77 research outputs found

    Effect of Preventive Chlamydia abortus Vaccination in Offspring Development in Sheep Challenged Experimentally

    Get PDF
    Ovine enzootic abortion, caused by Chlamydia abortus, leads to important economic losses worldwide. In addition to reproductive failures, infection may impact lamb growth during the first weeks after birth, yet this effect has not been well characterized. Vaccination can help to control the disease but variable efficacy values have been described, possibly related with factors associated with the host, the vaccine, the parameter used for efficacy determination and the challenge conditions. In this context, we evaluated the efficacy of an inactivated standard commercial vaccine and a 1/2 diluted dose in pregnant sheep challenged with C. abortus by examining multiple indicators ofvaccine effect (including incidence of reproductive failures, bacterial excretion, and evolution of weight gain of viable lambs during the first month of life). Three groups of ewes [control non-vaccinated, C (n = 18); vaccinated with standard dose, SV (n = 16) and vaccinated with 1/2 dose, DV (n = 17)], were challenged approximately 90 days post-mating and tested using direct PCR (tissue samples and vaginal swabs) and ELISA (serum) until 31 days post-reproductive outcome. There were not significant differences in the proportions of reproductive failures or bacterial shedding after birth/abortion regardless the vaccination protocol. However, a beneficial effect of vaccination on offspring growth was detected in both vaccinated groups compared with the controls, with a mean increase in weight measured at 30 days of life of 1.5 and 2.5 Kg (p = 0.056) and an increase in the geometric mean of the daily gain of 8.4 and 9.7% in lambs born from DV and SV ewes compared to controls, respectively. Our results demonstrate the effect of an inactivated vaccine in the development of the offspring of C. abortus-infected ewes at a standard and a diluted dose, an interesting finding given the difficulty in achieving sufficient antigen concentration in the production of EAE-commercial vaccines

    Psychological burden of hepatic encephalopathy on patients and caregivers

    Get PDF
    Objectives: Hepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers. Methods: Fifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology. Results: HE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients. Discussion: HE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated

    Further Characterization of the Electrogenicity and pH Sensitivity of the Human Organic Anion-Transporting Polypeptides OATP1B1 and OATP1B3

    Get PDF
    Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential (ΔΨ) was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability increased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differently the specific transport of taurocholic acid (TCA) and estradiol 17β-d-glucuronide (E217βG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin (K+-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin (protonophores), and amiloride (Na+/H+-inhibitor) and cation replacement in the medium were studied with fluorescent probes for measuring substrate uptake (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and ΔΨ [DilC1(5)]. The results suggest that activity of these three carriers is sodium/potassium-independent and affected differently by changes in pHo and ΔΨ: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude of ΔΨ. Moreover, electrophysiological measurements revealed the existence of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA, E217βG, and estrone-3-sulfate. Furthermore, a leakage of Na+ through OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic transporters whose activity may be strongly affected under circumstances of displacement of local pH

    Assessment of genetic diversity of zoonotic Brucella spp. recovered from livestock in Egypt using multiple locus VNTR analysis

    Get PDF
    Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat) from four governorates during a period of five years (2002-2007) was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing). Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n = 2) and B. suis biovar 1 (n = 2). MLVA-15 yielded a high discriminatory power (h = 0.801), indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region

    Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern

    Get PDF
    The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to Public Health, by Grants PI19CIII/00004 (José Alcamí and Francisco Díez‐Fuertes) and PI21CIII/00025 (Javier García‐Pérez and Mayte Pérez‐Olmeda), COVID‐19 Fund (Grants COV20/00679 (Javier García‐Pérez, Mayte Pérez‐Olmeda, José Alcamí, and Francisco Díez‐Fuertes) and COV20/00072 (Javier García‐Pérez, Mayte Pérez‐Olmeda, Almudena Ramírez‐García, María Castillo de la Osa, Rocio Layunta Acero, Laura Vicente‐Izquierdo, Cristina Avendaño‐Solá, and José Alcamí), and CIBERINFEC, co‐financed by the European Regional Development Fund (FEDER) “A way to make Europe.”S

    Measuring health-related quality of life in men with osteoporosis or osteoporotic fracture

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Osteoporosis is a serious health problem that worsens the quality of life and the survival rate of individuals with this disease on account the osteoporotic fractures. Studies have long focused on women, and its presence in men has been underestimated. While many studies conducted in different countries mainly assess health-related quality of life and identify fracture risks factors in women, few data are available on a Spanish male population.</p> <p>Methods/Design</p> <p>Observational study.</p> <p>Study population</p> <p>Men ≥ 40 years of age with/without diagnosed osteoporosis and with/without osteoporotic fracture included by their family doctor.</p> <p>Measurements</p> <p>The relationship between customary clinical risk factors for osteoporotic fracture and health-related quality of life in a Spanish male population. A telephone questionnaire on health-related quality of life is made.</p> <p>Statistical analysis</p> <p>The association between qualitative variables will be assessed by the Chi-square test. The distribution of quantitative variables by Student's t-test. If the conditions for using this test are not met, the non-parametric Mann-Whitney's U test will be used.</p> <p>The validation of the results obtained by the FRAX™ tool will be performed by way of the Hosmer-Lemeshow test and by calculating the area under the Receiver Operating Characteristic (ROC) curve (AUC). All tests will be performed with a confidence intervals set at 95%.</p> <p>Discussion</p> <p>The applicability and usefulness of Health-related quality of life (HRQOL) studies are well documented in many countries. These studies allow implementing cost-effective measures in cases of a given disease and reducing the costly consequences derived therefrom. This study attempts to provide objective data on how quality of life is affected by the clinical aspects involved in osteoporosis in a Spanish male population and can be useful as well in cost utility analyses conducted by health authorities.</p> <p>The sample selected is not based on a high fracture risk group. Rather, it is composed of men in the general population, and accordingly comparisons should not lead to erroneous interpretations.</p> <p>A possible bias correction will be ensured by checking reported fractures against healthcare reports and X-rays, or by consulting health care centers as applicable.</p

    Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Age-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.</p> <p>Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.</p> <p>Methods/Design</p> <p>To assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. Study population: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. Measurements: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.</p> <p>Discussion</p> <p>Since more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.</p

    Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in a Population at High Risk of Mpox: A Spanish Cohort Study

    Get PDF
    Background: With over 7,500 cases notified since April 2022, Spain has experienced the highest incidence of mpox in Europe. From July 12th onwards, the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for individuals at high-risk of mpox, including those receiving pre-exposure prophylaxis for HIV (HIV-PrEP). Our aim was to assess the effectiveness of one dose of MVA-BN vaccine as pre-exposure against mpox virus (MPXV) infection in persons on HIV-PrEP. Methods: We conducted a national retrospective cohort study between July 12 and December 12, 2022. Individuals ≥18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of MVA-BN vaccine and unvaccinated controls of the same age group and region. We used a Kaplan-Meier estimator and calculate risk ratios (RR) and vaccine effectiveness (VE = 1-RR). Results: We included 5,660 matched pairs, with a median follow-up of 62 days (interquartile range 24-97). Mpox cumulative incidence was 5.6 per 1,000 (25 cases) in unvaccinated and 3.5 per 1,000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE -38.3; 95% confidence interval (95%CI): -332.7; 46.4), but VE was 65% in ≥7 days (95%CI 22.9; 88.0) and 79% in ≥14 days (95%CI 33.3; 100.0) post-vaccination. Conclusions: One dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.S

    Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

    Full text link
    We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2
    corecore