B N , J A C , A M , R J ) This trial was registered at clinicalt

B.N., J.A.C., A.M., R.J.). This trial was registered at clinicaltrials.gov under number: NCT01487629. The authors would like to thank Prof Dr Klaus

Dietz, professor emeritus of Medical Biometry (University of Tübingen–Germany), for review of and constructive comments on the statistical analysis. “
“Mayer WJ, Mayer WJ, Klaproth OK, Hengerer FH, Kohnen T. Impact of Crystalline Lens Opacification on Effective Phacoemulsification Time in Femtosecond Laser-Assisted Cataract Surgery. Am J Ophthalmol 2014;157(2):426–432. In the February PD0325901 2014 issue, an error occurred in the first sentence of the “Methods” section: “One hundred fifty eyes of 68 patients with senile cataract were enrolled in this retrospective, nonrandomized cases series between September 2012 and May 2013,” 68 patients should have been revised to 86 patients. The correct number is also written in the abstract. The authors regret this error. “
“Charbel Issa P, Finger RP, Kruse K, Baumüller S, Scholl HPN, and Holz FG. Monthly Ranibizumab for Nonproliferative Macular Telangiectasia Type 2: A 12-Month Prospective Study. Am J Ophthalmol 2011; this website 151(5): 876-886. In the May 2011 issue of the American Journal of Ophthalmology,

an error is reported in the above article. Towards the end of the last paragraph of the article, the text reads, “While the unchanged distance visual acuity at the 12 month follow-up would have suggested a stable disease course, microperimetry revealed a progressive paracentral loss of retinal light sensitivity (study eye: −2.3dB; SD 2.4; p= Rutecarpine 0.01; fellow eye: 1.3dB; SD 1.6; p = 0.03; assessed were 9 testing points covering an area of 3×3 degrees temporal to the

foveal center) due to continuing photoreceptor degeneration.”30 The value for “fellow eye” in the above paragraph incorrectly appears as “1.3dB.” The correct value is “−1.3db. The authors regret this error. “
“The 3rd World Congress on Controversies in Ophthalmology (COPHy), March 22–25, 2012, Istanbul. Website: http://www.comtecmed.com/COPHy/2012/ COPHy Istanbul will be devoted to evidence-based debates and discussions amongst chairpersons, speakers and the audience, all of whom will examine and analyze the most relevant issues raised during the course of 2011 within the field of Ophthalmology. Simultaneous sessions will emphasize controversies within anterior segment, retina, and glaucoma. “
“Figure options Download full-size image Download high-quality image (251 K) Download as PowerPoint slide Dr Alberto Urrets-Zavalía Jr, who passed away on July 31, 2010, at the age of 89, was one of the most influential Argentine ophthalmologists of the 20th century. Born in Córdoba (Argentina) on September 30, 1920, he was the son of a nationally renowned ophthalmologist and the eldest of 6 children. In 1953, he founded in Córdoba the Cornea and Glaucoma Surgical Center.

In conclusion, the study indicated that FMDV could be transmitted

In conclusion, the study indicated that FMDV could be transmitted from infected buffalo to susceptible in-contact naïve buffalo and cattle by direct contact. FMD vaccination of buffalo could reduce the transmission of disease by reducing virus replication, but for completely blocking the transmission of FMDV, higher Selleckchem BMN673 doses of antigen payload might be required in the vaccine formulation. The study highlights the potential role of Indian buffalo in FMDV transmission,

and this is something that may have an impact on future control strategy. This work was supported by FP7 DISCONVAC grant 2009-226556. Thanks are also due to R. Kumar, J. Anil kumar and K. Manikumar for their help in carrying out the animal experiments. SP and DJP are Jenner Investigators. “
“To date, an effective vaccine for HIV has

yet to be realized [1]. Selleck RAD001 Here, we consider vaccines that fight the virus by inducing responses from cytotoxic T lymphocytes (CTLs). One key roadblock to an effective vaccine is that CTL-mediated attack of HIV infected cells is temporarily effective, but only until HIV mutates to escape such attack. Research has suggested that the HIV virus remains fit despite mutations within or near most CTL epitopes, and that escape at only a relatively small number of these locations will result in a less fit virus [2], [3] and [4]. Consequently, it has been proposed that a successful vaccine would elicit responses exclusively against epitopes that are resistant to mutation or are otherwise characterized by a superior immune response [2], [3], [4], [5], [6], [7], [8], [9], [10] and [11]. Note that the need to elicit responses to multiple second epitopes in a single individual may be important for effective viral control [2], [3], [4], [5], [6], [7], [8], [9], [10] and [11]. Unfortunately, CTL epitopes, like other small peptides, do not readily produce an immune response when injected on their own, even when combined with toll-like-receptor (TLR) agonist adjuvants known to boost the

