Reservoir hosts experiencing food stress alter transmission dynamics for a zoonotic pathogen.

Food limitation is a universal stressor for wildlife populations and is increasingly exacerbated by human activities. Anthropogenic environmental change can significantly alter the availability and quality of food resources for reservoir hosts and impact host-pathogen interactions in the wild. The state of the host's nutritional reserves at the time of infection is a key factor influencing infection outcomes by altering host resistance. Combining experimental and model-based approaches, we investigate how an environmental stressor affects host resistance to West Nile virus (WNV). Using American robins (Turdus migratorius), a species considered a superspreader of WNV, we tested the effect of acute food deprivation immediately prior to infection on host viraemia. Here, we show that robins food deprived for 48 h prior to infection, developed higher virus titres and were infectious longer than robins fed normally. To gain an understanding about the epidemiological significance of food-stressed hosts, we developed an agent-based model that simulates transmission dynamics of WNV between an avian host and the mosquito vector. When simulating a nutritionally stressed host population, the mosquito infection rate rose significantly, reaching levels that represent an epidemiological risk. An understanding of the infection disease dynamics in wild populations is critical to predict and mitigate zoonotic disease outbreaks.

Genome-wide association study for response to vaccination in Angus calves1.

BACKGROUND: Bovine respiratory disease complex (BRDC) is one of the most important sources of loss within the beef cattle industry in the USA. Steps have been taken to reduce the incidence of BRDC through vaccination. Despite the effectiveness of vaccines, large proportions of cattle still experience morbidity and mortality. Identification of genomic regions that are associated with variation in response to vaccination would allow for the selection of individuals genetically predisposed to respond to vaccination based on specific markers, while heritability and accuracy estimates would help facilitate genomic selection. This in turn may lead to selection for beef cattle herds that may have lower incidence rate of BRDC after vaccination. This study utilizes an Angus herd of more than 2000 head of cattle to identify these regions of association. RESULTS: Genome wide association studies were performed for viral neutralization antibody level and response to vaccination traits against four different viruses associated with BRDC: bovine viral diarrhea virus 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus (BHV1). A total of six 1-Mb windows were associated with greater than 1% of the genetic variance for the analyzed vaccination response traits. Heritabilities ranged from 0.08 to 0.21 and prediction accuracy ranged from 0.01 to 0.33 across 7 different vaccination traits. CONCLUSIONS: Although six 1-Mb windows were identified as associated with 1% or greater genetic variance for viral neutralization antibody level and response to vaccination traits, few genes around these windows could readily be considered candidates. This indicates the need for further functional genomic annotation, as these regions appear to be gene deserts. Traits ranged from lowly to moderately heritable, which indicated the potential for selection of individuals that are genetically pre-disposed to respond to vaccination. The relatively low amount of genetic variance accounted for by any 1-Mb window indicated that viral neutralization antibody level and response to vaccination traits are polygenic in nature. Selection for these traits is possible, but likely to be slow due to the low heritabilities and absence of markers with high genetic variation associated with them.

The vector ecology of introduced Culex quinquefasciatus populations, and implications for future risk of West Nile virus emergence in the Galápagos archipelago.

Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of West Nile virus (WNV) in the U.S.A., was first detected on the Galápagos Islands (Ecuador) in the 1980s. However, little is known of its ecology, distribution or capacity for arbovirus transmission in the Galápagos. We characterize details of lifecycle (including gonotrophic period), temporal abundance, spatial distribution, vector competence and host-feeding behaviour. Culex quinquefasciatus was detected on five islands of the Galápagos during 2006-2011. A period of 7-14 days was required for egg-adult emergence; water salinity above 5 ppt was demonstrated to hinder larval development. Blood-meal analysis indicated feeding on reptiles, birds and mammals. Assessment of WNV vector competency of Galápagos C. quinquefasciatus showed a median infectious dose of 7.41 log10 plaque-forming units per millilitre and evidence of vertical transmission (minimal filial infection rate of 3.7 per 1000 progeny). The distribution of C. quinquefasciatus across the archipelago could be limited by salt intolerance, and its abundance constrained by high temperatures. Feeding behaviour indicates potential to act as a bridge vector for transmission of pathogens across multiple taxa. Vertical transmission is a potential persistence mechanism for WNV on Galápagos. Together, our results can be used for epidemiological assessments of WNV and target vector control, should this pathogen reach the Galápagos Islands.

