Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats ...(Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.
In this study, an IgG-degrading enzyme derived from
Streptococcus pyogenes
(IdeS) that cleaves human IgG into F(ab′)
2
and Fc fragments reduced or eliminated donor-specific antibodies and permitted ...HLA-incompatible renal transplantation.
Low survey response rates in general practice are common and lead to loss of power, selection bias, unexpected budgetary constraints and time delays in research projects.
To assess the effectiveness ...of recruitment strategies aimed at increasing survey response rates among GPs.
Systematic review.
MEDLINE (OVIDSP, 1948-2012), EMBASE (OVIDSP, 1980-2012), Evidence Based Medicine Reviews (OVIDSP, 2012) and references of included papers were searched. Major search terms included GPs, recruitment strategies, response rates, and randomised controlled trials (RCT).
Cluster RCTs, RCTs and factorial trial designs that evaluate recruitment strategies aimed at increasing GP survey response rates.
Abstracts identified by the search strategy were reviewed and relevant articles were retrieved. Each full-text publication was examined to determine whether it met the predetermined inclusion criteria. Data extraction and study quality was assessed by using predetermined checklists.
Monetary and nonmonetary incentives were more effective than no incentive with monetary incentives having a slightly bigger effect than nonmonetary incentives. Large incentives were more effective than small incentives, as were upfront monetary incentives compared to promised monetary incentives. Postal surveys were more effective than telephone or email surveys. One study demonstrated that sequentially mixed mode (online survey followed by a paper survey with a reminder) was more effective than an online survey or the combination of an online and paper survey sent similtaneously in the first mail out. Pre-contact with a phonecall from a peer, personalised packages, sending mail on Friday, and using registered mail also increased response rates in single studies. Pre-contact by letter or postcard almost reached statistical signficance.
GP survey response rates may improve by using the following strategies: monetary and nonmonetary incentives, larger incentives, upfront monetary incentives, postal surveys, pre-contact with a phonecall from a peer, personalised packages, sending mail on Friday, and using registered mail. Mail pre-contact may also improve response rates and have low costs. Improved reporting and further trials, including sequential mixed mode trials and social media, are required to determine the effectiveness of recruitment strategies on GPs' response rates to surveys.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of ...evaluation and treatment in patients from the REAL-B consortium.
This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses.
We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio aOR 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001).
Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.
Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.
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•Among 12,566 patients with chronic HBV infection, about one-quarter were not adequately evaluated.•Among adequately evaluated patients, about one-third were treatment eligible by international guidelines.•Among those who were treatment eligible, about 80-85% were treated.•Treatment rates were lower in females and Asian Americans (vs. Asians from the East or non-Asians).
Delayed graft function (DGF) is defined as need for dialysis early posttransplant. DGF is related to ischemia–reperfusion injury (IRI) that diminishes allograft function and may be complement ...dependent. Here, we investigate the ability of C1 esterase inhibitor (C1INH) to prevent IRI/DGF in kidney transplant recipients. Seventy patients receiving deceased donor kidney transplants at risk for DGF were randomized to receive C1INH 50 U/kg (#35) or placebo (#35) intraoperatively and at 24 hours. The primary end point was need for hemodialysis during the first week posttransplant. Assessments of glomerular filtration rate and dialysis dependence were accomplished. Complications and safety of therapy were recorded. Similar characteristics with no significant differences in cold‐ischemia time or risk factors for DGF were seen. C1INH did not result in reduction of dialysis sessions at 1 week posttransplant, but significantly fewer dialysis sessions (P = .0232) were required 2 to 4 weeks posttransplant. Patients at highest risk for DGF (Kidney Donor Profile Index ≥85) benefited most from C1INH therapy. Significantly better renal function was seen at 1 year in C1INH patients (P = .006). No significant adverse events were noted with C1INH. Although the primary end point was not met, significant reductions in need for dialysis and improvements in long‐term allograft function were seen with C1INH treatment.
In a placebo‐controlled study for prevention of delayed graft function in kidney allografts, C1 esterase inhibitor demonstrates a significant benefit in improving renal function compared to placebo.