immune response to administered antigens [12]. Here, we describe a vaccine delivery mechanism that can elicit interferon gamma ELISPOT responses to multiple specific CTL epitopes. The delivery mechanism is a synthetic, non-living vector consisting of large d,l poly(lactic-co-glycolic) acid (PLGA) microspheres that carry multiple specific CTL epitopes. While PLGA microspheres have been investigated previously (see, e.g., [13] and [14] and references therein), we improve on this delivery mechanism in several respects. First, we demonstrate the need to include adjuvants positioned both inside and outside the microspheres, in contrast to previous work [13]. Second, we demonstrate in mice that it can be used to elicit substantial CTL responses to more than one epitope in the same individual, whereas previous studies have investigated only the inclusion of a single epitope.

The synthesized

compounds were evaluated for the obeyance

The synthesized

compounds were evaluated for the obeyance of Lipinski parameters (RO5), topological polar surface area (TPSA), molar volume (MV), number of rotatable bonds (RB), absorption percentage (% ABS) and drug score.16 and 17 A series of N,5-disubstituted-1,3-thiazolidine-2,4-dione derivatives (3a–h, 4a–h) were designed and synthesized according to Scheme 1. The starting compound 1,3-thiazolidine-2,4-dione (1) and the N-substituted-1,3-thiazolidine-2,4-diones (2a, 2b) were prepared by literature method with modification.18 and 19 The compounds 2a, 2b were prepared by the reaction of methoxy phenacyl bromide/substituted benzyl halide with 1,3-thiazolidine-2,4-dione in ethanolic GDC0449 KOH. The initial potassium salt formation was ensured by the drop wise addition of KOH solution to the ethanolic thiazolidine-2,4-dione (1) and stirring at rt for 15 min, which on subsequent addition of methoxy phenacyl bromide/p-nitro benzyl bromide afforded N-substituted-1,3-thiazolidine-2,4-dione analogues (2a, 2b). The TLC support for qualitative analysis was utilized and the reaction was found completed after 6 h of reflux with stirring. The pure compounds were isolated by column chromatography. Modifications in the reaction conditions such as performing a single step reaction for the formation of potassium salt and the Perifosine subsequent N-alkylation rather than in two steps and controlled stirring before and after the addition of alkyl halide, influences the reaction

time and drastically decreased it to 6 h when compared with the literature method. 20 Further synthetic investigation as mentioned in Scheme 1 is performed with N-substituted-1,3-thiazolidine-2,4-diones (2a, 2b). Knoevenagel condensation of various aromatic aldehydes with N-sustituted-1,3-thiazolidine-2,4-diones afforded sixteen

N,5-disubstituted-1,3-thiazolidine-2,4-diones (3a–h and 4a–h). The carbanion formation, prerequisite for the knoevenagel condensation reaction is ensured by the use of piperidine as base, while removal of water is ensured by Dean–Stark apparatus.20 The compounds 4d, 4a, 3b and 3e were obtained with 92%, 87%, 85% and 83% yield (Table 1). The structures of the synthesized compounds were established based on spectral data analysis. The following observations are few among them: Aromatic CH stretching vibrations at 2841–3120 cm−1, the two ketones of the dione system were observed at 1602–1775 cm−1 these in the IR spectrum, appearance of –OH protons at δ 8.9–9.3, aromatic protons at δ 7.05–8.4, benzylidene ( CH) protons at δ 7.78–8.1, methoxy (–OCH3) protons at δ 3.54–3.83 and methyl (–CH3) protons at 2.9–3.0 in 1H NMR spectrum of the synthesized compounds. The absence of characteristic –NH peak of 1,3-thiazolidine-2,4-dione at 3200 cm−1 in IR spectra and a signal at δ 12 in 1H NMR confirmed the N-alkylation of 1,3-thiazolidine-2,4-dione. It was further evidenced by the appearance of molecular ion peak at m/z 265 and m/z 252 for compounds 2b and 2c respectively.