One Health collaborations for zoonotic disease control in Ethiopia.

Zoonotic diseases require a One Health approach for successful control and elimination due to the nature of their transmission between animals and humans. One Health recognises that the health of humans, animals, and the environment are all interconnected. Ethiopia has committed itself to controlling five prioritised zoonotic diseases (rabies, anthrax, brucellosis, leptospirosis and echinococcosis), using a One Health approach. The National One Health Steering Committee (NOHSC) provides a framework for national stakeholders to address gaps in multisectoral communication, coordination and collaboration. In addition, the NOHSC oversees the formation of several specialised disease-focused groups, referred to as 'Technical Working Groups' (TWGs). These TWGs are responsible for developing disease prevention and control strategies, as well as implementing disease-focused public health activities and providing recommendations to the NOHSC. Ethiopia's success using the One Health approach and its efficient control of zoonotic diseases will depend on the commitment of all member Ministries to support the NOHSC and TWGs, as well as to build capacity in Ethiopia's workforce and laboratories, a task supported by its many international partners.

Les zoonoses étant par nature des maladies transmissibles entre les animaux et l'homme, l'approche Une seule santé est la seule qui permette de les contrôler efficacement en vue de les éliminer. Le concept Une seule santé repose sur la prise en compte de l'interconnexion entre la santé humaine, celle des animaux et celle de l'environnement. L'Éthiopie s'est fixé pour objectif de lutter contre cinq maladies zoonotiques classées comme prioritaires (rage, fièvre charbonneuse, brucellose, leptospirose et échinococcose) en suivant une approche Une seule santé. Le comité de pilotage national Une seule santé (NOHSC) apporte un cadre permettant aux parties prenantes du pays de résoudre les problèmes de communication, de coordination et de collaboration intersectorielles. En outre, le NOHSC supervise la création de plusieurs groupes de travail techniques dédiés à des maladies spécifiques. Ces groupes de travail sont chargés d'élaborer des stratégies de prévention et de contrôle, de mettre en oeuvre des activités de santé publique axées sur ces maladies et de formuler des recommandations à l'intention du NOHSC. La réussite des efforts déployés par l'Éthiopie pour appliquer les principes Une seule santé et l'efficacité de la lutte contre les maladies zoonotiques dépendront de l'engagement des ministères concernés à soutenir le NOHSC et les groupes de travail techniques et à renforcer les capacités des ressources humaines et des laboratoires éthiopiens, tâche qui bénéficie de l'appui de nombreux partenaires internationaux.

Toda labor eficaz de control y eliminación de las enfermedades zoonóticas, por la propia naturaleza de su transmisión entre animales y personas, pasa por abordar estas patologías desde los planteamientos de Una sola salud, noción esta que parte del reconocimiento de que salud humana, animal y ambiental están siempre interconectadas. Etiopía está embarcada en el innegociable empeño de combatir cinco enfermedades zoonóticas consideradas prioritarias (rabia, carbunco bacteridiano, brucelosis, leptospirosis y equinococosis) trabajando desde la óptica de Una sola salud. El Comité Directivo Nacional de Una sola salud proporciona a los interlocutores del país un marco de referencia que sirve para subsanar las lagunas existentes en cuanto a comunicación, coordinación y colaboración entre los diversos sectores. Ese órgano, además, supervisa la formación de varios grupos especializados y centrados en una u otra enfermedad, denominados grupos de trabajo técnicos, que tienen por cometido elaborar estrategias de prevención y control de una enfermedad concreta, llevar adelante acciones de salud pública dirigidas contra ella y formular recomendaciones para el Comité Directivo. El éxito de Etiopía a la hora de aplicar los postulados de Una sola salud y de combatir eficazmente las enfermedades zoonóticas dependerá del nivel de compromiso con que todos los ministerios copartícipes presten apoyo al Comité Directivo y los grupos de trabajo técnicos y ayuden a instaurar en el país un tejido lo bastante solvente de laboratorios y recursos humanos, empresa esta en la que Etiopía cuenta con el respaldo de sus numerosos asociados internacionales.

Optimal nutrition and the ever-changing dietary landscape: a conference report.

The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects of individual nutrients at the cellular and molecular levels. This approach has appropriately expanded in recent years to become more holistic with the aim of understanding the role of nutrition in the broader context of dietary patterns. Ultimately, this approach will culminate in a full understanding of the dietary landscape-a web of interactions between nutritional, dietary, social, behavioral and environmental factors-and how it impacts health maintenance and promotion.

