Estimating the protection afforded by foot-and-mouth disease vaccines in the laboratory

Foot-and-mouth disease (FMD) vaccines must be carefully selected and their application closely monitored to optimise their effectiveness. This review covers serological techniques for FMD vaccine quality control, including potency testing, vaccine matching and post-vaccination monitoring. It also discusses alternative laboratory procedures, such as antigen quantification and nucleotide sequencing, and briefly compares the approaches for FMD with those for measuring protection against influenza virus, where humoral immunity is also important. Serology is widely used to predict the protection afforded by vaccines and has great practical utility but also limitations. Animals differ in their responses to vaccines and in the protective mechanisms that they develop. Antibodies have a variety of properties and tests differ in what they measure. Antibody-virus interactions may vary between virus serotypes and strains and protection may be affected by the vaccination regime and the nature and timing of field virus challenge. Finally, tests employing biological reagents are difficult to standardise, whilst cross-protection data needed for test calibration and validation are scarce. All of this is difficult to reconcile with the desire for simple and universal criteria and thresholds for evaluating vaccines and vaccination responses and means that oversimplification of test procedures and their interpretation can lead to poor predictions. A holistic approach is therefore recommended, considering multiple sources of field, experimental and laboratory data. New antibody avidity and isotype tests seem promising alternatives to evaluate cross-protective, post-vaccination serological responses, taking account of vaccine potency as well as match. After choosing appropriate serological tests or test combinations and cut-offs, results should be interpreted cautiously and in context. Since opportunities for experimental challenge studies of cross-protection are limited and the approaches incompletely reflect real life, more field studies are needed to quantify cross-protection and its correlation to in vitro measurements

Early pathological gambling in co-occurrence with semantic variant primary progressive aphasia: A case report

We have comprehensively documented a case of semantic variant of primary progressive aphasia (sv-PPA) presenting with early-onset pathological gambling (PG). While a growing number of studies have shown the presence of behavioral alterations in patients with sv-PPA, PG has been observed only in the behavioral variant of frontotemporal dementia (bv-FTD). To date, no case of PG with the co-occurrence of prominent semantic deficits at the onset of the disease has been reported in the literature. Impulse disorders at onset may wrongly lead to a misdiagnosis (ie, psychiatric disorders). Therefore, a wider characterization of cognitive/aphasia symptoms in patients presenting impulse disorders and predominant language dysfunctions is recommended

Age-related hearingimpairment and frailty in Alzheimer’s disease: interconnected associations and mechanisms

Among potentially modifiable age-related conditions linked to dementia, Alzheimer’s disease (AD),and late-life cognitive disorders, age-related hearing impairment (ARHI) or resbycusis is themost widely diffused sensory disorder and one of the principal causes of chronic disability inolder adults (Gates and Mills, 2005). The impairments of peripheral (sensory or strial) and central(predominantly neural) auditory pathways, diagnosed with different procedures, are often variouslyimbricated in determining ARHI, with mixed clinical findings (Gates and Mills, 2005). A growingbody of epidemiological evidence linking ARHI with late-life cognitive disorders (Panza et al.,2015a) suggested the potential for correcting hearing loss so that elders can function better alsofrom a cognitive point of view with appropriate treatment.ARHI is also a substantial marker for frailty in older age, another age-related clinical conditionfor identifying older persons at elevated risk for numerous adverse health outcomes such asfalls, institutionalization, hospitalization, disability, and death (Rodríguez-Mañas, 2013). Frailtyis as a multidimensional syndrome characterized by a nonspecific state of vulnerability, reducedmultisystem physiological reserve, and decreased resistance to stressors (Rodríguez-Mañas, 2013).Although there is no consensus regarding the operational definition of frailty, in general, twoare the most frequently used approaches: the first is the physical or “phenotypic” model offrailty, while the second is based on deficit accumulation, measured with the so called frailtyindexes, and defined as an accumulation of health-related deficits and disorders (Rodríguez-Mañas,2013). However, also psychological, cognitive and social factors are part of this multidimensionalsyndrome, with great influence on its definition and treatment. Cognition has already beensuggested as a possible component of frailty with increased risk of adverse outcomes. Therefore, theprevention of cognitive-related adverse outcomes including delirium (Eeles et al., 2012) and late-life cognitive disorders (Robertson et al., 2013; Panza et al., 2015b) may be possible also throughfrailty prevention