Foot-and-mouth disease is a highly contagious disease that affects cloven-hoofed animals. It has an important socio-economic impact on the livestock industry because it produces a drastic decrease of ...productivity. The disease has been successfully eradicated from some regions, including North America and Western Europe, but it is still endemic in developing countries. Agriculture plays an important role in the national economy of Vietnam, to which animal production contributes a great proportion. The concurrent circulation of foot-and-mouth disease virus (FMDV) serotypes O, A, and Asia 1 has been detected in recent years, but serotype O remains the most prevalent and is responsible for the highest numbers of outbreaks. Appropriate vaccine strain selection is an important element in the control of FMD and is necessary for the application of vaccination programs in FMD-affected regions. Here, we present updated information about the genetic and antigenic characteristics of circulating strains, collected from endemic outbreaks involving types O and A, between 2010 and 2019. Neutralizing assays showed a good
in vitro
match between type O strains and the monovalent O1 Campos vaccine strain. High r1 values were obtained (above 0.7) when testing a swine serum pool collected 21 days after vaccination, but the O/VTN/2/2019 strain was an exception. An EPP estimation resulted in a median neutralizing titre of about 1.65 log10, indicating that good protection could be achieved. For type A Asia SEA 97 lineage strains, acceptable individual neutralizing titres were obtained with estimated EPP values over 80% for different combinations of vaccine strains. Taking into account that the r1 value is one tool of a battery of tests that should be considered for estimating the cross-protection of a field strain against a vaccine strain, an
in vivo
challenge experiment was also performed, yielding a PD
50
value of 8.0. The results indicate that South American strains could be potentially used for controlling outbreaks involving these lineages. This study demonstrates the importance of considering strain characteristics when choosing vaccine strains and controls.
BACKGROUND.Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important pathway responsible for antibody-mediated rejection (AMR). Imlifidase (IdeS) cleaves human IgG into F(ab’)2 and Fc ...fragments, potentially inhibiting ADCC. Here we examined the effect of IdeS on allo-antibody-mediated NK cell activation (Allo-CFC) and ADCC in vitro.
METHODS.For Allo-CFC, normal whole blood was incubated with third-party peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody positive (HS) or negative (NC) sera to measure IFNγ+ NK cell%. For ADCC, normal PBMCs were incubated with Farage B (FB) cells with HS or NC sera to measure 7-AAD+ lysed FB cell%. To assess the effect of IdeS on these assays, serum-treated PBMCs (Allo-CFC-1) and serum used for PBMC pretreatment (Allo-CFC-2) in Allo-CFC, and serum used for ADCC were preincubated with IdeS. Sera from IdeS-treated patients were also tested for Allo-CFC (Allo-CFC-3).
RESULTS.IFNγ+ NK cell% were significantly elevated in HS versus NC sera in Allo-CFC-1 (10 ± 3% versus 2 ± 1%, P = 0.001), Allo-CFC-2 (20 ± 10% versus 4 ± 2%, P = 0.01) and 7AAD+ FB cell% (11 ± 3% versus 4 ± 2%, P = 0.02) in ADCC. These were significantly reduced by IdeS treatment. Patient sera with significantly reduced anti-HLA antibody levels at 1 day postimlifidase lost the capacity to activate NK cells in Allo-CFC-3, but those at 1–3 months postimlifidase regained the capacity.
CONCLUSIONS.IdeS inhibited NK cell activation and ADCC in vitro and in treated patients. These results and reported inhibition of complement activating anti-HLA antibodies by IdeS suggest its possible role in treatment of AMR.
•The challenge on automatic tool annotation for cataract surgery is presented.•Tool usage was manually annotated for 21 tools in 50 cataract surgery videos.•Various deep learning solutions were ...proposed by 14 teams.•Lessons learnt from the differential analysis of these solutions are presented.•Automatic annotations are almost as accurate as manual annotations.
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Surgical tool detection is attracting increasing attention from the medical image analysis community. The goal generally is not to precisely locate tools in images, but rather to indicate which tools are being used by the surgeon at each instant. The main motivation for annotating tool usage is to design efficient solutions for surgical workflow analysis, with potential applications in report generation, surgical training and even real-time decision support. Most existing tool annotation algorithms focus on laparoscopic surgeries. However, with 19 million interventions per year, the most common surgical procedure in the world is cataract surgery. The CATARACTS challenge was organized in 2017 to evaluate tool annotation algorithms in the specific context of cataract surgery. It relies on more than nine hours of videos, from 50 cataract surgeries, in which the presence of 21 surgical tools was manually annotated by two experts. With 14 participating teams, this challenge can be considered a success. As might be expected, the submitted solutions are based on deep learning. This paper thoroughly evaluates these solutions: in particular, the quality of their annotations are compared to that of human interpretations. Next, lessons learnt from the differential analysis of these solutions are discussed. We expect that they will guide the design of efficient surgery monitoring tools in the near future.
The TIS11/tristetraprolin (TTP) CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3′ untranslated regions. In this report, ...we demonstrate that the
Drosophila melanogaster
dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated with the intrinsically unstructured, disordered N- and C-terminal domains of the protein. Furthermore, we show that TTP, the mammalian TIS11/TTP protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism has been conserved across evolution. Finally, we observed a phosphorylation-dependent inhibition of dTIS11 and TTP degradation by the proteasome in vitro, raising the possibility that such modifications directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BPs) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism that we uncovered for TIS11/TTP turnover is widespread among other RNA-BPs.
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