Resistance exercise training improves heart rate variability in women with fibromyalgia

Fibromyalgia (FM) is characterized by generalized muscle pain, low muscle strength and autonomic dysfunction. Heart rate (HR) variability (HRV) is reduced in individuals with FM increasing their risk for cardiovascular morbidity and mortality. We tested the hypothesis that resistance exercise training (RET) improves HRV, baroreflex sensitivity (BRS) and muscle strength in women with FM. Women with FM (n = 10) and healthy controls (n = 9), aged 27-60 years, were compared at baseline. Only women with FM underwent supervised RET 2 days per week for 16 weeks. Baseline and post-training measurements included HRV and spontaneous baroreflex sensitivity (BRS, alpha index) from continuous electrocardiogram and blood pressure (BP) recorded with finger plethysmography during 5 min in the supine position. RR interval, total power, log transformed (Ln) squared root of the standard deviation of RR interval (RMSSD), low-frequency power and BRS were lower (P<0.05), and HR and pulse pressure were higher (P<0.05) in women with FM than in healthy controls. After RET, mean (SEM) total power increased (387 +/- 170 ms(2), P<0.05), RMSSD increased (0.18 +/- 0.08 Ln ms, P<0.05) and Ln of high-frequency power increased (0.54 +/- 0.27 Ln ms(2), P = 0.08) in women with FM. Upper and lower body muscle strength increased by 63% and 49% (P<0.001), and pain perception decreased by 39% in women with FM. There were no changes in BRS, HR and BP after RET. Our study demonstrates that RET improves total power, cardiac parasympathetic tone, pain perception and muscle strength in women with FM who had autonomic dysfunction before the exercise programme.     

Antimicrobial evaluation of methanolic extract of Colliandra surinamensis on some pathogenic organisms

The crude extract of Colliandra surinamensis is used in traditional medicine for the treatment of some diseases/infections. The crude extract obtained from the flower of Colliandra surinamensis was found to have antimicrobial activity against some Gram positive organisms such as Staphylococcus aureus, Bacillus subtilis and Steptococcus species. The performance of the extract against the bacteria isolates was favorably comparable with established commercial antibacterial agents.     

Cadherin puncta are interdigitated dynamic actin protrusions necessary for stable cadherin adhesion

Cadherins harness the actin cytoskeleton to build cohesive sheets of cells using paradoxically weak bonds, but the molecular mechanisms are poorly understood. In one popular model, actin organizes cadherins into large, micrometer-sized clusters known as puncta. Myosin is thought to pull on these puncta to generate strong adhesion. Here, however, we show that cadherin puncta are actually interdigitated actin microspikes generated by actin polymerization mediated by three factors (Arp2/3, EVL, and CRMP-1). The convoluted membranes in these regions give the impression of cadherin clustering by fluorescence microscopy, but the ratio of cadherin to membrane is constant. Nevertheless, these interlocking fingers of membrane are important for adhesion because perturbing their formation disrupts cell adhesion. In contrast, blocking myosin-dependent contractility does not disrupt either the interdigitated microspikes or lateral membrane adhesion. “Puncta” are zones of strong cell–cell adhesion not due to cadherin clustering but that occur because the interdigitated microspikes expand the surface area available for adhesive bond formation and increase the asperity of the cell surface to promote friction between cells.

