This coincides with the results obtained in our laboratory for DNA extraction and analysis using agarose gel electrophoresis, where the MOLT-4 and HL-60 line cells treated with lectins ConA and ConBr showed the pattern of a DNA “ladder” characteristic of apoptosis (data not shown). The literature has shown that the lectin ConA induces apoptosis of mice macrophages PU5–1.8, DNA fragmentation by agarose gel electrophoresis at 25 μg/ml, and liberation of cytochrome-c ( Suen

et al., 2000). A375 human melanoma cells treated with ConA at 25 μg/ml showed a considerable increase in sub-G1 cells with hypodiploid content, click here which is characteristic of apoptotic cell death ( Liu et al., 2009c). Our results indicate that lectins ConA and ConBr promoted mitochondrial depolarization in a concentration-dependent manner with MOLT-4 cells from 5 μg/ml (p < 0.001). The lectin ConA produced a greater depolarization than ConBr ( Fig. 5A). These

results are confirmed by data from Kulkarni et al. (1998), which shows that ConA (50 g/ml) induces apoptosis in FGH human fibroblast cells and is associated with a decrease in transmembrane potential, reduced intracellular calcium levels, and decreased expression of Bcl-2, a protein involved with cell death protection. Another report shows that treatment with ConA on A375 melanoma cells resulted in the induction of mitochondrial dysfunction due to an increased depolarization, release of cytochrome c, and increased activity of caspases Pexidartinib ic50 -8, -9, and -3, which are all characteristic of apoptosis ( Liu et al., 2009c). The generation of ROS from mitochondria and other intracellular sources can cause serious damage to fundamental cellular molecules such as lipids, proteins and DNA. In addition, chemical agents that induce cytotoxicity have been implicated in the production of ROS. Indeed, Resminostat ROS is known to be involved in the early stages of apoptosis and induces mitochondrial membrane

depolarization (Ravidran et al., 2011). In this paper we demonstrated that ConBr and ConA lectins provoked apoptosis on MOLT-4 and HL-60 cells and this action also showed an increase of ROS levels. However the production of these radicals was significant only at the highest concentration tested (50 μg/mL, p < 0.001) suggesting that ROS production stimulated by lectins is not the initial factor inducing apoptosis, since the cellular damage and apoptotic events induced by ConA and ConBr might already be observed from the lowest concentration of lectins tested (5 μg/mL). It is reported in the literature that apoptosis is the main mechanism of cell death caused by lectins (Oliveira et al., 2011 and Li et al., 2011). The lectin from rice bran induced chromatin condensation, phosphatidylserine externalization, the formation of a DNA “ladder” in human monoblastic leukemia U937 cells, and apoptosis with cell cycle arrest.

, 2011). Several studies have demonstrated that astaxanthin exhibits a wide variety of biological

activities, including the prevention and treatment of various diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, and neurodegenerative diseases (Chew et al., 1999, Jyonouchi et al., 2000, Kishimoto et al., 2010, Marin et al., 2011, Naguib, 2000 and Otton Nutlin-3a supplier et al., 2011). The presence of the hydroxyl and keto moieties on each ionone ring (Fig. 1) explains some of its unique features such as the ability to be esterified, a higher antioxidant activity, and a more polar nature than Target Selective Inhibitor Library chemical structure other carotenoids (Hussein et al., 2006). Astaxanthin may act as a strong antioxidant by donating the electrons and reacting with free radicals to convert them into more stable products and terminate free radical chain reaction in a wide variety of living organisms. The nonpolar middle segment of the astaxanthin

molecule is a series of carbon-carbon double bonds, which alternate with carbon-carbon single bonds, termed “conjugated”. This polar-nonpolar-polar layout also allows the astaxanthin molecule to take a transmembrane orientation, making a precise fit into the polar-nonpolar-polar span of the cell membrane (Kidd, 2011). As mentioned by many authors, the antioxidant activity of astaxanthin appears to be greater than that of beta-carotene and alpha-tocopherol (Fukuzawa et al., 1998 and Naguib, 2000). However, studies from our group which evaluated the antioxidant effect of astaxanthin on leukocytes in human and animal models, showed a modest antioxidant action (Bolin et al., 2010, Guerra and Otton, 2011, Macedo et al., 2010, Demeclocycline Mattei et al., 2011, Otton et al., 2010 and Otton et al., 2011), mainly observed in the reduction of superoxide and hydrogen peroxide

