João Marcos Domingues Dias

Ticks produce highly selective chemokine binding proteins with antiinflammatory activity

Bloodsucking parasites such as ticks have evolved a wide variety of immunomodulatory proteins that are secreted in their saliva, allowing them to feed for long periods of time without being detected by the host immune system. One possible strategy used by ticks to evade the host immune response is to produce proteins that selectively bind and neutralize the chemokines that normally recruit cells of the innate immune system that protect the host from parasites. We have identified distinct cDNAs encoding novel chemokine binding proteins (CHPBs), which we have termed Evasins, using an expression cloning approach. These CHBPs have unusually stringent chemokine selectivity, differentiating them from broader spectrum viral CHBPs. Evasin-1 binds to CCL3, CCL4, and CCL18; Evasin-3 binds to CXCL8 and CXCL1; and Evasin-4 binds to CCL5 and CCL11. We report the characterization of Evasin-1 and -3, which are unrelated in primary sequence and tertiary structure, and reveal novel folds. Administration of recombinant Evasin-1 and -3 in animal models of disease demonstrates that they have potent antiinflammatory properties. These novel CHBPs designed by nature are even smaller than the recently described single-domain antibodies (Hollinger, P., and P.J. Hudson. 2005. Nat. Biotechnol. 23:1126–1136), and may be therapeutically useful as novel antiinflammatory agents in the future.

Cross-cultural adaptation and evaluation of the psychometric properties of the Falls Efficacy Scale-International Among Elderly Brazilians (FES-I-BRAZIL).

OBJECTIVES To culturally adapt the Falls Efficacy Scale-International (FES-I) and assess its psychometric properties in a sample of community-dwelling elderly Brazilians. METHODS The instrument was translated into Brazilian Portuguese and culturally adapted to the Brazilian population (FES-I-Brazil) as recommended by the Prevention of Falls Network Europe. FES-I-Brazil was applied to 163 elderly people (73.44+/-5.51 years), and the demographic data and history of falls were also collected. From this group, 58 participants were randomly distributed to evaluate reliability. The reliability was analyzed using the intraclass correlation coefficient (ICC) and the internal consistency, using Cronbachs alpha coefficient (alpha). The internal structure of FES-I-Brazil was evaluated by means of exploratory factor analysis. The logistic regression model was used to determine which tasks on the scale were more relevant for discriminating falls. To analyze the sensitivity and specificity of FES-I-Brazil, the receiver operating characteristic (ROC) curve was used. RESULTS The internal consistency of FES-I-Brazil was alpha=0.93, and the intra- and inter-examiner reliability were ICC=0.84 and 0.91, respectively. Factor analysis suggested two factors: concern about falling during social activities and activities of daily living (basic and instrumental), and postural control tasks. FES-I-Brazil scores > or = 23 suggested an association with a previous history of sporadic falls, whereas scores > or = 31 suggested an association with recurrent falls. CONCLUSIONS FES-I-Brazil was shown to be semantically, linguistically and psychometrically appropriate to evaluate the fear of falling in the community-dwelling Brazilian elderly population.

Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women

Biomarkers are important factors in the identification of the frail elderly (higher risk of developing disease) and in assessing the impact of PTI. On the other hand, BDNF has been related to neuroprotection in a series of central nervous system diseases in older age. The levels of BDNF in groups of elderly women classified according to Fried phenotype (non-frail and pre-frail) were compared. We assessed the impact of a PTI on BDNF levels. A convenience sample of 48 elderly women was randomly selected. The PTI group was composed by 20 elderly women selected from this group. Plasma neurotrophic factors, such as BDNF, glial-derived neutrophic factor (GDNF), and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay (ELISA). Timed-up-and-go (TUG) test, hand-grip and work/body weight were evaluated before and after the intervention. Plasma concentrations of BDNF were significantly higher in non-frail in comparison to pre-frail elderly women. After the PTI, higher levels of BDNF were found in elderly women (before 351±68 pg/ml and after 593±79 pg/ml; p<0.001). Both groups had an increase in BDNF levels after the PTI. The low levels of BDNF in pre-frail elderly women suggest that this neurotrophic factor may be a key pathophysiological mediator in the syndrome of frailty. The fact that PTI increased BDNF levels in both groups suggests that it may be possible to modify this phenotype.

Estudo da relação entre função muscular, mobilidade funcional e nível de atividade física em idosos comunitários

