The Control Program of Brucellosis by the Iranian Veterinary Organization in Industrial Dairy Cattle Farms.

Brucellosis is a zoonotic infection in livestock that induces a major public health concern in developing countries, including Iran. Despite the efforts of the Iranian veterinary organization (IVO) to control brucellosis, it is still prevalent in domestic animals. In this regard, the present study aimed to evaluate the efficiency of the control strategy used by the IVO in infected herds on serological, cultural, and molecular methods. For this purpose, blood specimens were sampled from a total of 8750 vaccinated dairy cattle in two Brucella-infected farms. These farms were recognized as positive for Brucella by a screening program. Sera were evaluated by the Rose Bengal Plate Test and Wright test analysis. Positive dairy cattle were slaughtered under IVO supervision. The remaining cattle were evaluated every 3 weeks and positive animals were slaughtered. This procedure continued until the remaining animals revealed three successive negative responses in serological tests. Several lymph nodes and milk samples were collected from 164 seropositive cattle and subjected to bacterial isolation and confirmation by Bruceladder-polymerase chain reaction. Brucella melitensis biovar 1 and RB51 vaccine strains were recovered from milk and lymph node samples, respectively. Shedding of B. melitensis in the milk of vaccinated cows is a serious problem resulting in the further spread of brucellosis. The policy of "test and slaughter" performed on infected dairy cattle farms showed their usefulness for the control of brucellosis outbreaks. For the uncontrolled spread of brucellosis in Iran, effective control of bovine brucellosis required several serological surveillances to identify infected herds, eradication of the reservoirs, and vaccination of young heifers with RB51.

Evaluation of in vitro Anti-Brucella Activity and Chemical Composition of Different Geographically Distinct Propolis from Iran.

Brucellosis is one of the most important zoonotic diseases in many regions worldwide. This study aimed to investigate the antimicrobial properties of hydro-ethanolic extracts of propolis (EEP) samples collected from six different regions of Iran against five Brucella melitensis (B. melitensis) clinical isolates causing human brucellosis and an antibiotic-resistant B. abortus vaccinal strain (RB51). Brucella clinical isolates were first carefully identified using conventional molecular typing and Brucella bio-typing methods. Different Brucella strains were then confronted with EEPs using the disk-diffusion agar method to evaluate the antimicrobial activity of each propolis extract. Chemical composition of EEPs was then determined using HPLC-DAD, and the main phenolic compounds were quantified. It was found that all EEPs displayed significant antimicrobial activities against Brucella strains, though to varying extents. All tested clinical strains were susceptible to different EEPs with inhibition zones ranging from 18 to 38 mm diameter. Interestingly, the RB51 vaccine strain was more susceptible to EEP6 (from Markazi province), compared to conventional antibiotics used in the treatment of brucellosis. Substantial differences observed in EEP antimicrobial activity could be due to their distinct botanical origins and chemical compositions as confirmed by our HPLC analysis. The promising inhibitory effect of some propolis preparations against a broad spectrum of Brucella strains points to the need for further studies in the context of systematic clinical investigations and opens up the way for the development of natural complements in support of conventional antibiotic therapy.

The PaleoArchiNeo (PAN) human brain atlas: A dataset on a standard neuroanatomical MRI template following a phylogenetic approach.

Cortical atlases provide consistent divisions of the human cortex into areas that have common structural as well as meaningful and distinctive functional characteristics. They constitute a fundamental tool to study and quantify changes in healthy and pathological states. Historically, the most widely used atlases follow the cytoarchitecture described by Brodmann and/or the myeloarchitectonic characteristics described by Vogt-Vogt. These histological approaches have since been combined to the standard anatomical nomenclature of gyri and sulci, referring to the corresponding cytoarchitectonic area(s) present in a gyrus, when applicable or necessary (e.g. area 4 of Brodmann in the pre-central gyrus). More recently, common functional features depicted by resting state functional MRI have guided the division of the cortex into functional regions of interest. However, to date, there are no human MRI atlases that divide the cortex considering the common evolutionary changes experienced by the mammalian cortex. Hence, the present dataset describes the PaleoArchiNeo (PAN) Human Brain, a voxel-based atlas that divides the human cortex into five regions of interest (ROIs) following a phylogenetic approach: 1- archicortex, 2- paleocortex, 3- peri-archicortex, 4- proisocortex, 5- neocortex, and thirty neocortical sub-ROIs that follow the gyral Terminologia Anatomica.The masks of the ROIs and sub-ROIs were segmented on the T1-weighted MNI ICBM 152 2009c symmetric average brain MRI model, the latest version of the most widely used standard brain template. The segmentations have been performed manually by anatomist experts, following the MRI anatomical landmarks that have been previously described, correlated, and validated with histology by other groups.