Epistatic interactions associated with fatty acid concentrations of beef from angus sired beef cattle.

BACKGROUND: Consumers are becoming increasingly conscientious about the nutritional value of their food. Consumption of some fatty acids has been associated with human health traits such as blood pressure and cardiovascular disease. Therefore, it is important to investigate genetic variation in content of fatty acids present in meat. Previously publications reported regions of the cattle genome that are additively associated with variation in fatty acid content. This study evaluated epistatic interactions, which could account for additional genetic variation in fatty acid content. RESULTS: Epistatic interactions for 44 fatty acid traits in a population of Angus beef cattle were evaluated with EpiSNPmpi. False discovery rate (FDR) was controlled at 5 % and was limited to well-represented genotypic combinations. Epistatic interactions were detected for 37 triacylglyceride (TAG), 36 phospholipid (PL) fatty acid traits, and three weight traits. A total of 6,181, 7,168, and 0 significant epistatic interactions (FDR < 0.05, 50-animals per genotype combination) were associated with Triacylglyceride fatty acids, Phospholipid fatty acids, and weight traits respectively and most were additive-by-additive interactions. A large number of interactions occurred in potential regions of regulatory control along the chromosomes where genes related to fatty acid metabolism reside. CONCLUSIONS: Many fatty acids were associated with epistatic interactions. Despite a large number of significant interactions, there are a limited number of genomic locations that harbored these interactions. While larger population sizes are needed to accurately validate and quantify these epistatic interactions, the current findings point towards additional genetic variance that can be accounted for within these fatty acid traits.

Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism.

The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches.

Health status and disease burden of unaccompanied asylum-seeking adolescents in Bielefeld, Germany: cross-sectional pilot study.

OBJECTIVE: This exploratory pilot study aimed to investigate the physical and mental disease burden of unaccompanied asylum-seeking adolescents arriving in Bielefeld, a medium-size city in Germany. METHODS: A cross-sectional survey with purposive sampling of 102 unaccompanied asylum-seeking adolescents aged 12-18 years was performed. Information on general health status, selected infectious and non-communicable diseases, iron deficiency anaemia and mental illness was collected during routine check-up medical examinations upon arrival in Bielefeld, Germany. The data were analysed using descriptive statistics. RESULTS: The analysis revealed a complex disease burden with a high prevalence of infections (58.8%), mental illness (13.7%) and iron deficiency anaemia (17.6%) and a very low prevalence of non-communicable diseases (<2.0%). One in five of the refugees were infected with parasites. Whilst sub-Saharan Africans showed the highest prevalence of infections (86.7%), including highest prevalences of parasites (46.7%), West Asians had the highest prevalence of mental disorders (20.0%). Overall, the disease burden in females was higher. CONCLUSION: A thorough medical and psychological screening after arrival is highly recommended to reduce the individual disease burden and the risk of infection for others. This promotes good physical and mental health, which is needed for successful integration into the receiving society. Barriers to health service access for unaccompanied asylum-seeking adolescents need to be lowered to allow need-specific health care and prevention.

Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem.

Fecal microbiota transplantation has gathered much attention due to its high efficacy in resolving recurrent Clostridium difficile infection. Until today, it is recognized as a safe procedure without any severe side effects. Patients with impaired conscious states suffering from recurrent episodes of aspiration are at increased risk by endoscopic interventions needed during standard approaches for fecal microbiota transplantation application.Here, we illustrate the case of a tetraplegic patient undergoing fecal microbiota transplantation due to his fifth recurrent episode of Clostridium difficile infection using a self-advancing nasal jejunal feeding tube as effective minimal-invasive option of fecal microbiota transplantation application. Persistent aggravation of arterial hypertension, which developed post-intervention in this patient, could be interpreted as a hitherto unknown side effect of fecal microbiota transplantation in this setting. Moreover, this is a further hint for a link between the intestinal microbiome and arterial hypertension in general.

Potential role of ATP-binding cassette transporters against acaricides in the brown dog tick Rhipicephalus sanguineus sensu lato.