production. Vitamin C is an essential micronutrient, which has been implicated in a variety of biological processes, including immune response (Maeng et al., 2009). Vitamin C or l-ascorbic acid is the body’s most important intracellular and extracellular aqueous-phase antioxidant. This antioxidant easily scavengers peroxyl radicals, superoxide anion, singlet oxygen and hypochlorite (Sies and Stahl, 1995). The oxidation of vitamin C by reacting with ROS generates the ascorbyl radical that has little reactivity, crucial to the antioxidant effect of vitamin C. Ascorbic acid is considered a physiological substrate for myeloperoxidase (MPO) and its effect on myeloperoxidase-dependent processes is widely attributed to scavenger or quencher actions on hypochlorous acid (Myzak and Carr, 2002 and Savenkova et al., 1994).

In 2003, a project was initiated to assess reactions to 11 major diseases of maize inbred lines that are used in current breeding programs. The objective of the present study was to evaluate the reactions to NCLB, SCLB, CLS, GLS, common rust, and southern rust of a collection of parental inbred lines that are actively used in most maize breeding programs or are widely CAL-101 mw grown cultivars. One hundred and fifty-two inbred lines of maize were collected from the major maize breeding

programs in China and the seeds were increased at the Maize Centre, Chinese Academy of Agricultural Sciences (CAAS), Beijing, China. Based on information of their pedigrees and genetic structures [19], [20] and [21], 129 inbred lines were categorized into heterotic group A or B. Group A contained subgroups PA (group A germplasm derived from modern U.S. hybrids) (30 lines), BSSS (Iowa Stiff Stalk Synthetic population) (25 lines), and LRC (derivatives of Lvda red cob Chinese landrace) (19 lines); and group B consisted of subgroups PB (group B germplasm derived from modern U.S. hybrids) (18 lines), Lan (Lancaster Surecrop) (17 lines), and SPT (derivatives of Tangshan Sipingtou Chinese landrace) (20 lines). Twenty-three lines were not assigned to any subgroup, owing to a lack of pedigree or molecular

genetic information (Table 1). For accurate evaluation of disease reactions under appropriate environments, the screening nursery was located in disease epidemic areas: the NCLB nursery was in Harbin, Heilongjiang province; SCLB and CLS nurseries were in Beijing; GLS and common rust nurseries were in Shenyang, GKT137831 nmr Liaoning province; and the southern rust nursery was in Sanya, Hainan province in

the winter growing season. The first screen for resistance to NCLB, SCLB, CLS, GLS, and common rust was conducted in 2003 and 2004 for 106 and 46 lines, respectively, and was repeated from 2004 to 2005. Reactions to southern rust were evaluated in 2004 and repeated in 2005. Seeds were planted on the farm of the Heilongjiang Academy of Agricultural Sciences (HAAS), Harbin, Heilongjiang province, China. The inbred lines Mo 17 and Huobai were used as resistant and susceptible controls, respectively. Race 1 of E. turcicum was amplified on sorghum (Sorghum bicolor [L.] Moench) grain medium [22] Racecadotril at 23–25 °C in the dark to promote sporulation. Spores were suspended in distilled water at concentrations of 1 × 105 mL− 1 to 1 × 106 mL− 1 before inoculation. At growth stage V10 [23], inoculation was performed by spraying approximately 10 mL of spore suspension onto the leaf surfaces of each plant. Seeds of each line were grown on the experimental farm of the Institute of Crop Science, CAAS, Beijing, China. Lines Mo 17 and Luo 31 were used as resistant and susceptible controls for assessment of SCLB reactions, and Shen 137 and Huangzaosi were grown as resistant and susceptible controls for evaluation of reactions to CLS.

Our study cohort consisted of all patients treated with RFA for BE who underwent subsequent selleck biopsy.

SSIM was defined as metaplastic columnar tissue found beneath an overlying layer of intact squamous epithelium. We performed a simple bivariate analysis comparing those with and those without SSIM using parametric statistics. We then performed logistic regression analysis including predictor variables associated with SSIM in bivariate analysis (p<0.2). The model was reduced using the likelihood ratio test to determine any independent predictors of SSIM (p<0.05). At least one biopsy session was performed in 4691 of 5530 (85%) patients treated with RFA for BE, among whom 410 (8.7%) were found to have SSIM on at least one occasion on follow-up endoscopic biopsies. Compared to those without subsquamous metaplasia, patients with SSIM were older (64.0 vs. 61.6 years, p<0.0001); more commonly male (79 vs. 73%, p=0.02); had longer BE segments (5.3 vs. 3.9 cm, p<0.0001); more

frequently selleck screening library had advanced neoplasia (high-grade dysplasia, intramucosal carcinoma, invasive cancer) before treatment (35% vs 23%, p<0.001); required more RFA treatment sessions (2.7 vs. 2.3, p<0.0001); and had more biopsy sessions performed (1.7 vs. 1.3, p<0.0001). In our multivariable logistic regression model, SSIM was independently associated with: 1) increased age (OR 1.02 per year, 95% CI 1.01 - 1.03); 2) length of Barrett's (1.08 per cm, 1.05 - 1.11); 3) number of RFA treatment sessions (1.11 per session, 1.05 - 1.17); 4) PPI compliance during treatment (1.47, 1.10 - 1.96); and 5) number of biopsy sessions (1.19 per session; 1.13 - 1.26). Of subjects treated with RFA for BE in a national registry, 8.7% were found to have SSIM at some point on follow-up biopsies. SSIM was independently associated with age, BE length, number of RFA treatment sessions, PPI compliance, and number of biopsy sessions performed. Surveillance biopsies of endoscopically normal mucosa are warranted after RFA, particularly among patients with these risk factors. Novel approaches

to identify sub-squamous disease may have 3-oxoacyl-(acyl-carrier-protein) reductase utility in surveillance of the post-ablation patients, particularly those at high risk for SSIM. Subsquamous metaplasia (n=410) No subsquamous metaplasia (n=4281) p-value Age, yrs 64.0 ± 10.9 61.6 ± 11.3 <0.0001 Caucasian race, % (n) 92% (378) 93% (3996) 0.38 Male gender, % (n) 79% (322) 73% (3137) 0.02 Length of BE segment, cm 5.3 ± 3.7 3.9 ± 3.2 <0.0001 Pre-treatment fundoplication, % (n) 8% (31) 5% (228) 0.058 Advanced neoplasia before treatment (HGD, IMC, EAC), % (n) 35% (142) 24% (1044) <0.001 Treated with EMR before RFA, % (n) 10% (41) 10% (412) 0.81 Total RFA treatments 2.7 ± 1.4 2.3 ± 1.2 <0.0001 Circumferential treatments 0.9 ± 0.8 0.6 ± 0.8 Focal treatments 1.7 ± 1.6 1.3 ± 1.2 Total biopsies performed 1.7 ± 1.6 1.3 ± 1.2 <0.0001 Treatment at an academic medical center, % (n) 33% (134) 29% (1254) 0.

In conclusion, our findings are of vital importance because they

could help avoid the higher susceptibility to develop cancer induced by the immunosuppressive effects of P. aquilinum that were revealed in our previous report ( Caniceiro et al., 2011). Furthermore, selenium supplementation might help prevent some of toxic effects of ptaquiloside in humans who have been exposed directly or indirectly to it in areas infested by bracken fern, where the animal source foods, water and air are likely to contain ptaquiloside. In summary, these results show for the first time that ptaquiloside-induced immunosuppression is associated with increased expression of metallothionein in NK cells and that check details selenium inhibited selleck chemicals llc this alteration. The authors declare that there are no conflicts of interest. This work was supported by the Fundação de Amparo a Pesquisa do Estado

de São Paulo (FAPESP) [07/50313-4 and 10/52186-2 to A.O.L.]. We thank Carolina Aoki and Regina Maki (GE Healthcare, SP, Brazil) for kindly providing the NanoVue™ Plus spectrophotometer. “
“Chronic inhalation of fine and ultrafine particulate matter has been associated with adverse pulmonary effects including fibrosis and cancer, as well as exacerbation of existing conditions such as asthma, bronchitis and chronic obstructive pulmonary disorder (Bonner, 2007 and Knaapen et al., 2004), in addition to cardiovascular disease (Dockery et al., 1993 and Pope et al., 2004). Human exposure to manufactured nanomaterials (NMs), which have at least one size dimension that is less than 100 nm, may constitute an increased risk of adverse effects especially following inhalation exposure, and their potential to induce