org au “
“Worldwide, breast cancer remains the most commonly

org.au “
“Worldwide, breast cancer remains the most commonly diagnosed cancer in women.1 Due to advancements in treatment approaches for breast cancer, the 5-year survival rate has improved dramatically, and in Canada is approximately 88%.2 Despite the efficacy of treatment in improving survival, women who have undergone treatment for breast cancer face both acute and chronic impairments in various aspects of physical function as a result of their treatment, which may involve a combination of surgery, chemotherapy, radiation therapy, hormonal therapy or other targeted biological therapies.3 Physiotherapists have the potential to play selleck inhibitor an important role in cancer care by identifying

and monitoring changes

in physical function during and following breast cancer treatment, and by prescribing interventions to address deficits in physical function. For the purposes of the present review, three main aspects of physical function have been selected: aerobic capacity, muscular fitness of the upper and lower extremities, and mobility. These aspects of physical function were selected because selleckchem they represent clinically relevant areas of focus for physical therapists, they are commonly assessed in exercise oncology literature, and each has established objective outcome measures available for comparison. Declines in aerobic capacity have been observed during breast cancer treatment, which is likely a combination of the direct and indirect effects of the treatment itself, and associated reduction in physical activity leading to deconditioning.4 Maximal oxygen consumption (VO2max) – the upper all limit to the rate of oxygen utilisation, as measured by a cardiopulmonary exercise test – is the gold standard measurement of cardiorespiratory fitness and the capacity for physical work.5 In clinical populations, VO2max may not be achieved during a cardiopulmonary exercise test, so the peak oxygen consumption (VO2peak)

is used instead. VO2peak is associated with all-cause,6 cardiovascular disease-specific7 and 8 and breast cancer-specific9 mortality. A recent cross-sectional study reported that women diagnosed with breast cancer have a VO2peak on average 27% lower than that expected for healthy sedentary women.10 Although VO2peak has a strong association with health outcomes, cardiopulmonary exercise testing requires expensive, specialised equipment and medical supervision for high-risk individuals, thereby limiting its feasibility. A submaximal exercise test, such as a progressive exercise test that is terminated at 85% of age-predicted maximal heart rate or 70% of heart rate reserve, is often a more feasible alternative in clinical practice because it poses less risk and can be done without collection of expired metabolic gases. VO2max can be estimated with a submaximal exercise test.

Taken together,

cordycepin may be a potential candidate a

Taken together,

cordycepin may be a potential candidate antimetastatic agent through inhibiting the activity of MMPs and accelerating the release of TIMPs from cancer cells. In in vivo studies, Yoshikawa et al. investigated whether platelet aggregation accelerates hematogenous metastasis of B16-F1 mouse melanoma (B16-F1) see more cells in C57BL/6Cr mice and the effect of cordycepin on hematogenous metastasis accelerated by ADP. ADP significantly increased the number of metastatic lung nodules in mice injected intravenously with B16-F1 cells in a dose-dependent manner, and cordycepin significantly reduced the number of metastatic nodules of B16-F1 cells formed in the lung accelerated by ADP injected simultaneously with B16-F1 cells (17). Accordingly, ADP accelerated hematogenous metastasis and cordycepin had an inhibitory action on hematogenous metastasis of B16-F1 cells via the blocking of ADP-induced S3I-201 purchase platelet aggregation in vivo. In in vivo studies, Sprague-Dawley rats received a single i.v. injection of a colloidal carbon solution, and then the clearance rate from the blood was measured. The rats had been administered WECS p.o. daily at a dose of 200 mg/kg for twenty-five days

until the day before the injection of colloidal carbon. The half-life of the colloidal carbon in the blood of rats administered WECS at 200 mg/kg was significantly shorter than that of the control rats (18). These results indicate that orally administered WECS activates one of the immune systems in rats. In in vitro studies, Yamaguchi et al. indicated that WECS

exhibited potent antioxidant and antilipid peroxidation activities and inhibited the accumulation of cholesteryl ester in macrophages via the suppression of low-density lipoprotein (LDL) oxidation (19). Furthermore, Yamaguchi et al. showed that WECS administered orally prevented cholesterol deposition in the aorta of atherosclerotic ICR mice by the inhibition of LDL oxidation mediated Florfenicol by free radicals rather than by reduction of the serum lipid level (20). Guo et al. reported that cordycepin administered i.g. at 25 and 50 mg/kg for two weeks prevented hyperlipidemia in Syrian golden hamsters fed a high-fat diet via the activation of AMP-activated protein kinase (AMPK) (21). In addition, Won et al. demonstrated that cordycepin injected orally at 10 mg/kg for 14 days attenuated neointimal formation by inhibiting reactive oxygen species-mediated responses in vascular smooth muscle cells in Sprague-Dawley rats (22). Accordingly, cordycepin, as an active ingredient of WECS, may exert beneficial effects on the formation of atherosclerotic lesions induced by oxidative stress.

