Immunogenicity of pneumococcal conjugate vaccine formulations containing pneumococcal proteins, and immunogenicity and reactogenicity of co-administered routine vaccines - A phase II, randomised, observer-blind study in Gambian infants.

BACKGROUND: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. METHODS: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. RESULTS: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. CONCLUSION: Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872

Immunocytochemical localization of human growth hormone-like and prolactin-like antigenic determinants in the insects, Locusta migratoria and Sarcophaga bullata

1. By use of the peroxidase-antiperoxidase immunocytochemical method, substances immunoreactive to antisera directed against human growth hormone (hGH) and prolactin (hPrl) were localized in the nervous system of larval and adult Locusta migratoria and of adult Sarcophaga bullata belonging to different age groups. 2. No major differences in the distribution of cerebral immunoreactive materials were observed between males and females or between juvenile and adult insects. 3. Differential immuno-labeling of alternating tissue sections demonstrated that materials resembling hGH or hPrl are present in distinct neurons in the locust, whereas neurons immunoreactive to both antisera were detected in the fleshfly (Sarcophaga).status: publishe

Joint surface lesions in the knee treated with an acellular aragonite-based scaffold : a 3-year follow-up case series

OBJECTIVE: The study aimed to evaluate the clinical outcome and repair capacity of a cell-free aragonite-based scaffold in patients with an isolated symptomatic joint surface lesion (JSL) of the knee. DESIGN: Thirteen patients (age 33.5 ± 8.9; female 23%; body mass index 25.3 ± 3.4, K/L [Kellgren-Lawrence] 1.8) with a JSL (2.6 ± 1.7 cm(2) [1.0-7.5 cm(2)]) of the distal femur were enrolled in a single-center prospective case series. Safety and clinical outcome was assessed by the KOOS (Knee Injury and Osteoarthritis Outcome Score), IKDC (International Knee Documentation Committee), Lysholm, and Tegner activity scale at baseline and 6, 12, 18, 24, and 36 months follow-up. The MOCART 2.0 and scaffold integration were evaluated on magnetic resonance imaging at 12, 24, and 36 months postoperatively. RESULTS: Primary outcome (KOOS pain) improved with 36.5 ± 14.7 points at 12 months (P = 0.002) and 41.2 ± 14.7 points at 36 months (P = 0.002) follow-up. Similar increasing trends were observed for the other KOOS subscales, IKDC, and Lysholm score, which were significantly better at each follow-up time point relative to baseline (P < 0.05). Activity level increased from 2.75 ± 1.6 to 4.6 ± 2.2 points at final follow-up (P = 0.07). The MOCART was 61.7 ± 12.6 at 12 months and 72.9 ± 13.0 at 36 months postoperatively. Sixty-six to 100% implant integration and remodeling was observed in 73.3% cases at 36 months. No serious adverse events were reported. CONCLUSION: The study demonstrated that the biphasic aragonite-based scaffold is a safe and clinically effective implant for treating small-medium sized JSLs of the distal femur in a young and active patient cohort. The implant showed satisfying osteointegration and restoration of the osteochondral unit up to 3 years postimplantation

Detection of substances recognized by antisera directed against vertebrate somatotropin, prolactin and placental lactogen, within the brain of the insect Locusta migratoria - a comparison of immunocytochemical localization patterns

1. 1. Substances immunoreactive to antibodies directed against human prolactin (hPrl), human somatotropin (hGH), human chorionic somatomammotropin (hCS), bovine growth hormone (bGH, three antisera) and chicken growth hormone (chGH) were localized in the brain of Locusta migratoria by means of the peroxidase-antiperoxidase method. 2. 2. The malpighian tubule epitheliar cells were found to be 'chGH'-immunopositive. 3. 3. The immunoreactivity distributions obtained by these antisera were almost entirely different. © 1990.status: publishe

Autologous Micro-Fragmented Adipose Tissue (MFAT) to treat symptomatic knee osteoarthritis : early outcomes of a consecutive case series