ATP-binding cassette (ABC) transporters have been shown to be involved in pesticide detoxification in arthropod vectors and are thought to contribute to the development of drug resistance. Little is currently known about the role they play in ticks, which are among the more important vectors of human and animal pathogens. Here, the role of ABC transporters in the transport of fipronil and ivermectin acaricides in the tick Rhipicephalus sanguineus (Ixodida: Ixodidae) was investigated. Larvae were treated with acaricide alone and acaricide in combination with a sub-lethal dose of the ABC transporter inhibitor cyclosporine A. The LC50 doses and 95% confidence intervals (CIs) estimated by mortality data using probit analysis were 67.930 p.p.m. (95% CI 53.780-90.861) for fipronil and 3741 p.p.m. (95% CI 2857-4647) for ivermectin. The pre-exposure of larvae to a sub-lethal dose of cyclosporine A reduced the LC50 dose of fipronil to 4.808 p.p.m. (95% CI 0.715-9.527) and that of ivermectin to 167 p.p.m. (95% CI 15-449), which increased toxicity by about 14- and 22-fold, respectively. The comparison of mortality data for each separate acaricide concentration showed the synergic effect of cyclosporine A to be reduced at higher concentrations of acaricide. These results show for the first time a strong association between ABC transporters and acaricide detoxification in R.sanguineus s.l.

Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer's Disease.

BACKGROUND: Lecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to amyloid-beta protein protofibrils. In phase 3 development, lecanemab has been shown to reduce markers of amyloid in early Alzheimer's disease and reduce decline on clinical endpoints of cognition and function at 18 months. OBJECTIVES: To describe the health-related quality-of-life (HRQoL) results from Clarity AD which were exploratory outcomes in this trial. DESIGN: Clarity AD was an 18-month, multi-center, double-blind, phase 3 trial. SETTING: Early Alzheimer's disease. PARTICIPANTS: Individuals 50-90 years of age with a diagnosis of mild cognitive impairment or mild dementia due to Alzheimer's disease and positron emission tomography or cerebrospinal fluid evidence of cerebral amyloid accumulation. INTERVENTION: Placebo or lecanemab 10-mg/kg IV biweekly. MEASUREMENTS: HRQoL was measured at baseline and every 6 months using the European Quality of Life-5 Dimensions (EQ-5D-5L; by subject) and Quality of Life in AD (QOL-AD; by subject and proxy). Study partner burden was measured using the Zarit Burden Interview (ZBI). RESULTS: A total of 1795 participants were enrolled (lecanemab:898; placebo:897). At month 18, adjusted mean change from baseline in EQ-5D-5L and QOL-AD by subject showed 49% and 56% less decline, respectively. QOL-AD rated by study partner as proxy resulted in 23% less decline. ZBI adjusted mean change from baseline at 18 months resulted in 38% less increase of care partner burden. Individual HRQoL test items and dimensions also showed lecanemab benefit. CONCLUSIONS: Lecanemab was associated with a relative preservation of HRQoL and less increase in caregiver burden, with consistent benefits seen across different quality of life scales and within scale subdomains. These benefits provide valuable patient reported outcomes which, together with previously reported benefits of lecanemab across multiple measures of cognition, function, disease progression, and biomarkers, demonstrate that lecanemab treatment may offer meaningful benefits to patients, care partners, and society.

Probing the high momentum component of the deuteron at high Q2.

The (2)H(e,e'p)n cross section at a momentum transfer of 3.5 (GeV/c)(2) was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a function of the neutron recoil angle θ(nq) and to extract missing momentum distributions for fixed values of θ(nq) up to 0.55 GeV/c. In the region of 35°≤θ(nq)≤45° recent calculations, which predict that final-state interactions are small, agree reasonably well with the experimental data. Therefore, these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electrodisintegration.

Fine-scale spatial and temporal population genetics of Aedes japonicus, a new US mosquito, reveal multiple introductions.