26 Decreased range of neck movement is inconsistent in that some

26 Decreased range of neck movement is inconsistent in that some selleckchem studies have found it to be predictive and others have not.15 This is not to say that these factors should not be considered in the clinical assessment of patients with WAD, but they should not be used to gauge prognosis. Other factors commonly considered to predict outcome, such as those associated with compensation processes and accident-related factors, are not robust prognostic indicators.27 Similarly, demographic or social factors such as age, income and educational levels

demonstrate inconsistent prognostic capacity.2 and 15 Most prognostic studies of WAD have been phase 1 or exploratory studies, with few confirmatory or validation studies having been conducted.28 Validation studies are important in order

to confirm the prognostic capacity of identified selleck products factors in a new and independent cohort. A recent study undertook validation of a set of prognostic indicators including initial disability, cold hyperalgesia, age and post-traumatic stress symptoms. The results indicated that the set showed good accuracy (area under the curve 0.89, 95% CI 0.84 to 0.94) in discriminating patients with moderate/severe disability from patients with full recovery or residual milder symptoms at 12 months post-injury.16 These results are clinically useful, as physiotherapists usually aim to broadly identify patients likely to report persistent moderate to severe symptoms. Such a validation study is rare in this area of research and goes some way towards providing greater confidence for the use of these measures in the early assessment of whiplash injury. Based on the results of previous cohort studies, a clinical prediction rule to identify both chronic moderate/severe disability and full recovery at 12 months post-injury was recently developed. The results indicated that an initial Neck Disability

Index score of ≥40%, age ≥35 years, and a score of ≥6 on the hyperarousal subscale of the Posttraumatic Stress Diagnostic Scale29 could predict patients with moderate/severe disability at 12 months with fair sensitivity (43%, Sitaxentan 95% CI 31 to 55), good specificity (94%, 95% CI 89 to 96), and a positive predictive value of 71% (95% CI 55 to 84).30 It is also important to predict patients who will recover well as these patients will likely require less intensive intervention. Initial Neck Disability Index scores of ≤32% and age ≤35 years predicted full recovery at 12 months post-injury, with a positive predictive value of 71%.30 A third medium-risk group could either recover or develop chronic pain and disability (>32% on the Neck Disability Index, score >3 on the hyperarousal subscale). The hyperarousal subscale comprises five items that evaluate the frequency of symptoms including: having trouble falling asleep, feelings of irritability, difficulty concentrating, being overly alert, and being easily startled.

, 1967) The relationship between early life stress exposure and

, 1967). The relationship between early life stress exposure and subsequent resilience in both primates and rodents follows click here the abovementioned U-shaped curve. Prolonged maternal separation and social isolation in infant rhesus monkeys produce an increased stress response and “despair-like” behavior in subsequent social separation tests (Young et al., 1973). Rats exposed to moderate early life stress show enhanced measures of resilience compared to both severely and minimally stressed rats (Macri and Wurbel, 2007). For example, early postnatal rats exposed to brief daily handling (a moderate stressor) subsequently show attenuated stress response compared to undisturbed pups and pups

exposed to prolonged daily maternal separation (a more severe stressor) (Plotsky and Meaney, 1993 and Macri et al., 2004). Chronic unpredictable stress (CUS) is a useful model for examining stress vulnerability and resilience in rodents (Ricon et al., 2012 and LaPlant et al., 2009). In CUS paradigms, animals are exposed to varying mild stressors sequentially for a period of 1–7 weeks (Krishnan and Nestler, 2011 and Willner, 1997).