toxic effects is poorly understood (Handy and Shaw, 2007). Moreover, the human health risks associated with inhalation exposure have not been adequately MRIP investigated. Methods that can be effective in screening for NM toxicities are paramount, due to the countless variations in physical and chemical properties of NMs in terms of size, shape, agglomeration and surface coatings. Traditional assays used in human health risk assessment (HHRA) generally involve chronic and subchronic rodent exposures with concomitant analyses of tumour induction (e.g., two-year rodent cancer bioassay), in addition to various non-cancer endpoints, the most sensitive of which is used for regulatory decision-making (Meek et al., 1994). These approaches form the foundation of the chemical regulatory system and have been invaluable for HHRA. However, some of these assays, such as those based on chronic animal exposures at the maximum tolerated dose, are time and resource intensive, thus limiting broad application (Suter et al., 2004).

1E). These preliminary data confirmed that the scFv was a reliable binder of the NPMc+ mutant and therefore we evaluated the possibility to express it as selleck screening library an intrabody in HeLa cell cytoplasm. HeLa cells were transiently co-transfected with NPMc+ and a scFv-GFP fusion. The frequency of cells co-expressing both constructs was always low (about 5%) but the homogeneous accumulation of green fluorescent (scFv-fusion) protein seems to indicate that the anti-NPMc+ antibody did not aggregate and that it mainly co-localized with its antigen in the cytoplasm (Fig. 2A–C). Similar results were obtained by infecting leukemic cells with retroviral and lentiviral vectors expressing the scFv

(data not shown). The immunoprecipitation results (Fig. 2D) confirmed that, upon transient co-expression, the scFv-Flag construct was functionally folded and effectively interacted with its antigen in the intracellular milieu, although at a low stoichiometic 3 MA ratio. Summarizing, the scFv specific for the C-terminus of the mutated NPMc+ could be expressed in the cytoplasm of mammalian cells as a functional intrabody. Consequently, we prepared a reagent composed by the fusion of the recombinant antibody together with

a NLS to evaluate the possibility to bind the cytoplasmic NPMc+ and relocate it into the nucleus. The scFv-NLS construct effectively accumulated into the nucleus (Fig. 3A) and co-accumulated with NPMc+ in the same compartment when the protein nuclear export was inhibited by treating the cells with leptomycin B, a CRM1-dependent nuclear export inhibitor (Fig. 3D). In the absence of leptomycin B treatment, the scFv failed to relocate the cytoplasmic mutant NPMc+ (Fig. 3B) and we observed rather the opposite, namely the antigen sequestered the antibody in the cytoplasm (Fig. 3C). The fusion of four NLS to the scFv did not modify the equilibrium (data not shown). Confocal microscopy imaging showed that NPMc+-GFP (Fig. 3E) accumulated very rapidly in the nuclei of leptomycin B-treated cells even in the absence of scFv-NLS

(Fig. 3F). The leptomycin B-dependent nuclear accumulation of NPMc+ and NPM1 in the nucleus was equally effective after 1 h (Fig. 3G and H) although the NPM1 protein accumulation was faster (data Baricitinib not shown). The relatively rapid accumulation of NPMc+ in the nucleus and the rare availability of co-transfected cells impaired to demonstrate a statistically significant contribution of scFv-NLS to the protein nuclear uptake (data not shown). Sub-cellular localization of proteins shuttling between nucleus and cytoplasm is the consequence of the dynamic equilibrium determined by the relative strength of the two opposite fluxes. In the case of NPM1, both NLS and NES putative motifs are embedded into the wild type sequence, as expected for a protein physiologically shuttling between nucleus and cytoplasm.

However, the current, preferred Canary Island model, considers a single, continuous, water table that domes steeply inland, to high elevation, over low permeability volcanic cores (Cabrera and Custodio, BLZ945 2004 and Custodio, 2007). The Canary Island model has also been proposed for similar ocean island volcanoes, including Pico Island in the Azores (Cruz and Silva, 2001) and Reunion Island (Join et al., 2005). However, the hydrology of volcanic arc islands is comparatively poorly studied. Robins

et al. (1990) identified three island hydrology types in the Lesser Antilles Island Arc, related to the abundance of rainfall and age of deposits. Type 1, based on Grenada and St Vincent, resembles the Canary Island model; a shallow water table doming steeply inland to elevations above 250 m, over a low permeability volcanic core, selleck screening library with springs at all elevations. Type 2 more closely resembles the Hawaiian model, but with the notable absence of impounding dykes. Type 2 is based on the islands of Saint Kitts and Nevis where the younger (Pleistocene) volcanic deposits support perched aquifers of limited capacity and ephemeral streams. Type 3 describes older, Eocene volcanic islands, such as the British Virgin Islands, with exposed low permeability cores and very limited exploitable groundwater potential in low lying alluvial deposits. Here we review the existing understanding of essential components