OBJECTIVES to evaluate the relationship between lower extremity muscle function, calf circumference (CC), handgrip strength (HG), functional mobility and level of physical activity among age groups (65-69, 70-79, 80+) of older adults (men and women) and to identify the best parameter for screening muscle function loss in the elderly. METHODS 81 community-dwelling elderly (42 women and 39 men) participated. Walking speed (Multisprint Kit), HG (Jamar dynamometer), hip, knee and ankle muscle function (Biodex isokinetic dynamometer), level of physical activity (Human Activity Profile) and CC (tape measure) were evaluated. ANOVA, Pearson correlation and ROC curves were used for statistical analysis. RESULTS Dominant CC (34.9±3 vs 37.7±3.6), habitual (1.1±0.2 vs 1.2±0.2) and fast (1.4±0.3 vs 1.7±0.3) walking speed, HG (23.8±7.5 vs 31.8±10.3), average peak torque and average hip, knee and ankle power (p<0.05) were lower for the 80+ group than for the 65-69 year-olds. There were no differences in physical activity level among age groups. Moderate significant correlations were found between muscle function parameters, walking speed and HG; a fair degree of relationship was found between muscle function parameters, CC and level of physical activity (p<0.05). The ROC curve analysis suggested a cutoff point of 14.51 Kgf for screening muscle function loss in elderly women (p=0.03). CONCLUSIONS This study demonstrated an association between muscle function, HG and fast walking speed, a decrease in these parameters with age and the possibility of using HG to screen for muscle function of the lower extremities.

Muscle strength, muscle balance, physical function and plasma interleukin-6 (IL-6) levels in elderly women with knee osteoarthritis (OA)

An increased circulating level of inflammatory cytokines has been associated with sarcopenia, functional disability, chronic diseases, and mortality in the elderly. Osteoarthritis (OA) is a disease common to this population, the seriousness of articular degeneration has been associated to the increase in some cytokines, IL-6 among them. The aim of the present study was to correlate IL-6 plasma levels with muscle strength, endurance, muscle balance hamstring/quadriceps (H/Q) and physical function in 80 elderly women (71.2 ± 5.3) with knee OA. IL-6 was measured using enzyme-linked immunosorbent assay (ELISA). Quadriceps and hamstring muscle strength, endurance and hamstring-quadriceps muscle balance were assessed using a Biodex system 3 pro(®) isokinetic dynamometer. Physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Spearmans correlation coefficient was used to explore the relationship between the outcomes at the significance level of α=0.05. IL-6 was inversely correlated to the endurance of the hamstring muscles (r=-0.232; p=0.03) and muscle balance (H/Q) on the lower right side at 180°/s (r=-0.254; p=0.023). No significant correlation between IL-6, muscle strength and physical function was found. Our results show that elevated levels of IL-6 may possibly contribute to the reduction of the endurance of hamstring muscles and H/Q muscle balance in the elderly studied.

Characteristics associated with activity restriction induced by fear of falling in community-dwelling elderly

OBJECTIVES The aim of this study was to determine the social-demographic, clinical, functional and psychological factors associated to activity restriction due to fear of falling in community-dwelling elderly and identify which variables best discriminate groups of elderly with different levels of activity restriction and fear of falling. METHODS One hundred and thirteen community-dwelling elderly (74.5±7 years old) participated in the study. Activity restriction induced by fear of falling, previous falls, fall related self-efficacy, frailty phenotype, functional capacity, depressive symptoms, health self-perception, socio-demographic and clinical factors were assessed. Descriptive statistics, chi-square, ANOVA and Kruskal Wallis tests were used to analyze the associations between activity restriction due to fear of falling and all other variables. Path analysis (CHAID) method was used to verify which variables better discriminated groups in relation to activity restriction (α=0.05). RESULTS The participants who reported fear of falling and activity restriction demonstrated higher depression (p=0.038), lower fall related self-efficacy (p<0.001), lower gait velocity (p=0.043) and independence level for instrumental daily living activities (p=0.017), higher number of diseases (p=0.048), worse health self-perception (p=0.040) and more depressive symptom (p=0.023). The best variables to discriminate groups were depression (p=0.004), exhaustion (frailty phenotype) (p=0.010) and social participation activities (p=0.016). CONCLUSION Activity restriction due to fear of falling may have negative effects on functional capacity and psychological aspects in community-dwelling elderly. Psychosocial factors seem to better discriminate the elderly who avoid activities due to fear of falling.

Relação entre intensidade de dor e capacidade funcional em indivíduos obesos com osteoartrite de joelho

BACKGROUND: Knee osteoarthritis is a chronic disease that affects joint cartilage, causing bone structure alterations, pain and stiffness during movement. Obesity is one of its principal risk factors. Complaints about functional disability are frequent, especially for locomotion activities, which people with knee osteoarthritis perform slower. With the increasing levels of obesity in Brazil, it is important to understand how knee osteoarthritis affects human functional capacity, in order to devise treatment and prevention measures. OBJECTIVE: To examine the influence of pain intensity, radiographic severity, obesity level and symptom duration on the functional capacity of obese individuals with knee osteoarthritis. METHOD: Pain intensity was measured using the Western Ontario and McMaster Universities Index (WOMAC) questionnaire and during functional capacity tests. Radiographic severity was analyzed using the Kellgren-Lawrence classification and the obesity level was assessed using body mass index (BMI). Four functional velocity tests were performed: usual gait, fast gait, ascending stairs and descending stairs. RESULTS: The sample consisted of 31 women and 4 men, with mean age of 51.65 ± 10.72 years and BMI of 41.16 ± 8.37 kg/m2. The greatest intensity of pain was reported during stair activities. Only pain intensity presented significant correlations with the results from the velocity tests. CONCLUSION: Pain intensity is a factor that influences functional activity performance among obese individuals with knee osteoarthritis. Further studies are necessary for identifying the determining factors for functional capacity in such populations.

