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

Plasma Inflammatory Cytokines Are Elevated in ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which leads to death in a median time of 2–3 years. Inflammation has been claimed important to the ALS pathogenesis, but its role is still not well-characterized. In the present study, a panel of five cytokines (IL-2, IL-6, IL-10, IFN-gamma, and TNF-alpha)measured in plasma has been investigated in ALS. These biomarkers of inflammation were measured in a population-based cohort of 79 patients with ALS and 79 age- and sex-matched healthy controls using the Bio-Plex technology (Bio-Rad). All the five cytokines were significantly increased in plasma samples of patients compared with controls (p < 0.0001), with IL-6 having the highest median concentration (10.11 pg/ml) in the ALS group. Furthermore, IL-6 was the plasma cytokine with the highest discrimination ability between patients and controls according to the receiver operating characteristic analysis (area under the curve = 0.93). At a cut-off point of 5.71 pg/ml, it was able to classify patients and controls with 91% of sensitivity and 87% of specificity. In the ALS group, plasma IL-6 concentration correlated with demographic (age: rs = 0.25, p = 0.025) and clinical (revised ALS Functional Rating Scale at evaluation: rs = −0.32, p = 0.007; Manual Muscle Testing: rs =−0.33, p=0.004; progression: rs=0.29, p=0.0395) parameters. In line with previous studies, our results confirm that inflammatory cytokines are elevated in ALS, supporting a possible role of inflammation in disease mechanism and progression. However, the precise role of inflammation in ALS needs to be further investigated on larger samples and with more mechanistic studies

Telemedicine for Delivery of Care in Frontotemporal Lobar Degeneration during COVID-19 Pandemic: Results from Southern Italy

Background: The COVID-19 pandemic is changing clinical practice in neurology, after the governments decided the introduction of social distancing and interruption of medical non-emergency services in many countries. Teleneurology is an effective tool for the remote evaluation of patients but its adoption for frontotemporal lobar dementia (FTD) is in a preliminary stage. Objective: We evaluated multidisciplinary assessment of patients with FTD using telehealth during the COVID-19 pandemic. Methods: All patients received a diagnosis of FTD during 2018-2019 according to international criteria. A structured questionnaire and Clinical Dementia Rating Scale (CDR)-FTD were used by the neurologist with patients and/or caregivers. Index symptoms of COVID-19 infection were searched. Results: Twenty-eight clinical interviews were completed with caregivers and four with both patients/caregivers. Most patients and caregivers were satisfied with the neurological interview and expressed their willingness to continue to be included in remote evaluation programs (90%). Fifty percent of patients experienced significant worsening of clinical picture and quality of life since the start of social distancing. The CDR-FTD scale revealed a significant worsening of behavior (p = 0.01) and language functions (p = 0.009), compared to the last in-person evaluation at the center. One patient presented index symptoms of COVID-19 infection and was confirmed to be positive for COVID-19 with pharyngeal swab. Conclusion: The study was conducted in Italy, one of the countries hit particularly hard by the COVID-19 pandemic, with interruption of all non-emergency medical services. Our study indicates that telemedicine is a valid tool to triage patients with FTD to increase practice outreach and efficiency

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