Molecular Survey of Brucella melitensis Field Isolates using Sequence-Based PCR of Outer Membrane Protein 31.

Sequence-based Polymerase Chain Reaction (PCR) has been introduced as an effective and reliable method for bacterial strain typing, which could provide a reliable typing approach for clinical laboratories. This study aimed to describe the reproducibility and performance of the Outer Membrane Protein 31 (Omp31)-based PCR, as a molecular genotyping tool for Brucella melitensis (B. melitensis) typing. The 31 KD outer-membrane protein of Brucella, which encodes the Omp31 gene, can be applied as an antigen to diagnose brucellosis. For this purpose, 146 samples were taken from human blood samples, bovine and camel lymph nodes, as well as sheep and goat aborted fetuses, including fetal kidney, abomasum, liver, lung, spleen, and heart for bacteriological investigation. The molecular detection of the Omp31 and IS711 genes was performed using the isolated B. melitensis (n=14). The sequencing of the Omp31 gene of B. melitensis in the Iranian field isolates was also performed for the whole gene sequencing. The homology of all sequences was then checked with the reported National Center for Biotechnology Information sequences using a basic local alignment search tool for the nucleotide diversity evaluation. The findings revealed that B. melitensis isolates were recovered from 14 examined cases and confirmed by the IS711-based PCR with a PCR product of 731 bp. Moreover, 14 Iranian B. melitensis sequences clustered together as a monophyletic grouping with bootstrap support of 63, and they were closely related to the B. melitensis reference isolates. This Omp31-based phylogenetic placement strongly indicates the monophyletic origin of the Iranian B. melitensis in different animals and human hosts.

Identification of Main Brucella species Implicated in Ovine and Caprine Abortion Cases by Molecular and Classical Methods.

Brucellosis is recognized as a major public health concern leading to critical economic losses in livestock animals. The present study assessed Brucella spp. isolated from aborted ovine and caprine fetuses in different parts of Iran between 2016 and 2019. It used classic and molecular methods in order to determine the Brucella species carrying higher risks of abortion complications in these animals. A total of 189 samples from 35 cases/case series from milk (16 sheep, and 8 goats), 19 abomasum content (sheep), and 146 aborted fetuses (116 sheep, and 30 goats) were bacteriologically examined. Subsequently, the resultant Brucella isolates were further characterized by phenotypic and molecular approaches. The multiplex Polymerase chain reaction (PCR) (Bruce-ladder) and IS711-based PCR were performed on all the extracted DNA to evaluate the presence of Brucella spp. As suggested by the obtained results, all recovered isolates from ovine and caprine abortion samples were either B. melitensis or B. abortus. An issue of concern was the implication of B. melitensis vaccine strain Rev1 in a small portion of sheep and goat abortion cases. Despite the recent B. abortus burden in ovine, aborted cases were predominantly associated with B. melitensis infections in both ovine and caprine, and B. melitensis biovar 1 was responsible for the majority of studied cases. These data and the techniques implemented in the present study can shed light on the level of implication of different Brucella species in ovine and caprine abortion in Iran. The present study identified Brucella agents responsible for abortion in small ruminants at the biovar level. Therefore, it provides precious information for future control programs and vaccination strategies in Middle Eastern regions.

Role of Brucella abortus Biovar 3 in the Outbreak of Abortion in a Dairy Cattle Herd Immunized with Brucella abortus Iriba Vaccine.