The newly introduced mosquito Aedes japonicus has expanded from its original range in Northeastern Asia to 29 US states (including Hawaii) plus Canada and northern Europe. Our objectives were to test an earlier hypothesis of multiple introductions of this species to the Northeastern US and evaluate putative temporal changes in genetic makeup. Using a panel of seven microsatellite loci, we confirmed the existence of two abundant genetic forms in specimens originally collected in 1999-2000 (F(ST) value based on microsatellite data = 0.26) that matches the disjunctive distribution of mitochondrial haplotypes. To examine the distribution of the two genetic 'types' across Pennsylvania we created a fine-scale genetic map of Ae. japonicus using 439 specimens collected from 54 Pennsylvania counties in 2002-2003. We also made direct comparisons between collections in 1999-2000 and new collections made in 2004-2005 obtained from the same areas in the northeastern US. We observed that the strong association between mtDNA haplotype and microsatellite signature seen in 1999-2000 had weakened significantly by 2002 across Pennsylvania, a trend continued to some extent in 2004-2005 in PA, NJ, and NY, indicating that once easily distinguishable separate introductions are merging. The two expanding genetic forms create a complex correlation between spatial and genetic distances. The existence of multiple introductions would be obscured without sampling early and across time with highly polymorphic molecular markers. Our results provide a high-resolution analysis of the spatial and temporal dynamics of a newly introduced disease vector and argue that successive introductions may be a common pattern for invasive mosquitoes.

Probing quark-gluon interactions with transverse polarized scattering.

We have extracted QCD matrix elements from our data on doubly polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element d˜2, which arises strictly from quark-gluon interactions, to be unambiguously nonzero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.

Expression and localization of stanniocalcin 1 in swine ovary.

Stanniocalcin 1 (STC 1) is a glycoprotein involved in mineral homeostasis and was first identified in fish. Its mammalian homologue has been implicated in the regulation of various biological processes, including angiogenesis and steroidogenesis both of which are fundamental events in ovarian function. Interestingly, the highest level of STC 1 expression in mammals occurs in ovarian tissue but no information is available on swine species. Therefore, the present study was undertaken to investigate the expression and the immunolocalization of STC 1 in swine ovary. In addition, we evaluated whether swine granulosa cells synthesize STC 1 and its possible modulation by hypoxia, a physiological condition in ovarian follicle growth. Our data show STC 1 for the first time in swine ovary; moreover, we demonstrate STC 1 production by granulosa cells, both in basal condition and in response to oxygen deprivation. The latter is suggestive of a potential modulatory role for STC 1 in hypoxia-driven angiogenesis.

[Serological and sociodemographic differences in HBV-patients with and without migration background]. / Serologische und soziodemografische Unterschiede bei HBV-Patienten mit und ohne Migrationshintergrund.

BACKGROUND: It is estimated that 0.5 to 1 % of the total German population is chronically infected with the hepatitis B virus (HBV). This means that approximately 500 000 chronically infected individuals live in Germany and that around 10 % of them need antiviral treatment. According to an epidemiological calculation, around 42 % of them are migrants. The aim of our study was to gather more information on socio-demographic features of HBV patients and the sero-epidemological status and treatment of these patients. METHODS: Data collection was carried out in hepatological practices and outpatient clinics in Germany. We collected data from adult patients with chronic hepatitis B by studying their patient records and interviewing the patients and the responsible physicians. RESULTS: Data of 160 patients from 20 different facilities could be collected. 57.5 % of them were male, mean age was 43.7 (range: 19 - 81 years). 61 (38.1 %) were Germans without a migration background, 82 (51.3 %) were first generation migrants and 17 (10.6 %) second generation migrants. We detected significant differences in the level of professional training and employment status between participants with and without migration background. Only 3 % of migrants had a university degree compared to 36.1 % of patients without migration background. In addition, more migrants were unemployed (38.9 % vs. 19.6 %). From all participants 72.4 % were HBeAg-negative. 111 (69.4 %) of all patients received a hepatitis B specific treatment at the time they were interviewed, most of them adefovir (41.5 %) or lamivudin (35.4 %) alone. DISCUSSION: The estimated high HBV prevalence in migrants from countries with intermediate to high prevalence is reflected in the high number of patients with migration background in hepatological practices and outpatient clinics. To avoid further HBV infections in this population group and to reduce the HBV prevalence in Germany, the effect of further interventions, like a general HBV screening of all new incoming migrants from intermediate or high endemic areas, their vaccination and if necessary treatment, have to be tested.

New insights into the biology, diagnosis and immune response to Dirofilaria repens in the canine host.