Stressors can include mild foot shock, physical restraint, tail suspension, light/dark cycle disruption, food or water restriction, changes to cage mate, etc., and are changed after several hours to minimize habituation (LaPlant et al., 2009 and Willner, 1997). CUS produces a range of depression and anxiety-like behaviors in rodents including Epacadostat order enough anhedonia, measured as decreased sucrose preference, despair-like behavior, measured as increased immobility in the forced swim and tail suspension tests, and novelty suppressed feeding, measured as a decrease in approach to a

novel food item (Krishnan and Nestler, 2011, Mineur et al., 2006 and Feng et al., 2012). Mice exposed to CUS also display decreased grooming, aggression, and sexual behaviors. Certain CUS-induced behavioral changes, such as novelty suppressed feeding, can be reversed only by chronic antidepressant treatment (Willner, 1997), making CUS relevant to human antidepressant responses. Female mice display immobility in the forced swim test after just 6 days of subchronic unpredictable stress (SCUS) whereas males are generally resilient to SCUS and require 20–28 days of CUS exposure to elicit depression- and anxiety-like behavior (Hodes, G.E. et al., Soc. Neurosci. Abstr. 219.01, 2011). Interestingly, age is a factor in response to CUS—male rats exposed to 60 days of CUS in the juvenile period exhibit greater memory retention in a two-way shuttle avoidance task compared to rats exposed to the same stressor in adulthood, indicating enhanced cognitive resilience ( Ricon et al., 2012). Sex differences and age effects in susceptibility to CUS-induced depression and anxiety-like behavior make this a powerful tool for investigating the hormonal and neural basis for stress vulnerability and resilience across the lifespan.

All three groups showed improvements at 12 weeks; however,

All three groups showed improvements at 12 weeks; however, HKI-272 chemical structure at 6 months only the groups using the eccentric exercises and the heavy slow resistance exercises still showed improved VISA-P and VAS scores. The heavy slow resistance group showed improved tissue normalisation of the collagen and also demonstrated better clinical presentations

than the eccentric group within the 12-week follow-up. Combined exercises with eccentrics, concentrics and plyometric training for the Achilles tendon were studied by Silbernagel and colleagues.49 Athletes were allowed to continue training in their sports during the first 6 weeks of rehabilitation, as long as their pain did not go over 5/10 on the VAS during activity and returned to normal by the next morning.49 While this study was investigating Achilles tendinopathy, this combined approach is often used clinically with patellar tendinopathy and should be considered as a treatment option. Functional strengthening must address high-load tendon capacity as well as kinetic chain deficits and movement patterns. Once these patterns have improved, the athlete should begin

sports-specific training. Faster contractions can progress loads towards the stretch-shorten cycle that forms the basis for return to sports. Early drills should include: skipping, jumping and hopping, progressing to agility tasks, direction changes, learn more sprinting and bounding movements. It is important to quantify these tasks and use a high-low-medium-load day approach in early reintroduction of high-load activities and return to sports. Also, include training specificity Terminal deoxynucleotidyl transferase when returning an athlete back to their sport, including movement assessment for optimal kinetic chain loading. Other techniques may be useful in augmenting an exercise program; however, there is little evidence for effect of passive treatments for patellar tendinopathy. Exercise, pulsed ultrasound and transverse friction massages have been compared, and exercise had the best effects in the short and long term.50 Manual therapy

techniques, including myofascial manipulation of the knee extensor muscle group, have had a positive effect on reducing pain in patellar tendinopathy patients in short-term and long-term follow-up.51 Other passive therapies, including braces and taping techniques, are often used clinically to help unload the patellar tendon, however, no evidence supports their efficacy. Passive therapies are best used to reduce symptoms in season so the athlete can continue to participate in rehabilitation and sport. Extracorporeal shockwave therapy, corticosteroid injections, platelet-rich plasma and other injections are interventions frequently used in the clinical setting, yet have limited evidence supporting their use in patellar tendinopathy. There was no benefit of extracorporeal shockwave therapy compared to placebo for in-season athletes with chronic patellar tendinopathy.

Eugenol (99%, C10H12O2) was obtained from Aldrich, USA Commercia

Eugenol (99%, C10H12O2) was obtained from Aldrich, USA. Commercial Ayurvedic formulations (plants) like Caturjata (tvak, ela, patra, kesera), 20Sitopaladi Churna (Cinnamomum verum zeylanicum-pippali, ela, tvak), 20Lavangadi Vati (lavanga, marica, aksaphala, khadirasara, babbula), 20Jatiphaladi Churna (Cannabis sativa-jatiphala, lavanga, ela, JAK phosphorylation patra, tvak, nagakesara, candana, tila, tvaksiri, tagara, amla, talisa, pippali, pathya, sthulajiraka), 20and clove oil (Syzygium aromaticum)