Cadherins are homophilic adhesion molecules necessary for the formation and maintenance of all solid tissues (1). While the cadherin extracellular domain is sufficient for homophilic binding, strong adhesion requires the actin cytoskeleton, but the mechanism is not known. The two most popular models are that actin promotes lateral clustering of cadherins (2–8) or that myosin-dependent contractile forces pull on adhesive junctions to make them stronger (9–13). The two mechanisms might work in concert because the known links between cadherins and actin are tension dependent (6). This hybrid model can explain how cells transmit contractile forces to another cell to drive morphogenetic cell movements (1), but whether tension on clusters explains the role of actin in stabilizing adhesion is another matter. In some cell types, cadherins concentrate along a circumferential actin belt at the apical junction (Fig. 1A) (14). The actin belt is contractile, and the cadherin–catenin complex along it is under tension. But the role of contractility in adhesion is not clear. Certainly, many cells build cadherin-dependent contacts in the absence of a defined circumferential actin belt (15). Nevertheless, the consensus is that the primary functions of the actin cytoskeleton in strengthening cell–cell adhesion are to gather cadherins into clusters and pull on them (16).Open in a separate windowFig. 1.Mesoscale puncta at the cell–cell interface are convoluted plasma membranes. (A, Top) A cell in the canine kidney epithelial cell sheets (MDCK) expresses E-cadherin–GFP. The red box shows the pseudocolored apical membrane and a tilted part of the lateral membrane, which are viewed en face. Asterisks are puncta. (A, Bottom) Three domains of epithelial cells. One of the lateral membranes is shaded gray. The horizontal plane indicates the focal plane for lateral domains in B–G. (B) Two neighboring cells coexpress a plasma membrane-targeted GFP (CAAX-GFP) and an E-cadherin fused to mCherry (magenta). Arrows are microspikes at apical junctions (21). Arrowheads are voids between E-cadherin puncta. Asterisks are membrane puncta. Ves are intracellular vesicles. The plots show the density of markers along membranes and the cadherin-to-membrane ratio (red line = 1). The correlation coefficient (r) between the two channels is shown. (C) Two neighboring cells coexpressing E-cadherin–GFP (green) are costained with a lipophilic dye (magenta). (D) Two neighboring cells coexpressing membrane YFP (green) are stained for endogenous β-catenin staining (magenta). The plot shows the 25 to 50 to 75% range of r of the two channels’ linescan (“measured”) and of r when one of the linescan is inverted (“random”); n = 186 junctions; two-sided t test. (E) The curves show the averaged linescan orthogonal to the membrane at flat regions (solid line) and puncta (dashed line and asterisks). (Inset) Mean membrane thickness (±SEM). n = 30 flat regions and 58 puncta in six cells. ***P < 6 × 10⁻⁸, two-sided t test. (F) Fluorescence recovery after photobleaching (FRAP) of E-cadherin in a flat region (solid line) and a punctum (dashed line). The curves show the intensity corrected for background bleaching. The scatter plots show the correlation between stability parameters with punctum size, which is expressed as membrane area. (G) FRAP of the lipidated GFP. Punctum #3 (circle) is bleached. The plot shows the intensity of each punctum (solid lines) and background (dashed line). (Inset) −0.5 to 0.5 s. (H) Two models to explain mesoscale cadherin puncta (color coding of density and ratio plots same as B–D). All images show live cells except for D. (All scale bars, 1 μm.)While contractile actin continues to dominate thinking in cadherin biology, recent results have shown an important role for actin assembly factors like Arp2/3, Ena/VASP proteins, and CRMP-1 in assembling actin at cell boundaries in epithelia and endothelia (17–21). These actin assembly factors are associated with actin protrusive activity like lamellipodia in migrating cells (19). The results open the possibility that actin polymerization–dependent pushing forces might play an important role in converting weak cadherin bonds into strong adhesion (22). Here, we test in polarized kidney epithelial cells (Madin–Darby Canine Kidney [MDCK] cells) in cell sheets whether this mechanism can explain the prominent cadherin clusters (often referred to as puncta) that serve as sites for strong cell–cell adhesion (23–25).     

Exploring genotype‐phenotype relationships in the CDKL5 deficiency disorder using an international dataset

Characterized by early‐onset seizures, global developmental delay and severe motor deficits, CDKL5 deficiency disorder is caused by pathogenic variants in the cyclin‐dependent kinase‐like 5 gene. Previous efforts to investigate genotype‐phenotype relationships have been limited due to small numbers of recurrent mutations and small cohort sizes. Using data from the International CDKL5 Disorder Database we examined genotype‐phenotype relationships for 13 recurrent CDKL5 variants and the previously analyzed historic variant groupings. We have applied the CDKL5 Developmental Score (CDS) and an adapted version of the CDKL5 Clinical Severity Assessment (CCSA), to grade the severity of phenotype and developmental outcomes for 285 individuals with CDKL5 variants. Comparisons of adapted CCSA and CDS between recurrent variants and variant groups were performed using multiple linear regression adjusting for age and sex. Individuals with the missense variant, p.Arg178Trp, had the highest mean adapted CCSA and lowest mean developmental scores. Other variants producing severe phenotypes included p.Arg559* and p.Arg178Gln. Variants producing milder phenotypes included p.Arg134*, p.Arg550*, and p.Glu55Argfs*20. There are observed differences in phenotype severity and developmental outcomes for individuals with different CDKL5 variants. However, the historic variant groupings did not seem to reflect differences in phenotype severity or developmental outcomes as clearly as analyzed by individual variants.     

Influence of carbohydrate supplementation on skill performance during a soccer match simulation

ObjectivesThis study investigated the influence of carbohydrate supplementation on skill performance throughout exercise that replicates soccer match-play.DesignExperimentation was conducted in a randomised, double-blind and cross-over study design.MethodsAfter familiarization, 15 professional academy soccer players completed a soccer match simulation incorporating passing, dribbling and shooting on two separate occasions. Participants received a 6% carbohydrate–electrolyte solution (CHO) or electrolyte solution (PL). Precision, success rate, ball speed and an overall index (speed-precision-success; SPS) were determined for all skills. Blood samples were taken at rest, immediately before exercise, every 15 min during exercise (first half: 15, 30 and 45 min; second half: 60, 75 and 90 min), and 10 min into the half time (half-time).ResultsCarbohydrate supplementation influenced shooting (time × treatment interaction: p < 0.05), where CHO attenuated the decline in shot speed and SPS index. Supplementation did not affect passing or dribbling. Blood glucose responses to exercise were influenced by supplementation (time × treatment interaction: p < 0.05), where concentrations were higher at 45 min and during half-time in CHO compared with PL. Blood glucose concentrations reduced by 30 ± 1% between half-time and 60 min in CHO.ConclusionsCarbohydrate supplementation attenuated decrements in shooting performance during simulated soccer match-play; however, further research is warranted to optimise carbohydrate supplementation regimes for high-intensity intermittent sports.     