Dogs are the primary host for Dirofilaria repens, therefore it is mandatory to accurately diagnose the canine infection and to expand our current knowledge on parasite biology and the immune response of the infected host for a better prevention.Thus, the aim of the present study was to provide new insights from experimental infections of dogs with D. repens, focusing on the evaluation of: 1) the pre-patent period and 2) the antibody response against D. repens somatic antigens and against the Wolbachia endosymbiont. Briefly, on Day 0, twenty purpose-bred Beagle dogs were experimentally infected with 50 infective larvae (L3) of D. repens. Starting from Day 58 until the last day of the study (Day 281), blood samples were collected on a monthly basis for detection of antibodies against D. repens (Dr) and recombinant Wolbachia surface protein (rWSP) by non-commercial IgG-ELISAs. Additional samples were collected on Days 220, 245 and 281 for the detection of microfilariae (mff) using the modified Knott's test and biomolecular analysis, following two PCR protocols: Gioia et al. (2010; protocol A) and Rishniw et al. (2006- protocol B). The results were analysed by univariate statistical analyses using 2×2 contingency tables and K Cohen was calculated to assess the agreement among all the diagnostic techniques. Overall, the outcome of the study revealed that out of the 20 dogs experimentally infected with D. repens, 16 (80 %) were microfilaraemic, 17 (85 %) were positive at DNA detection in the blood, 18 (90 %) had D. repens antibodies and 16 (80 %) had Wolbachia antibodies on the last day of the study. The overall k agreement between Knott's and PCR protocol B was 0.442 (P=0.0001) and increased throughout the study, reaching 0.828 (P=0.0001) on Day 281. To the authors knowledge, this is only the second study reporting antibody response to D. repens somatic antigen in experimentally infected dogs. ELISA results showed that an antibody response develops before the onset of patency, and steadily increases with time. Results would suggest that the development of an immunological response to infection could lead to application in epidemiological studies, risk assessment and as an aid in the diagnostic approach in dogs, in particular for early infections without mff.

New insights into the biology, diagnosis and immune response to Dirofilaria repens in the canine host.

Dogs are the primary host for Dirofilaria repens, therefore it is mandatory to accurately diagnose the canine infection and to expand our current knowledge on parasite biology and the immune response of the infected host for a better prevention.Thus, the aim of the present study was to provide new insights from experimental infections of dogs with D. repens, focusing on the evaluation of: 1) the pre-patent period and 2) the antibody response against D. repens somatic antigens and against the Wolbachia endosymbiont. Briefly, on Day 0, twenty purpose-bred Beagle dogs were experimentally infected with 50 infective larvae (L3) of D. repens. Starting from Day 58 until the last day of the study (Day 281), blood samples were collected on a monthly basis for detection of antibodies against D. repens (Dr) and recombinant Wolbachia surface protein (rWSP) by non-commercial IgG-ELISAs. Additional samples were collected on Days 220, 245 and 281 for the detection of microfilariae (mff) using the modified Knott's test and biomolecular analysis, following two PCR protocols: Gioia et al. (2010; protocol A) and Rishniw et al. (2006- protocol B). The results were analysed by univariate statistical analyses using 2 × 2 contingency tables and K Cohen was calculated to assess the agreement among all the diagnostic techniques. Overall, the outcome of the study revealed that out of the 20 dogs experimentally infected with D. repens, 16 (80 %) were microfilaraemic, 17 (85 %) were positive at DNA detection in the blood, 18 (90 %) had D. repens antibodies and 16 (80 %) had Wolbachia antibodies on the last day of the study. The overall k agreement between Knott's and PCR protocol B was 0.442 (P = 0.0001) and increased throughout the study, reaching 0.828 (P = 0.0001) on Day 281. To the authors knowledge, this is only the second study reporting antibody response to D. repens somatic antigen in experimentally infected dogs. ELISA results showed that an antibody response develops before the onset of patency, and steadily increases with time. Results would suggest that the development of an immunological response to infection could lead to application in epidemiological studies, risk assessment and as an aid in the diagnostic approach in dogs, in particular for early infections without mff.

The Future of Anti-Amyloid Trials.

The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer's disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer's Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Critical factors that have emerged in studies of anti-amyloid monoclonal antibody therapies include developing a better understanding of the specific amyloid species targeted by different antibodies, advancing our insight into the mechanism by which those antibodies may reduce pathology, implementing more comprehensive repertoires of biomarkers into trials, and identifying appropriate doses. Studies suggest that Amyloid-Related Imaging Abnormalities - effusion type (ARIA-E) are a manageable safety concern and that caution should be exercised before terminating studies based on interim analyses. The Task Force concluded that opportunities for developing effective treatments include developing new biomarkers, intervening in early stages of disease, and use of combination therapies.