with age, gender, education, race, body mass index, depression, and total number of chronic diseases included as important covariates. RESULTS: Among all covariates examined, peak V02 was most strongly associated with (P = 0.004) with PF. There was not threshold effect. Decision tree analyses indicated that 18.3 mL.kg-1.min-1 was the optimal cut point distinguishing between low PF and High PG (P < 0.0001). Between-gender differences in PF (P = 0.002) were no longer significant when peak V02 was included in the PF model (P = 0.17). CONCLUSIONS: These data indicate that individuals with a V02 < 18 mL.kg-1min-1 report significant difficulty in the performance of daily tasks and that differences in peak V02 may explain, in part, why women report more impairment in PF.