economically impacts cattle production in tropical and subtropical countries. Application of acaricides constitutes the major control method; however, inadequate use has increased resistant tick ...populations, resulting in environmental and cattle product contamination. Anti-tick vaccines based on the Bm86 antigen are an environmentally friendly, safe, and economically sustainable alternative for controlling
infestations. Nevertheless, variable efficacy has been experienced against different geographic tick strains. Herein, we evaluated the efficacy of a conserved polypeptide Bm86 derived from a Mexican
strain previously characterized. Twelve cows were assigned to three experimental groups and immunized with three doses of the polypeptide Bm86 (pBm86), adjuvant/saline alone, and Bm86 antigen (control +), respectively. Specific IgG antibody levels were measured by ELISA and confirmed by Western blot. In addition, the reproductive performance of naturally infested
was also determined. The more affected parameter was the adult female tick number, with a reduction of 44% by the pBm86 compared to the controls (
< 0.05), showing a vaccine efficacy of 58%. Anti-pBm86 IgG antibodies were immunogenic and capable of recognizing the native Bm86 protein in the eggs, larvae, and guts of
. The negative correlation between antibody levels and the reduction of naturally tick-infested cattle suggested that the effect of the polypeptide Bm86 was attributed to the antibody response in immunized cattle. In conclusion, the polypeptide Bm86 showed a specific immune response in cattle and conferred protection against
in a Mexican tropical region. These findings support further experiments with this antigen to demonstrate its effectiveness as a regional vaccine.
Background and study aims:
Overall, 5 % to 15 % of patients undergoing cholecystectomy for cholelithiasis have concomitant bile duct stones, and the incidence of choledocholithiasis increases with ...age. There is no clear consensus on the best therapeutic approach (endoscopic versus surgical).
Patients and methods:
A prospective randomized controlled clinical trial was performed to compare three treatment options for patients with choledocholithiasis at the National Center for Minimally Invasive Surgery in Havana, Cuba from November 2007 to November 2011. The patients were randomized in three groups. Group I: patients who underwent intraoperative cholangiography (IOC) to confirm the choledocholithiasis followed by laparoscopic cholecystectomy (LC) associated with intraoperative endoscopic retrograde cholangiopancreatography (ERCP), group II: patients who underwent preoperative ERCP followed by LC during the same hospital admission and group III: patients who underwent IOC to confirm the choledocholithiasis followed by LC associated with laparoscopic common bile duct exploration (LCBDE).
Results:
A total of 300 patients with suspected choledocholithiasis were included in the trial and were randomized. As a result, a total of 134 patients were diagnosed with the presence of choledocholithiasis and treated during the study period. There were no significant differences in success rates of ductal stone clearance, but retained stone, postoperative complications and length of hospital stay were better in group I.
Conclusions:
Intraoperative ERCP/ES shows a higher rate of common bile duct stones clearance, a shorter hospital stay, and lower morbidity, but further research with a larger study population is necessary to determine the additional benefits of this procedure. The results to date suggests that in appropriate patients, single-stage treatments are the best options.
Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia’s ...inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide LPS injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.
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•Gal3 acts as an endogenous TLR4 ligand with a Kd value around 1 μM•Gal3 can initiate a TLR4-dependent inflammatory response in microglia•Gal3 is required for complete activation of TLR4 upon LPS treatment•Gal3-TLR4 interaction is confirmed in vivo and in stroke patients
In this publication, Burguillos et al. demonstrate how galectin-3 (Gal3) released from reactive microglia cells can activate other surrounding immune cells in a paracrine manner by binding to and activating Toll-like receptor 4 (TLR4). This finding could explain the propagation of the inflammatory response once the initial stimulus is gone.
Objective
: To test the hypothesis that specific psychopathological non-cognitive symptoms are associated with incident mild cognitive impairment (MCI), while different symptoms are associated with ...incident dementia of Alzheimer’s type (DAT).
Methods
: A representative community sample of 4,803 individuals aged 55+ years was interviewed in a two-phase screening, in Wave I or ZARADEMP I. This is the baseline, cross-sectional study of the ZARADEMP Project, a longitudinal study to document incidence and risk factors of dementia. The main instrument for assessment of participants was the ZARADEMP Interview, which includes standardized Spanish versions of instruments such as the Mini-Mental Status Examination and the Geriatric Mental State GMS-AGECAT. Two years later, in Wave II or ZARADEMP II, the cognitively non-deteriorated elderly were reassessed in a similar, two-phase procedure. “Incident cases” of both dementia and DAT (DSM-IV-TR criteria), as well as MCI (operationally defined Petersen’s criteria) were diagnosed by a panel of psychiatrists. Statistical, logistic regression models, adjusted by age, sex and education were used to test the hypothesized association.
Results
: “Irritability”, “neurovegetative symptoms”, “sleep problems”, “concentration ifficulties”, “loneliness” and “subjective slowing” documented at baseline were associated with incident MCI (odds ratio, OR range 1.71-2.67). A different profile of non-cognitive symptoms was associated with incident DAT, specifically “tension” (OR= 2.45), “sleep problems” (OR= 2.81), and “observed slowing” (OR= 4.35). On the contrary, “subjective restriction of activities” seemed to be negatively associated with DAT (OR= 0.12).
Conclusions
: To our knowledge, this is the first report about some specific psychopathological, non-cognitive symptoms associated with incident MCI and/ or incident DAT, when controlling by each other. The psychopathological profile associated with MCI is different from the profile preceding DAT.
To test the hypothesis that clinically significant depression (particularly severe depression) increases the risk of Alzheimer's disease (AD).
A longitudinal, three-wave epidemiologic study was ...implemented in a sample of individuals aged 55 years and older (n = 4,803) followed up at 2.5 years and 4.5 years. This was a population-based cohort drawn from the Zaragoza Dementia and Depression (ZARADEMP) Project, in Zaragoza, Spain. Participants included individuals cognitively intact at baseline (n = 3,864). The main outcome measures were depression as assessed by using the diagnostic interview Geriatric Mental State- Automated Geriatric Examination for Computer Assisted Taxonomy package; and AD diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Fine and Gray multivariate regression model was used in the analysis, accounting for mortality.
At baseline, clinically significant depression was diagnosed in 452 participants (11.7%); of these, 16.4% had severe depression. Seventy incident cases of AD were found at follow-up. Compared with nondepressed individuals, the incidence rate of AD was significantly higher in the severely depressed subjects (incidence rate ratio: 3.59 95% confidence interval: 1.30-9.94). A consistent, significant association was observed between severe depression at baseline and incident AD in the multivariate model (hazard ratio: 4.30 95% CI: 1.39-13.33). Untreated depression was associated with incident AD in the unadjusted model; however, in the final model, this association was attenuated and nonsignificant.
Severe depression increases the risk of AD, even after controlling for the competing risk of death.
Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with ...acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke.
The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.
Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 95% CI 0·55–7·85; p=0·28), eight (44%) in the high-dose group (1·89 0·52–6·96; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 0·72–6·85; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.
Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.
Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.
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