Grip strength measurements at two different wrist extension positions in chronic lateral epicondylitis-comparison of involved vs. uninvolved side in athletes and non athletes: a case-control study

Abstract Background Lateral epicondylitis is a common sports injury of the elbow caused due to altered muscle activation during repetitive wrist extension in many athletic and non-athletic endeavours. The amount of muscle activity and timing of contraction eventually is directly dependent upon joint position during the activity. The purpose of our study was to compare the grip strength in athletes with lateral epicondylalgia in two different wrist extension positions and compare them between involved and uninvolved sides of athletes and non-athletes. Methods An assessor-blinded case-control study of eight athletes and twenty-two non-athletes was done. The grip strength was measured using JAMAR® hand dynamometer in kilograms-force at 15 degrees (slightly extended) and 35 degrees (moderately extended) wrist extension positions (maintained by wrist splints) on both involved and uninvolved sides of athletes and non-athletes with unilateral lateral epicondylitis of atleast 3 months duration. Their pain was to be elicited with local tenderness and two of three tests being positive- Cozen's, Mill's manoeuvre, resisted middle finger extension tests. For comparisons of grip strength, Wilcoxon signed rank test was used for within-group comparison (between 15 and 35 degrees wrist extension positions) and Mann-Whitney U test was used for between-group (athletes vs. non-athletes) comparisons at 95% confidence interval and were done using SPSS 11.5 for Windows. Results Statistically significant greater grip strength was found in 15 degrees (27.75 ± 4.2 kgms in athletes; 16.45 ± 4.2 kgms in non-athletes) wrist extension than at 35 degrees (25.25 ± 3.53 kgm in athletes and 14.18 ± 3.53 kgm in non-athletes). The athletes had greater grip strength than non-athletes in each of test positions (11.3 kgm at 15 degrees and 11.07 kgm at 35 degrees) measured. There was also a significant difference between involved and uninvolved sides' grip strength at both wrist positions (4.44 ± .95 kgm at 15 degrees and 4.44 ± .86 kgm in 35 degrees) which was significant (p Conclusion The grip strength was greater in 15 degrees wrist extension position and this position could then be used in athletes with lateral epicondylalgia for grip strength assessment and designing wrist splint in this population.</p

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice

Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications

A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis

Background: Cystic fibrosis (CF) is a chronic, life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene leading to abnormal airway surface ion transport, chronic lung infections, inflammation and eventual respiratory failure. With the exception of the small-molecule potentiator, ivacaftor (Kalydeco®, Vertex Pharmaceuticals, Boston, MA, USA), which is suitable for a small proportion of patients, there are no licensed therapies targeting the basic defect. The UK Cystic Fibrosis Gene Therapy Consortium has taken a cationic lipid-mediated CFTR gene therapy formulation through preclinical and clinical development. Objective: To determine clinical efficacy of the formulation delivered to the airways over a period of 1 year in patients with CF. Design: This was a randomised, double-blind, placebo-controlled Phase IIb trial of the CFTR gene–liposome complex pGM169/GL67A. Randomisation was performed via InForm™ version 4.6 (Phase Forward Incorporated, Oracle, CA, USA) and was 1 : 1, except for patients in the mechanistic subgroups (2 : 1). Allocation was blinded by masking nebuliser chambers. Settings: Data were collected in the clinical and scientific sites and entered onto a trial-specific InForm, version 4.6 database. Participants: Patients with CF aged ≥ 12 years with forced expiratory volume in the first second (FEV1) between 50% and 90% predicted and any combination of CFTR mutations. The per-protocol group (≥ 9 doses) consisted of 54 patients receiving placebo (62 randomised) and 62 patients receiving gene therapy (78 randomised). Interventions: Subjects received 5 ml of nebulised pGM169/G67A (active) or 0.9% saline (placebo) at 28 (±5)-day intervals over 1 year. Main outcome measures: The primary end point was the relative change in percentage predicted FEV1 over the 12-month period. A number of secondary clinical outcomes were assessed alongside safety measures: other spirometric values; lung clearance index (LCI) assessed by multibreath washout; structural disease on computed tomography (CT) scan; the Cystic Fibrosis Questionnaire – Revised (CFQ-R), a validated quality-of-life questionnaire; exercise capacity and monitoring; systemic and sputum inflammatory markers; and adverse events (AEs). A mechanistic study was performed in a subgroup in whom transgene deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) was measured alongside nasal and lower airway potential difference. Results: There was a significant (p = 0.046) treatment effect (TE) of 3.7% [95% confidence interval (CI) 0.1% to 7.3%] in the primary end point at 12 months and in secondary end points, including forced vital capacity (FVC) (p = 0.031) and CT gas trapping (p = 0.048). Other outcomes, although not reaching statistical significance, favoured active treatment. Effects were noted by 1 month and were irrespective of sex, age or CFTR mutation class. Subjects with a more severe baseline FEV1 had a FEV1 TE of 6.4% (95% CI 0.8% to 12.1%) and greater changes in many other secondary outcomes. However, the more mildly affected group also demonstrated benefits, particularly in small airway disease markers such as LCI. The active group showed a significantly (p = 0.032) greater bronchial chloride secretory response. No difference in treatment-attributable AEs was seen between the placebo and active groups. Conclusions: Monthly application of the pGM169/GL67A gene therapy formulation was associated with an improvement in lung function, other clinically relevant parameters and bronchial CFTR function, compared with placebo. Limitations: Although encouraging, the improvement in FEV1 was modest and was not accompanied by detectable improvement in patients’ quality of life. Future work: Future work will focus on attempts to increase efficacy by increasing dose or frequency, the coadministration of a CFTR potentiator, or the use of modified viral vectors capable of repeated administration. Trial registration: ClinicalTrials.gov NCT01621867. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research partnership