Soluble flagellin, FliC, induces an Ag-specific Th2 response, yet promotes T-bet-regulated Th1 clearance of Salmonella typhimurium infection

Clearance of disseminated Salmonella infection requires bacterial-specific Th1 cells and IFN-γ production, and Th1-promoting vaccines are likely to help control these infections. Consequently, vaccine design has focused on developing Th1-polarizing adjuvants or Ag that naturally induce Th1 responses. In this study, we show that, in mice, immunization with soluble, recombinant FliC protein flagellin (sFliC) induces Th2 responses as evidenced by Ag-specific GATA-3, IL-4 mRNA, and protein induction in CD62L(lo) CD4(+) T cells without associated IFN-γ production. Despite these Th2 features, sFliC immunization can enhance the development of protective Th1 immunity during subsequent Salmonella infection in an Ab-independent, T-cell-dependent manner. Salmonella infection in sFliC-immunized mice resulted in augmented Th1 responses, with greater bacterial clearance and increased numbers of IFN-γ-producing CD4(+) T cells, despite the early induction of Th2 features to sFliC. The augmented Th1 immunity after sFliC immunization was regulated by T-bet although T-bet is dispensable for primary responses to sFliC. These findings show that there can be flexibility in T-cell responses to some subunit vaccines. These vaccines may induce Th2-type immunity during primary immunization yet promote Th1-dependent responses during later infection. This suggests that designing Th1-inducing subunit vaccines may not always be necessary since this can occur naturally during subsequent infection.     

Relationship between changes in pulmonary kinetics and autonomic regulation of blood flow

Various regulatory mechanisms of pulmonary oxygen uptake () kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and kinetics. Forty‐nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate‐ and heavy‐intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of , cardiac output () and RMSSDRR were determined using a mono‐exponential model. During heavy‐intensity exercise, the phase II τ of was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating kinetics during heavy‐, but not moderate‐, intensity exercise.     

The readability of pediatric patient education materials on the World Wide Web.

BACKGROUND: Literacy is a national and international problem. Studies have shown the readability of adult and pediatric patient education materials to be too high for average adults. Materials should be written at the 8th-grade level or lower. OBJECTIVE: To determine the general readability of pediatric patient education materials designed for adults on the World Wide Web (WWW). MATERIALS AND METHODS: GeneralPediatrics.com (http://www.generalpediatrics.com) is a digital library serving the medical information needs of pediatric health care providers, patients, and families. Documents from 100 different authoritative Web sites designed for laypersons were evaluated using a built-in computer software readability formula (Flesch Reading Ease and Flesch-Kincaid reading levels) and hand calculation methods (Fry Formula and SMOG methods). Analysis of variance and paired t tests determined significance. RESULTS: Eighty-nine documents constituted the final sample; they covered a wide spectrum of pediatric topics. The overall Flesch Reading Ease score was 57.0. The overall mean Fry Formula was 12.0 (12th grade, 0 months of schooling) and SMOG was 12.2. The overall Flesch-Kincaid grade level was significantly lower (P<.0001), at a mean of 7.1, when compared with the other 2 methods. All author and institution groups had an average reading level above 10.6 by the Fry Formula and SMOG methods. CONCLUSIONS: Pediatric patient education materials on the WWW are not written at an appropriate reading level for the average adult. We propose that a practical reading level and how it was determined be included on all patient education materials on the WWW for general guidance in material selection. We discuss suggestions for improved readability of patient education materials.     

Effects of misalignment on static torsional strength of anterior cervical plate systems

Background contextThere is little understanding of cervical plate misalignment as a risk factor for plate failure at the plate-screw-bone interface.PurposeTo assess the torsional strength and mode of failure of cervical plates misaligned relative to the midsagittal vertical axis.Study designPlastic and foam model spine segments were tested using static compression and torsion to assess effects of misaligned and various lengths anterior cervical plate (ACPs).MethodsDifferent length ACPs and cancellous fixed angle screws underwent axial torsional testing on a servo-hydraulic test frame at a rate of 0.5°/s. A construct consisted of one ACP, four screws, one ultrahigh–molecular weight polyethylene inferior block, and one polyurethane foam superior block. Group 1 had ACPs aligned in the midsagittal vertical axis, group 2 plates were positioned 20° offset from the midline, and group 3 had the ACP shifted 5 mm away and 20° offset from midline. Torques versus angle data were recorded. The failure criterion was the first sign of pullout determined visually and graphically.ResultsGroup 1 had a more direct screw pullout during failure. For the misaligned plates, failure was a combination of the screws elongating the holes and shear forces acting between the plate and block. The misaligned plates needed more torque to failure. The failure torque was 50% reduced for the longer versus the shorter plates in the neutral position. Graphically shown initial screw slippage inside the block preceded visual identification of slippage in some cases.ConclusionsWe observed different failure mechanisms for neutral versus misaligned plates. Clinically, misalignment may have the benefit of needing more torque to fail. Misalignment was a risk factor for failure of the screw-bone interface, especially in longer plate constructs. These comparisons of angulations may be a solid platform for expansion toward a more applicable in vivo model.