The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects with symptomatic mild–severe knee OA were enrolled in a single-center trial and received a unilateral (n = 37) or bilateral (n = 27) MFAT injection. After liposuction, the adipose tissue was mechanically processed with the Lipogem(®) device, which eventually produced 8–10 cc of MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA, and EQ-5D at baseline and 1, 3, 6, and 12 months after injection. Adverse events were recorded at each follow-up timepoint. The TRR was defined according to the OMERACT-OARSI criteria and baseline MRI was scored following the MOAKS classification. The TRR of the index knee was 64% at 3 months and 45% at 12 months after injection. Therapy responders at 12 months improved with 28.3 ± 11.4 on KOOS pain, while non-responders lost −2.1 ± 11.2 points. All clinical scores, except the UCLA, improved significantly at follow-up compared to baseline (p < 0.05). In the bilateral cohort, no difference in baseline scores or TRR was found between the index knee and contralateral knee (n.s.). An inflammatory reaction was reported in 79% of knees and resolved spontaneously within 16.6 ± 13.5 days after MFAT administration. Numerous bone marrow lesions (BML) were negatively correlated with the TRR at 12 months (p = 0.003). The study demonstrated an early clinical improvement but a mediocre response rate of 45% at 12 months after a single intra-articular injection with autologous MFAT. Assessment of bone marrow lesions on MRI can be helpful to increase the therapeutic responsiveness of MFAT up to 70% at 12 months. In comparison to repetitive injection therapies such as cortisone, hyaluronic acid, and PRP, administration of MFAT might become a relevant alternative in well-selected patients with symptomatic knee OA

Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. Methods: We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Results: Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Conclusions: Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated

Does a cycling program combined with education and followed by coaching promote physical activity in subacute stroke patients? A randomized controlled trial

<p><b>Background:</b> To investigate the effects of a three month active cycling program followed by coaching on physical activity in subacute stroke patients.</p> <p><b>Methods:</b> Patients (<i>n</i> = 59; mean age =65.4 ± 10.3) aged ≤80 years with first stroke and able to cycle at 50 revolutions/minute enrolled 3–10 weeks post stroke. Patients were randomly allocated to three month active cycling group (<i>n</i> = 33) or to a control group (<i>n</i> = 26), 3 x 30 minutes training/week. Afterwards, the active cycling group was randomized into a coaching (<i>n</i> = 15) versus non-coaching group (<i>n</i> = 16) for nine months. Physical activity was measured by objective and self-reported measures, which were taken before/after the active cycling program and during six and 12 months, except the Baecke-questionnaire, which was used at baseline and 12 months.</p> <p><b>Results:</b> A significant difference was found in Baecke/sport (95% confidence interval: 0.06, 2.24; <i>p</i> = 0.039) between the active cycling group and the control group, in patients with severe motor function deficits at baseline. Patients in the control group performed significant less sports at 12 months (mean Baecke/sport_baseline =3.07 ± 1.21, mean Baecke/sport_12months = 1.43 ± 0.98; <i>p</i> = 0.01). Furthermore, all groups showed significant changes over time in all measures at three months (except: Physical Activity Scale for Individuals with Physical Disabilities, diary/Mets*minutes-moderate) and 12 month and additionally in a subgroup with severe motor function deficits (except diary Mets*minutes-sedentary).</p> <p><b>Conclusion:</b> When active cycling combined with education is used in subacute patients with severe motor function deficits, more sport participation might be observed after one year. No other significant group differences were found over time. In all groups, however, patients showed significant improvement over time in physical activity measures. Future work is needed to explore the most effective coaching approach after an aerobic training program.Implications for Rehabilitation</p><p>The active cycling program combined with education is applicable in subacute stroke patients as it required little stand-by assistance due to chip cards, the intensity was gradually built and the involvement of caregivers in the educational sessions. This training approach also revealed applicable in severely impaired stroke patients and might facilitate sport participation on the long-term.</p><p>This randomized controlled study aims to quantify physical activity after stroke by using a combination of objective and self-report measures, which revealed detailed information about different aspects of physical activity levels.</p><p>There is a need for coaching approaches that facilitate aerobic exercise after ending a supervised program. A coaching approach needs to guide patients in adopting aerobic exercise as a part of a lifestyle change and needs to be less time consuming.</p><p></p> <p>The active cycling program combined with education is applicable in subacute stroke patients as it required little stand-by assistance due to chip cards, the intensity was gradually built and the involvement of caregivers in the educational sessions. This training approach also revealed applicable in severely impaired stroke patients and might facilitate sport participation on the long-term.</p> <p>This randomized controlled study aims to quantify physical activity after stroke by using a combination of objective and self-report measures, which revealed detailed information about different aspects of physical activity levels.</p> <p>There is a need for coaching approaches that facilitate aerobic exercise after ending a supervised program. A coaching approach needs to guide patients in adopting aerobic exercise as a part of a lifestyle change and needs to be less time consuming.</p