Bovine brucellosis is a widespread zoonosis caused by Brucella abortus. The disease is prevalent nationwide in Iran and is on an increasing trend among humans and livestock. The eradication of brucellosis is challenging and requires control policies at both national and regional levels. Regarding this, the aim of the current study was to evaluate if Brucella is implicated in an abortion outbreak that occurred in a dairy cattle herd, in Shahre Rey, Tehran province, Iran, after vaccination with B. abortus Iriba vaccine. The research context was a dairy cattle farm with 2,000 animals located in Shahre Rey. This farm was Brucella-free based on the results of two serological tests performed one month before vaccination. After the incidence of the first case of abortion following vaccination, serodiagnosis revealed a seropositive reaction in 30 non-pregnant cows and 19 pregnant cows that aborted later. Bacteriology and molecular typing facilitated the identification of 16 isolates of B. abortus biovar 3 from the aborted animals. None of the isolates were confirmed as B. abortus Iribavaccine strain. The results confirmed that B. abortus biovar 3 was the most prevalent biovar in the cattle of Iran. The source and time of infection in the current study were not detected most likely due to the low biosecurity level in the farm (e.g., uncontrolled introduction of the agents via humans, infected animals, semen, and vectors). In endemic countries, the serodiagnosis of brucellosis alone is not sufficient and has to be accompanied by isolation and molecular diagnosis. In addition, it is important to evaluate the presence of B. abortus in bovine semen and vectors.

Neural Correlates of Evidence and Urgency During Human Perceptual Decision-Making in Dynamically Changing Conditions.

Current models of decision-making assume that the brain gradually accumulates evidence and drifts toward a threshold that, once crossed, results in a choice selection. These models have been especially successful in primate research; however, transposing them to human fMRI paradigms has proved it to be challenging. Here, we exploit the face-selective visual system and test whether decoded emotional facial features from multivariate fMRI signals during a dynamic perceptual decision-making task are related to the parameters of computational models of decision-making. We show that trial-by-trial variations in the pattern of neural activity in the fusiform gyrus reflect facial emotional information and modulate drift rates during deliberation. We also observed an inverse-urgency signal based in the caudate nucleus that was independent of sensory information but appeared to slow decisions, particularly when information in the task was ambiguous. Taken together, our results characterize how decision parameters from a computational model (i.e., drift rate and urgency signal) are involved in perceptual decision-making and reflected in the activity of the human brain.

Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development.

Vaccination is one of the most important prevention tools providing protection against infectious diseases especially in children below the age of five. According to estimates, more than 5 million lives are saved annually by the implementation of six standard vaccines, including diphtheria, hepatitis B, Haemophilus influenza type b, polio, tetanus and yellow fever. Despite these efforts, we are faced with challenges in developing countries where increasing population and increasing disease burden and difficulties in vaccine coverage and delivery cause significant morbidity and mortality. Additionally, the high cost of these vaccines is also one of the causes for inappropriate and inadequate vaccinations in these regions. Thus, developing cost-effective vaccine strategies that could provide a stronger immune response with reduced vaccination schedules and maximum coverage is of critical importance. In last decade, different approaches have been investigated; among which live bacterial vaccines have been the focus of attention. In this regard, probiotic lactic acid bacteria have been extensively studied as safe and effective vaccine candidates. These microorganisms represent the largest group of probiotic bacteria in the intestine and are generally recognised as safe (GRAS) bacteria. They have also attracted attention due to their immunomodulatory actions and their effective role as novel vaccine adjuvants. A significant property of these bacteria is their ability to mimic natural infections, while intrinsically possessing mucosal adjuvant properties. Additionally, as live bacterial vaccines are administered orally or nasally, they have higher acceptance and better safety, but also avoid the risk of contamination due to needles and syringes. In this review, we emphasise the role of probiotic Lactobacillus strains as putative oral vaccine carriers and novel vaccine adjuvants.

A Case of Identity Confirmation of Brucella abortus S99 by Phage Typing and PCR Methods.

Brucellosis is a zoonotic infection that is associated with fever in humans and abortion in animals. The agent of this disease is a facultative intracellular gram-negative coccobacillus called Brucella. There are six classic species, including B. abortus, B. melitensis, B. suis, B. canis, B. neotomae, and B. ovis. In recent years, four new species have been reported, including Brucella ceti, B. microti, B. pinnipedialis, and B. inopinata. Human disease causes hygienic and economic losses, including inactivity of workforces in the community and high cost of treatment. The disease also causes catastrophic losses in the livestock industry. There is no effective vaccine against human brucellosis. Hence, attempts to prevent human infection with Brucella are focused on preventative measures, including control of infection in livestock, which lead to a reduction in its incidence in humans. The common methods for diagnosis of this disease are serologic methods including Rose Bengal, Wright -2 ME and the ring test. B. abortus strain S99 is used to produce these diagnostic antigens. The production of these antigens requires the presence of a well-characterized seed with full identity. The aim of this work was confirmation of the identity of B. abortus S99 by phage typing, AMOS and multiplex PCR techniques. Therefore, it is essential to carry out the identification of the strains used as seed for the production of the brucellosis diagnostic antigens. In this project, B. abortus strain 99 was supplied by the bacterial collection of the Brucellosis Department of Razi Vaccine and Serum Research Institute. Then, the main aim of the present study was the confirmation of the seed identity by doing the tests through the standard phage typing method, AMOS PCR and multiplex PCR (Brucladder) methods. Results were in support of the identity of the studied strain, and the molecular methods could also be used as the sensitive approaches for validation of antigenic seed.

Comparison of Multiple Sclerosis Cortical Lesion Types Detected by Multicontrast 3T and 7T MRI.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

Predictive model of spread of Parkinson's pathology using network diffusion.

Growing evidence suggests that a "prion-like" mechanism underlies the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). We extend and tailor previously developed quantitative and predictive network diffusion model (NDM) to PD, by specifically modeling the trans-neuronal spread of alpha-synuclein outward from the substantia nigra (SN). The model demonstrated the spatial and temporal patterns of PD from neuropathological and neuroimaging studies and was statistically validated using MRI deformation of 232 Parkinson's patients. After repeated seeding simulations, the SN was found to be the most likely seed region, supporting its unique lynchpin role in Parkinson's pathology spread. Other alternative spread models were also evaluated for comparison, specifically, random spread and distance-based spread; the latter tests for Braak's original caudorostral transmission theory. We showed that the distance-based spread model is not as well supported as the connectivity-based model. Intriguingly, the temporal sequencing of affected regions predicted by the model was in close agreement with Braak stages III-VI, providing what we consider a "computational Braak" staging system. Finally, we investigated whether the regional expression patterns of implicated genes contribute to regional atrophy. Despite robust evidence for genetic factors in PD pathogenesis, NDM outperformed regional genetic expression predictors, suggesting that network processes are far stronger mediators of regional vulnerability than innate or cell-autonomous factors. This is the first finding yet of the ramification of prion-like pathology propagation in Parkinson's, as gleaned from in vivo human imaging data. The NDM is potentially a promising robust and clinically useful tool for diagnosis, prognosis and staging of PD.

Network connectivity determines cortical thinning in early Parkinson's disease progression.

Here we test the hypothesis that the neurodegenerative process in Parkinson's disease (PD) moves stereotypically along neural networks, possibly reflecting the spread of toxic alpha-synuclein molecules. PD patients (n = 105) and matched controls (n = 57) underwent T1-MRI at entry and 1 year later as part of the Parkinson's Progression Markers Initiative. Over this period, PD patients demonstrate significantly greater cortical thinning than controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical thinning is correlated to connectivity (measured functionally or structurally) to a "disease reservoir" evaluated by MRI at baseline. The atrophy pattern in the ventral frontal lobes resembles one described in certain cases of Alzheimer's disease. Our findings suggest that disease propagation to the cortex in PD follows neuronal connectivity and that disease spread to the cortex may herald the onset of cognitive impairment.