20 containing eugenol were purchased from local markets. HPLC grade methanol was procured from Merck Specialist Private Limited (Mumbai, India). Distilled water was prepared in-house using Millipore (Millipore S.A. Molsheim, France). All other chemicals used were of analytical grade. A stock solution of 1000 ppm was prepared by accurately weighing 10 mg of eugenol standard in a 10 mL volumetric flask and it was further diluted with HPLC grade methanol up to the mark. The GDC-0199 cell line solution was vortexed for 10 s. 1 g of ayurvedic formulations were taken in 10 mL of methnol and then solvent extraction was performed using a rotary shaker for 24 h. The tubes were centrifuged at 4000 rpm for 10 min and the solution was filtered with Whatman filter paper no. 41. The filtrate was collected in polypropylene tubes and stored at 4 °C until further analysis.

Furthermore, the filtrate was given appropriate dilution in mobile phase prior to injection on to the HPLC system. The HPLC system used for quantification of eugenol consisted of a Jasco PU-980 pump, AS-2057 auto sampler and Jasco UV-970 detector. The chromatogram peaks were quantified by means of PC based Borwin software (Version 1.5). Chromatography separation for analyte was achieved on cosmosil C18 analytical column (150 mm × 4.6 mm, 5 μ) maintained at ambient temperature. The mobile phase Ketanserin was pumped at a flow rate of

1 mL/min. The mobile phase was filtered through a 0.45 μ nylon membrane filter and degassed in an ultrasonic bath prior to use. The injection volume was 30 μL, the flow rate was 1.0 mL/min and a chromatographic peak was detected at 215 nm. The entire experimental analysis was according to the ICH guidelines and was validated for calibration curve, limit of detection, limit of quantification, system suitability, precision, accuracy, solution stability and ruggedness.21 Marketed commercial formulation samples of Caturjata Churna, Lavangadi Vati, Sitopaladi Churna, Jatiphaladi Churna and clove oil were accurately weighed in weighing balance. Later they were transferred to Tarson tubes, filled with methanol and kept overnight on rotator shaker. These tubes were subsequently centrifuged, filtered and stored in fridge for further HPLC analysis.

Results: 400 participants completed the study; 219 potential part

Results: 400 participants completed the study; 219 potential participants were excluded because they were assessed as having a low risk from the biomechanical

plantar pressure assessment. After 7 weeks training, there were 21 injuries in the intervention (orthosis) group and 61 injuries in the control group resulting in an absolute risk reduction of 0.20 (95% CI 0.10 to 0.28) and a number needed to treat of 5 (95% CI 4 to 8). A similar number of minor adverse events of foot blisters were reported by both groups (intervention n = 12, control n = 16) Conclusion: The use of customised foot orthoses during military training for those assessed as being at-risk resulted GSK1210151A chemical structure in a 20% reduction in lower limb overuse injury rate. [Absolute risk reduction, number needed to treat and 95% CIs re-calculated by the CAP Co-ordinator.] A recent Cochrane systematic review found that foot orthoses are effective for the treatment of foot pain ( Hawke et al 2008). The question of whether orthoses are effective for the prevention of injuries has also received investigation, including two systematic reviews

learn more ( Collins et al 2007, Landorf & Keenan 2007). Both reviews found that orthoses prevent injuries in certain populations (mainly military recruits). Whether the orthoses used are prefabricated or customised does not appear to matter ( Collins et al 2007, Landorf & Keenan 2007). What does matter is that they until are appropriately contoured to the foot and they are not just shock-absorbing insoles, which do not prevent injury ( Landorf & Keenan 2007). Although this is not the first randomised trial to identify a positive preventive role of orthoses – as Franklyn-Miller

and colleagues claim – it adds to the evidence base that appropriately contoured foot orthoses are beneficial for preventing injuries. It is generally well conducted; however it does have some limitations, some of which were acknowledged by the authors. This trial would have been strengthened with a control group that received some form of sham treatment. It also appears that the authors may have overestimated the treatment effect with their calculation of the absolute risk reduction, although the re-calculated absolute risk reduction and number needed to treat presented in the synopsis still suggests that the intervention was very beneficial. A final issue, and one that is arguably more important, is whether a cheaper prefabricated orthosis could provide similar benefit compared to the semi-customised orthosis used in this trial. The prescription technique, while novel, is not commonly used in clinical practice, raising an issue about generalisability of the findings and whether more mass-produced and, as a consequence, cheaper orthoses may be as effective or better. A similar trial found a simpler orthosis to be effective for preventing shin splints (Larsen and Keenan 2002).