of Montserrat’s hydrological system. This review, which combines published literature and previously unpublished historical data, is supplemented by new observations, data collection and analysis. We provide new insights into hydrological inputs, measurements of aquifer Parvulin permeability, and geological and hydrological field observations from Montserrat. By combining these new observations and fresh analysis of existing data with our existing

understanding of some of the components of the hydrological system, we can begin to develop a conceptual model for the hydrology of Montserrat. The aim is to improve out fundamental understanding of the hydrology of Montserrat. This will inform and stimulate further investigation into hydrology of volcanic arc islands; in particular, exploration of the coupled hydrological, geomechanical and geophysical feedbacks associated with volcanic and tectonic activity, and assessment of the response of island groundwater resources to a changing climate. Montserrat is located at the northern end of the Lesser Antilles volcanic arc in the eastern Caribbean (Fig. 1). The island is made up almost exclusively of volcanic rocks erupted from four volcanic centres in three regions. North to south, these are: Silver Hills (SH; 2600–1200 ka), Centre Hills (CH; 950–550 ka) and the Soufrière Hills Volcano (SHV) – South Soufrière Hills (SSH) complex (174 ka to present) (Harford et al., 2002).

, 2012). In this context, this study, to the best of our knowledge, was the first to show that tDCS can reverse the effects of maladaptive plasticity as expressed by behavioral changes and measured by TNFα levels. On the other hand, one limitation of the study was the lack of difference between one of the analysis for von Frey test – S vs. SN – probably because of less sensitivity of this measurement as compared to hot plate test and also because of differences what these measurements index such as hot plate related to hyperalgesia and von Frey related to allodynia. In summary, we showed that

tDCS was able to reverse completely the detrimental effects of chronic stress find protocol on the pain system, as expressed by hyperalgesia and allodynia, and that this effect continued for 24 h. Serum levels of corticosterone and interleukin-1β were not changed by tDCS sessions or chronic restraint stress, but hippocampal TNFα levels decreased. Given that, in this study, animals were exposed to the same level of stress under the same

see more conditions, our findings support further exploration of tDCS as a therapeutic tool early in the exposure to stressful situations that may lead to chronic pain, such as post-traumatic stress disorder, and demonstrate one possible pathway of anodal tDCS treatment. Future studies should also consider assessing other outcomes of stress response, including other behavioral outcomes, as well as measurement of other biochemical variables, such as PCPA (inhibitor of serotonin synthesis), AMPT (inhibitor of tyrosine hydroxylase) and naloxone, to provide a better understanding of the effects of chronic restraint stress on mood and anxiety and further elucidate and

optimize this intervention into a potential clinical tool for stress-related conditions. Sixty-day-old male Wistar rats weighing 180–230 g were used. Experimentally naive animals were housed in groups of five in 49×34×16 cm polypropylene home cages. All animals were kept on a standard 12-hour light/dark cycle (lights Niclosamide on at 07:00 a.m. and lights off at 07:00 p.m.) in a temperature-controlled environment (22±2 °C). Animals had access to water and chow ad libitum. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No. 100.381) and performed in accordance with the Guide for the Care and Use of Laboratory Animals 8th edition (2011). Animal handling and all experiments were performed in accordance with International Guidelines for Animal Welfare and Measures were taken to minimize animal pain and discomfort. The experiment used the minimum number of animals required to produce reliable scientific data. To control the possible effect of outliers, we excluded rats which did not present any response on behavioral testing. All the experimenters were blinded to condition (active or sham tDCS) during post-treatment behavioral testing.