Episodic memory and learning rates in amyotrophic lateral sclerosis without dementia

In amyotrophic lateral sclerosis (ALS), memory deficits may be primary or secondary to executive dysfunction. We assessed episodic memory and executive function of nondemented ALS patients, comparing episodic memory profiles and learning rates of ALS patients with those of mild cognitive impairment (MCI) subjects and cognitively healthy controls (HC). In a multidisciplinary tertiary centre for motor neuron disease, 72 nondemented ALS patients, 57 amnestic MCI (aMCI), 89 single non amnestic MCI with compromised executive functions (dysexecutive MCI), and 190 HC were enrolled. They were screened using the Frontal Assessment Battery and Mini Mental State Examination. Episodic memory performances and learning rates were tested using the Rey Auditory Verbal Learning Test (RAVLT). Episodic memory dysfunction (immediate recall) was found in 14 ALS patients (19.4%). The ALS group had lower performance than HC on immediate recall, without differences in learning rate, and better performance than aMCI subjects on all RAVLT measures. Compared to dysexecutive MCI subjects, ALS patients had only better verbal learning abilities. ALS patients with executive dysfunction had a lower score on immediate and delayed recalls, verbal learning, and primacy effect than ALS patients without executive dysfunction. The immediate recall among couples of diagnostic groups differed in a statistically significant way except for the ALS/dysexecutive MCI groups. In ALS patients, episodic memory performances and learning rates appeared to be better than in aMCI subjects and similar to those with dysexecutive MCI, suggesting also a secondary functional damage due to executive impairment

Age-Related Central Auditory Processing Disorder, MCI, and Dementia in an Older Population of Southern Italy

Objective: We explored the associations of age-related central auditory processing disorder (CAPD) with mild cognitive impairment (MCI) and dementia in an older population-based cohort in Apulia, Southern Italy (GreatAGE Study). / Study Design: Cross-sectional data from a population-based study. / Setting: Castellana Grotte, Bari, Italy. / Subjects and Methods: Between 2013 and 2018, MCI, dementia, age-related CAPD (no disabling hearing loss and 65 years. / Results: The prevalences of age-related CAPD, MCI, and dementia were 14.15%, 15.79%, and 3.58%, respectively. Among the subjects with MCI and dementia, 19.61% and 42.37% had age-related CAPD. In the regressive models, age-related CAPD was associated with MCI (odds ratio, 1.50; 95% CI, 1.01-2.21) and dementia (odds ratio, 2.23; 95% CI, 1.12-4.42). Global cognition scores were positively associated with increasing SSI-ICM scores in linear models. All models were adjusted for demographics and metabolic serum biomarkers. / Conclusion: The tight association of age-related CAPD with MCI and dementia suggests the involvement of central auditory pathways in neurodegeneration, but it is not clear which is the real direction of this association. However, CAPD is a possible diagnostic marker of cognitive dysfunction in older patients

Vaccination with hemagglutinin or neuraminidase DNA protects BALB/c mice against influenza virus infection in presence of maternal antibody

<p>Abstract</p> <p>Background</p> <p>Maternal antibody is the major form of protection against disease in early life; however, its presence interferes with active immunization of offspring. In order to overcome the immunosuppression caused by maternal antibody, several immune strategies were explored in this paper using mouse model and influenza vaccines.</p> <p>Results</p> <p>The results showed that: i) when the offspring were immunized with the same vaccine as their mothers, whether inactivated or DNA vaccine, the presence of maternal antibody inhibited offspring immune response and the offspring could not be protected from a lethal influenza virus infection; ii) when the offspring, born to mothers immunized with inactivated vaccine, were immunized with NA DNA vaccine, the interference of maternal antibody were overcome and the offspring could survive a lethal virus challenge; iii) when the offspring were immunized with different DNA vaccine from that for their mothers, the interference of maternal antibody were also overcome. In addition, high-dose inactivated vaccine in maternal immunization caused partial inhibition in offspring when the offspring were immunized with HA DNA vaccine, while lower dose caused no significant immunosuppression.</p> <p>Conclusion</p> <p>To avoid the interference of maternal antibody in influenza vaccination of offspring, mothers and their offspring shall not be immunized with the same vaccine. If mothers are immunized with inactivated vaccine, NA DNA vaccine for the offspring shall be effective; and if mothers are immunized with HA (NA) DNA, NA (HA) DNA for the offspring shall be effective.</p

Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods

Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools