Primary angiitis of the CNS and ANCA-associated vasculitis: from pathology to treatment.

Vasculitis of the central nervous system can be a localized process, such as primary angiitis of the central nervous system (PACNS), or systemic vasculitis, such as ANCA-associated vasculitis (AAV). Since both conditions share neurological manifestations, the following review will discuss the neurological aspects of both. This review aims to provide a comprehensive comparison of the pathogenesis, clinical manifestation and assessment, diagnostic workup, and treatment protocol for both PACNS and AAV with central nervous system involvement. To provide a comprehensive comparison and update, a literature review was conducted using PubMed and Ovid databases (Embase and Medline). Then, the references were retrieved, screened, and selected according to the inclusion and exclusion criteria. PACNS and AAV share similarities in clinical presentation and neurological symptoms, especially in terms of headache, focal deficits, and cognitive impairment. Additionally, both conditions may exhibit similarities in laboratory and radiological findings, making brain biopsy the gold standard for differentiation between the two conditions. Moreover, the treatment protocols for PACNS and AAV are nearly identical. Comparing PACNS and AAV with CNS involvement highlights the similarities in clinical presentation, radiological findings, and treatment protocols between the two conditions. Further research should focus on establishing a practical diagnostic protocol.

Challenges in Local Allergic Rhinitis Diagnosis, Management, and Research: Current Concepts and Future Perspectives.

Local allergic rhinitis (LAR) is diagnosed based on the presence of clinical symptoms such as rhinorrhea, sneezing, and nasal itching using negative skin prick testing and serum IgE assessment. Several novel studies have shown that it is possible to use the assessment of nasal sIgE (specific immunoglobulin E) secretion as an additional diagnostic criterion for local allergic rhinitis. Additionally, allergen immunotherapy is a promising-albeit still not fully assessed and evaluated-future method of managing patients with LAR. In this review, the historical background, epidemiology, and main pathophysiological mechanisms of LAR shall be presented. Additionally, we address the current state of knowledge based on selected articles regarding the assessment of the local mucosal IgE presence in response to exposure to such allergens as mites, pollen, molds, and others. The impact of LAR on quality of life as well as the possible options of management (including allergen immunotherapy (AIT), which showed promising results) will then be presented.

Angiotensin II type-2-receptor stimulation ameliorates focal and segmental glomerulosclerosis in mice.

Podocyte damage and loss are the early event in the development of focal segmental glomerulosclerosis (FSGS). Podocytes express angiotensin II type-2-receptor (AT2R), which may play a key role in maintaining kidney integrity and function. Here, we examined the effects of AT2R deletion and AT2R agonist compound 21 (C21) on the evolution of FSGS. FSGS was induced by adriamycin (ADR) injection in both male wild-type (WT) and AT2R knockout (KO) mice. C21 was administered to WT-FSGS mice either one day before or 7 days after ADR (Pre-C21 or Post-C21), using two doses of C21 at either 0.3 (low dose, LD) or 1.0 (high dose, HD) mg/kg/day. ADR-induced FSGS was more severe in AT2RKO mice compared with WT-FSGS mice, and included profound podocyte loss, glomerular fibrosis, and albuminuria. Glomerular cathepsin L expression increased more in AT2RKO-FSGS than in WT-FSGS mice. C21 treatment ameliorated podocyte injury, most significantly in the Pre C21-HD group, and inhibited glomerular cathepsin L expression. In vitro, Agtr2 knock-down in mouse podocyte cell line given ADR confirmed the in vivo data. Mechanistically, C21 inhibited cathepsin L expression, which protected synaptopodin from destruction and stabilized actin cytoskeleton. C21 also prevented podocyte apoptosis. In conclusion, AT2R activation by C21 ameliorated ADR-induced podocyte injury in mice by the inhibition of glomerular cathepsin L leading to the maintenance of podocyte integrity and prevention of podocyte apoptosis.

Healthcare-acquired coronavirus disease 2019 (COVID-19) is less symptomatic than community-acquired disease among healthcare workers.

OBJECTIVE: We hypothesized that healthcare workers (HCWs) with high-risk exposures outside the healthcare system would have less asymptomatic coronavirus 2019 (COVID-19) disease and more symptoms than those without such exposures. DESIGN: A longitudinal point prevalence study was conducted during August 17-September 4, 2020 (period 1) and during December 2-23, 2020 (period 2). SETTING: Community based teaching health system. PARTICIPANTS: All HCWs were invited to participate. Among HCWs who acquired COVID-19, logistic regression models were used to evaluate the adjusted odds of asymptomatic disease using high-risk exposure outside the healthcare system as the explanatory variable. The number of symptoms between exposure groups was evaluated with the Wilcoxon rank-sum test. The risk of seropositivity among all HCS by work exposure was evaluated during both periods. INTERVENTIONS: Survey and serological testing. RESULT: Seroprevalence increased from 1.9% (95% confidence interval [CI], 1.2%-2.6%) to 13.7% (95% CI, 11.9%-15.5%) during the study. Only during period 2 did HCWs with the highest work exposure (versus low exposure) have an increased risk of seropositivity (risk difference [RD], 7%; 95% CI, 1%-13%). Participants who had a high-risk exposure outside of work (compared to those without) had a decreased probability of asymptomatic disease (odds ratio [OR], 0.38; 95% CI, 0.16-0.86) and demonstrated more symptoms (median 3 [IQR, 2-6] vs 1 [IQR, 0-4]; P = .001). CONCLUSIONS: Healthcare-acquired COVID-19 increases the probability of asymptomatic or mild COVID-19 disease compared to community-acquired disease. This finding suggests that infection prevention strategies (including masks and eye protection) may be mitigating inoculum and supports the variolation theory in COVID-19.

Effects of Salmonella enterica ser. Enteritidis and Heidelberg on host CD4+CD25+ regulatory T cell suppressive immune responses in chickens.

Poultry infected with Salmonella mount an immune response initially, however the immune responses eventually disappear leading the bird to be a carrier of Salmonella. The hypothesis of this study is that Salmonella infection induces T regulatory cell numbers and cytokine production and suppress host T cells locally in the gut to escape the host immune responses. An experiment was conducted to comparatively analyze the effect of S. enterica ser. Enteritidis (S. Enteritidis) and S. enterica ser. Heidelberg (S. Heidelberg) infection on CD4+CD25+ T regulatory cell properties in chickens. A total of 144 broiler chicks were randomly distributed into three experimental groups of non-infected control, S. Enteritidis infected and S. Heidelberg infected groups. Chickens were orally inoculated with PBS (control) or 5x106 CFU/mL of either S. Enteritidis or S. Heidelberg at 3 d of age. Each group was replicated in six pens with eight chickens per pen. Chickens infected with S. Enteritidis had 6.2, 5.4, and 3.8 log10 CFU/g, and chickens infected with S. Heidelberg had 7.1, 4.8, and 4.1 log10 CFU/g Salmonella in the cecal contents at 4, 11, and 32 dpi, respectively. Both S. Enteritidis and S. Heidelberg were recovered from the liver and spleen 4 dpi. At 4, 11, and 32 dpi, chickens infected with S. Enteritidis and S. Heidelberg had increased CD4+CD25+ cell numbers as well as IL-10 mRNA transcription of CD4+CD25+ cells compared to that in the control group. CD4+CD25+ cells from S. Enteritidis- and S. Heidelberg-infected chickens and restimulated with 1 µg antigen in vitro, had higher (P < 0.05) IL-10 mRNA transcription than the CD4+CD25+ cells from the non-infected controls Though at 4dpi, chickens infected with S. Enteritidis and S. Heidelberg had a significant (P < 0.05) increase in CD4+CD25- IL-2, IL-1ß, and IFNγ mRNA transcription, the CD4+CD25- IL-2, IL-1ß, and IFNγ mRNA transcription, were comparable to that in the control group at 11 and 32dpi identifying that the host inflammatory response against Salmonella disappears at 11 dpi. It can be concluded that S. Enteritidis and S. Heidelberg infection at 3 d of age induces a persistent infection through inducing CD4+CD25+ cells and altering the IL-10 mRNA transcription of CD4+CD25+ cell numbers and cytokine production in chickens between 3 to 32 dpi allowing chickens to become asymptomatic carriers of Salmonella after 18 dpi.

In-Network Data Aggregation for Ad Hoc Clustered Cognitive Radio Wireless Sensor Network.

In cognitive radio wireless sensor networks (CRSN), the nodes act as secondary users. Therefore, they can access a channel whenever its primary user (PU) is absent. Thus, the nodes are assumed to be equipped with a spectrum sensing (SS) module to monitor the PU activity. In this manuscript, we focus on a clustered CRSN, where the cluster head (CH) performs SS, gathers the data, and sends it toward a central base station by adopting an ad hoc topology with in-network data aggregation (IDA) capability. In such networks, when the number of clusters increases, the consumed energy by the data transmission decreases, while the total consumed energy of SS increases, since more CHs need to perform SS before transmitting. The effect of IDA on CRSN performance is investigated in this manuscript. To select the best number of clusters, a study is derived aiming to extend the network lifespan, taking the SS requirements, the IDA effect, and the energy consumed by both SS and transmission into consideration. Furthermore, the collision rate between primary and secondary transmissions and the network latency are theoretically derived. Numerical results corroborate the efficiency of IDA to extend the network lifespan and minimize both the collision rate and the network latency.

Characterizing the immune response of chickens to Campylobacter jejuni (Strain A74C).

Campylobacter is one of the major foodborne pathogens causing bacterial gastroenteritis worldwide. The immune response of broiler chickens to C. jejuni is under-researched. This study aimed to characterize the immune response of chickens to Campylobacter jejuni colonization. Birds were challenged orally with 0.5 mL of 2.4 x 108 CFU/mL of Campylobacter jejuni or with 0.5 mL of 0.85% saline. Campylobacter jejuni persisted in the ceca of challenged birds with cecal colonization reaching 4.9 log10 CFU/g on 21 dpi. Campylobacter was disseminated to the spleen and liver on 7 dpi and was cleared on 21 dpi from both internal organs. Challenged birds had a significant increase in anti-Campylobacter serum IgY (14&21 dpi) and bile IgA (14 dpi). At 3 dpi, there was a significant suppression in T-lymphocytes derived from the cecal tonsils of birds in the challenge treatment when compared to the control treatment after 72 h of ex vivo stimulation with Con A or C. jejuni. The T-cell suppression on 3 dpi was accompanied by a significant decrease in LITAF, K60, CLAU-2, IL-1ß, iNOS, and IL-6 mRNA levels in the ceca and an increase in nitric oxide production from adherent splenocytes of challenged birds. In addition, on 3 dpi, there was a significant increase in CD4+ and CD8+ T lymphocytes in the challenge treatment. On 14 dpi, both pro and anti-inflammatory cytokines were upregulated in the spleen, and a significant increase in CD8+ T lymphocytes in Campylobacter-challenged birds' ceca was observed. The persistence of C. jejuni in the ceca of challenged birds on 21 dpi was accompanied by an increase in IL-10 and LITAF mRNA levels, an increase in MNC proliferation when stimulated ex-vivo with the diluted C. jejuni, an increase in serum specific IgY antibodies, an increase in both CD4+ and CD8+ cells, and a decrease in CD4+:CD8+ cell ratio. The balanced Th1 and Th2 immune responses against C. jejuni might explain the ceca's bacterial colonization and the absence of pathology in Campylobacter-challenged birds. Future studies on T lymphocyte subpopulations should elucidate a pivotal role in the persistence of Campylobacter in the ceca.

Multispacer sequence typing of Coxiella burnetii from milk and hard tick samples from ruminant farms in Lebanon.

his study was carried out to detect and characterize Coxiella burnetii in ruminant milk samples and in different tick species from seropositive farms in four Lebanese regions. Milk and tick samples were screened for C. burnetii presence by quantitative real-time PCR (qPCR) targeting IS1111 region followed by multispacer sequence typing (MST). The overall positive percentages of 9.6% (27/282) and 95.45% (84/88) for C. burnetii were recorded in ruminant milk and tick samples, respectively. In detail, the C. burnetii DNA was recorded in 52/54 (96.3%) of Rhipicephalus annulatus, 20/21 (95.24%) of Rhipicephalus turanicus, 6/6 (100%) of Hyalomma anatolicum, 5/6 (83.3%) of Rhipicephalus sanguineus and 1/1 of Rhipicephalus bursa. After genotyping of some IS1111-positive samples (17/111), different MST genotypes were identified. Out of 15 positive ticks, 10 were infected with MST2 genotype, 4 were infected with MST7 genotype and 1 was infected with MST57. Moreover, genotypes MST20 and MST58 were found in one cow and one goat milk samples, respectively. The present study confirmed the high genetic diversity of C. burnetii in Lebanon.

In vitro characterization and analysis of probiotic species in the chicken intestine by real-time polymerase chain reaction.

Two experiments, 1 in vitro and 1 in vivo study, were conducted to analyze probiotic species characteristics and survival in the intestine of broiler birds. The in vitro study characterized the effect of bile salt supplementation and pH on the proliferation of Lactobacillus reuteri, Pediococcus acidilactici, Bifidobacterium animalis, and Enterococcus faecium. L. reuteri and P. acidilactici growth was maximal when the media was supplemented with 1.0% bile salt, whereas B. animalis and E. faecium growth was maximal when the media was supplemented with 0.5% bile salt. Altering the pH between 2.5 and 5.8 did not significantly (P > 0.05) alter the proliferation of L. reuteri and B. animalis. Decreasing the pH from 5.8 to 2.0 decreased P. acidilactici growth, whereas it increased the E. faecium proliferation. The in vivo study quantified the concentration of L. reuteri, P. acidilactici, B. animalis, E. faecium, and L. salivarius in different intestinal sections from birds supplemented with and without synbiotic containing the above 5 bacteria species. Birds were supplemented with and without synbiotic for 18 d, after which all birds were fed the same basal diet with no synbiotic. At 72 h of feeding, the basal diet with no synbiotics, when the probiotic species in the feed is expected not to confound the recovery of probiotic species from the intestine, intestinal contents were collected. L. reuteri, P. acidilactici, E. faecium, and L. salivarius were below detectable amount in the control group. L. reuteri concentration expressed as copy numbers/g and as percentage of total bacteria was highest in the jejunum and ileum, respectively. E. faecium concentration was highest in the ileum. The copy number of P. acidilactici increased at the duodenum and plateaued after duodenum. L. salivarius concentration was highest in the jejunum. It can be concluded that real-time PCR can be applied to quantify the concentrations of probiotic species in the intestine and probiotic species differ in their ability to colonize different sections of the intestine.

The First Serological Study of Q Fever in Humans in Lebanon.

OBJECTIVE: The aim of this study was to estimate, for the first time, the human seroprevalence of Q fever in Lebanon, by assessing the presence of antibodies against the causative agent, Coxiella burnetii. A total number of 421 serum samples (226 females and 196 males) were collected in February 2015 from hospitals and laboratories dispersed in five Lebanese provinces: Akkar, Bekaa, Mount Lebanon, Nabatieh, and South Lebanon. METHODS: Serial testing approach was used. Samples were first screened for IgG phase II antibodies against C. burnetii by Enzyme Linked Immunosorbent Assay (ELISA) Kit. Then, both positive and inconclusive sera were reexamined by immunofluorescence assay (IFA) test with the aims to confirm and specify the infection status (past or probably acute infection) by detecting IgG (I/II) and IgM (I/II) in human sera. RESULTS: Screening of 421 samples was estimated to be 38.70% (95% CI 34-43.3) positive samples, 5.90% (95% CI 3.7-8.2) suspect samples (as doubtful results), and 55.40% (95% CI 50.7-60.1) negative samples. Furthermore, all positive and suspect samples by ELISA test were retested by immunofluorescence assay test (IFAT), and the prevalence of positive sample was 37% and the infection case was recorded: 23.75% (95% CI 19.7-27.8) samples resulted from past infection, 1.9% (95% CI 0.6-3.2) probably acute infection characterized by several dominance clinical symptoms as: fever, cough, headache, difficulty breathing, and atypical pneumonia, and 0.23% (95% CI 0-0.7) inconclusive sample accompanied by different symptoms as bone metastasis and lung cancer. CONCLUSION: The study records the exposition of 37% of 421 patients to C. burnetii distributed in five Lebanese provinces with the highest seroprevalence in Bekaa and Akkar provinces and the lowest reported in Mount Lebanon. This difference may be due to the presence of high density of livestock production and of major agricultural areas in these two provinces.

Diversity and distribution of ticks from domestic ruminants in Lebanon.

Ticks (Acari: Ixodidae) are ectoparasites infesting livestock in every geographic area in the world and they are vectors of several viral, bacterial, and protozoan pathogens to animals and humans worldwide. A deep knowledge of the geographical distribution of these arthropods would have a key role in the control of tick-borne diseases. Few data are available about tick presence in domestic ruminants in Lebanon. The study aimed at providing an analysis of tick presence and distribution in Lebanon. Ticks were collected from cattle, sheep, and goats farms distributed in 6 Lebanese provinces between June and September 2014. A total of 272 adult hard ticks were randomly collected from domestic ruminants (cattle, sheep, and goats) located at 37 Lebanese farms, distributed among 30 villages. Ticks belonged to 4 Ixodidae genera: Rhipicephalus (72.4%), Haemaphysalis (11.4%), Dermacentor (8.1%), and Hyalomma (8.1%). They included the following species: Rhipicephalus annulatus (50.7%), Rhipicephalus turanicus (18.8%), Hyalomma anatolicum (8.1%), Haemaphylasis punctata (11.4%), Dermacentor marginatus (8.1%), Rhipicephalus sanguineus (2.5%), and Rhipicephalus bursa (0.4%). Rhipicephalus turanicus and H. anatolicum were found on cattle, sheep, and goats, R. annulatus on cattle and sheep, R. sanguineus, D. marginatus and Hea. punctata on sheep and goats, while R. bursa was collected only on sheep. Tick species involved in pathogen transmission were found and some of the identi ed species were recorded in Lebanon for the rst time.

Murine Embryonic Stem Cell Plasticity Is Regulated through Klf5 and Maintained by Metalloproteinase MMP1 and Hypoxia.

Mouse embryonic stem cells (mESCs) are expanded and maintained pluripotent in vitro in the presence of leukemia inhibitory factor (LIF), an IL6 cytokine family member which displays pleiotropic functions, depending on both cell maturity and cell type. LIF withdrawal leads to heterogeneous differentiation of mESCs with a proportion of the differentiated cells apoptosising. During LIF withdrawal, cells sequentially enter a reversible and irreversible phase of differentiation during which LIF addition induces different effects. However the regulators and effectors of LIF-mediated reprogramming are poorly understood. By employing a LIF-dependent 'plasticity' test, that we set up, we show that Klf5, but not JunB is a key LIF effector. Furthermore PI3K signaling, required for the maintenance of mESC pluripotency, has no effect on mESC plasticity while displaying a major role in committed cells by stimulating expression of the mesodermal marker Brachyury at the expense of endoderm and neuroectoderm lineage markers. We also show that the MMP1 metalloproteinase, which can replace LIF for maintenance of pluripotency, mimics LIF in the plasticity window, but less efficiently. Finally, we demonstrate that mESCs maintain plasticity and pluripotency potentials in vitro under hypoxic/physioxic growth conditions at 3% O2 despite lower levels of Pluri and Master gene expression in comparison to 20% O2.

The Oct4 protein: more than a magic stemness marker.

The Oct4 protein, encoded by the Pou5f1 gene was the very first master gene, discovered 25 years ago, to be absolutely required for the stemness properties of murine and primate embryonic stem cells. This transcription factor, which has also been shown to be essential for somatic cell reprogrammation, displays various functions depending upon its level of expression and has been quoted as a "rheostat" gene. Oct4 protein is in complexes with many different partners and its activity depends upon fine post-translational modifications. This review aims at revisiting some properties of this protein, which has not yet delivered all its potentialities.

The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.

BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4⁺CD25⁺ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4⁺CD25⁺ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.