Distinguishing these infants may allow targeted interventions early in life to optimize adult health. In this study, we examined PHLDA2 expression in placentas of 102 infants born to mothers participating in the Southampton Women’s Survey for whom there is detailed information about fetal growth and placental weight at term [25]. In addition to measurements of fetal growth velocity, we correlated

placental expression of PHLDA2 with the infant’s anthropometry, bone mass PARP inhibitor and body composition at birth (measured by dual-energy X-ray absorptiometry (DXA)) and, where data were available, bone mass and body composition in early childhood. We found no significant relationship between PHLDA2 expression and birth weight in this cohort, but there were relationships between higher placental PHLDA2 expression and lower femur growth rate between 19 and 34 weeks of gestation and lower bone mineral content at 4 years. Details of the Southampton Women’s Survey (SWS) have been published previously [25]. In a group of pregnancies the placenta was collected within 30 min of delivery. The weight of the placenta Selleckchem PD-L1 inhibitor was measured after removing any obvious blood clots, cutting the umbilical cord

flush with its insertion into the placenta, trimming away surrounding membranes and removing the amnion from the basal plate. To ensure that samples collected were representative of the placenta as a whole, 5 villous tissue samples were selected using a stratified random sampling method and stored at − 80 °C. For this study, we selected 102 placentas (from 300 collected in total) based on availability of neonatal DXA data. In 58 pregnancies, measures of fetal size and growth velocity were available from ultrasound scans performed by a research sonographer at 19 and 34 weeks gestation. Using

a high resolution ultrasound Orotidine 5′-phosphate decarboxylase system (Kretz Voluson 730), head circumference (HC) was obtained using an ellipse superimposed on a static scan image of the horizontal plane at the level of the thalamus and the cavum septi pellucidi [26]. Abdominal circumference (AC) was also similarly measured using a transverse section of the fetal abdomen at the level of the fetal stomach and where a short section of umbilical vein can be identified. Femur length (FL) was measured in longitudinal section by placing the linear calipers at the ends of the diaphysis, with the femur horizontally positioned in the scan plane [26]. Three measurements were made of each parameter and the mean used in the statistical analysis [27]. Precision of the measurements was assessed by replicate examinations in 50 pregnancies at both 19 and 34 weeks. The coefficient of variation for triplicate linear measurements was 0.6% at 19 weeks and 0.4% at 34 weeks [27]. For elliptical measurements the values were 4.4% at 19 and 3.2% at 34 weeks.

In five studies the control group received no intervention, whereas in six studies the control group was given education, and in one study therapeutic ultrasound ( Deyle 2000). In five of the twelve studies both weight bearing and non-weight bearing strength exercise programs were chosen, while five studies only used nonweight bearing and two only weight bearing strength exercises. See Table 3 for a Selleckchem AZD6244 description of the main aspects of the studies. Outcome measures: Most studies used the WOMAC to analyse the effects on pain and function. Effect sizes

could not be calculated for four studies, because standard deviations were missing ( Ettinger et al 1997, Maurer et al 1999), total WOMAC scores selleck compound (instead of the pain and function subscale scores) were presented ( Deyle et al 2000), or the results pertained to a mixed group of patients suffering from either hip or knee osteoarthritis ( van Baar et al 1998). In the review by Fransen and McConnell (2008), the effect sizes for these four studies were calculated with the help of externally provided data. We used these effect sizes on the assumption that these data had been correctly calculated. We could not retrieve and analyse separate results for patients with knee and hip osteoarthritis from one study ( Hughes et al 2006). Generally, effects for knee and hip osteoarthritis

have been found to be the same ( Jansen et al 2010, van Baar et al 1998), so we used the results for the total group, assuming comparable effect sizes. Finally, for the study by Fransen and colleagues (2001), we assumed that the change between baseline and Week 8 was the same for the two intervention groups. The 16-week results could not be used, since these include control participants that were randomised to the two intervention groups after Week 8. Pain: Figure 2 presents the results for pain. The effect size on pain was 0.38 (95% CI 0.23 to 0.54) for strength training, 0.34 (95% CI 0.19 to 0.49) for exercise therapy,

and 0.69 (95% CI 0.42 to 0.96) for exercise therapy plus manual mobilisation. On the meta-regression, Thiamet G only the difference between exercise therapy and exercise therapy with additional manual mobilisation was significant (p = 0.03), although the difference between strength training and exercise therapy with additional manual mobilisation was close to being significant (p = 0.06). Physical function: The effect size on physical function was 0.41 (95% CI 0.17 to 0.66) for strength training, 0.25 (95% CI 0.03 to 0.48) for exercise and 0.43 (95% CI 0.05 to 0.81) for exercise therapy with additional manual mobilisations (see Figure 3). With meta-regression, no significant differences were found between the effect sizes of the different interventions with respect to physical functioning. Generally, the effect sizes for function tended to be smaller than those for pain (see Figure 4).