Prevalência de fragilidade e fatores associados em idosos comunitários de Belo Horizonte, Minas Gerais, Brasil: dados do estudo FIBRA

The prevalence of frailty varies greatly and has received insufficient attention in developing countries. This study aimed to identify the prevalence of frailty and associated factors among the elderly in Belo Horizonte, Minas Gerais State, Brazil. Clinical, functional, and socio-demographic factors were analyzed. An ordinal regression model was used to verify conditions associated with frailty and to determine odds ratios ( α= 0.05). Prevalence rates were 46.3% for pre-frailty was 8.7% for weakness. Pre-frail and frail elderly, respectively, showed higher and increasing odds ratios for dependency in instrumental activities of daily living; restrictions in advanced activities of daily living; use of walking aids; comorbidities; falls; depressive symptoms; lower self-efficacy in preventing falls; hospitalization; and advanced age. The study identified a high percentage of frail states associated with higher odds of adverse health conditions, especially related to disability.The prevalence of frailty varies greatly and has received insufficient attention in developing countries. This study aimed to identify the prevalence of frailty and associated factors among the elderly in Belo Horizonte, Minas Gerais State, Brazil. Clinical, functional, and socio-demographic factors were analyzed. An ordinal regression model was used to verify conditions associated with frailty and to determine odds ratios ( α= 0.05). Prevalence rates were 46.3% for pre-frailty was 8.7% for weakness. Pre-frail and frail elderly, respectively, showed higher and increasing odds ratios for dependency in instrumental activities of daily living; restrictions in advanced activities of daily living; use of walking aids; comorbidities; falls; depressive symptoms; lower self-efficacy in preventing falls; hospitalization; and advanced age. The study identified a high percentage of frail states associated with higher odds of adverse health conditions, especially related to disability.

Effects of 174 G/C polymorphism in the promoter region of the interleukin-6 gene on plasma IL-6 levels and muscle strength in elderly women

We investigated the effect of -174 G/C single-nucleotide polymorphism in the promoter region of the IL6 gene on plasma IL-6 levels and muscle strength, and the relationship between IL-6 levels and muscle strength in elderly women. The sample consisted of 199 elderly residents (73.0 ± 7.8 years old) from rest homes and the community in Belo Horizonte, MG, Brazil. -174 G/C polymorphism was determined by direct sequencing of the product by PCR, and plasma IL-6 concentrations were measured by ELISA. Muscle strength in the knee joint was evaluated using a Biodex System 3 Pro® isokinetic dynamometer. ANCOVA was used to determine the effect of polymorphism on IL-6 levels and muscle strength, and the Pearson correlation coefficient to assess the relationship between IL-6 levels and muscle strength. -174 G/C polymorphism was associated with the plasma IL-6 levels of elderly women (P < 0.01) since homozygotes for the G allele showed high IL-6 levels (GG 3.85 pg/mL, GC + CC 2.13 pg/mL). There was no association of polymorphism on muscle strength (P > 0.05). No association was found between IL-6 levels and knee extensor muscle (r = 0.087, P = 0.306) or flexor (r = -0.011, P = 0.894) strength. An interaction between -174 G/C polymorphism and housing conditions of the sample of elderly women was identified, with the effect of genotype on IL-6 levels being higher in the institutionalized elderly. These results support the evidence that -174 G/C polymorphism of the IL6 gene associates with individual variability of plasma IL-6 levels in elderly women.

Relação da função muscular respiratória e de membros inferiores de idosos comunitários com a capacidade funcional avaliada por teste de caminhada

BACKGROUND: Sarcopenia is the most significant factor in the decline of peripheral and respiratory muscle strength. It can lead to progressive disability, loss of independence and impaired functional capacity. OBJECTIVES: To determine the strength of respiratory muscles (maximal inspiratory pressure - MIP and maximal expiratory pressure - MEP) and lower limb muscles, and to explore the possible relationships between these variables and the functional capacity of the elderly. METHODS: Sixty-five elderly patients (71.7±4.9 years old) took part in the study. Isokinetic dynamometry was used to assess the knee flexors and extensors, an analog vacuum manometer was used to assess the respiratory muscles, and the six-minute walking test was used as an outcome of functional capacity. The Mann-Whitney test and Students t-test were used for gender comparison. The relationships were investigated using Pearsons correlation. The significance level was p<0.05. RESULTS: The lower limb and respiratory muscle strength variables and the walking distance variables were higher in men than women (p<0.05). Moderate and significant correlations were found between these variables (p<0.001). The higher values were between right knee extensor average peak torque (APT) and MIP (r=0.587), left knee flexor APT and MEP (r=0.638), as well as between walking distance and left knee extensor average power (AP; r=0.614), right knee flexor AP (r=0.539), MIP (r=0.508) and MEP (r=0.541) respectively. CONCLUSIONS: The relationship between walking distance and respiratory and lower limb muscle strength found in this study suggests that optimizing these functions may contribute to maintaining and improving functional capacity in the elderly.