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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, usually chronic and has a progressive clinical course. Despite the availability of effective chemotherapy, TB is a leading killer of young adults worldwide and the global multi-drug resistant TB is reaching epidemic proportions. selleck compound Interrupt transmission through early detection and treatment of the patients is a main element of the drug-resistant TB control strategy. However, many drugable targets in pathogens are already inhibited by current antibiotics and there is not a biomarker that indicate normal or pathogenic biological processes, or pharmacological responses to therapeutic intervention. Studies directed at evaluate key elements of host response to infection may identify biomarkers with measurable characteristics that indicate pathogenic biological processes. Cell-derived microparticles (MPs) are membrane-coated vesicles that represent subcellular elements and have been identified increasingly in a broad range of diseases and emerging as potential novel biomarker to pathological processes. link2 In addition, MPs carry contents from their cells of origin as bioactive molecules as cytokines, enzymes, surface receptors, antigens and genetic information and may provide a means of communication between cells. Molecules-loaded MPs may interplay with the immune system and therefore can acts on inflammation, cell activation and migration. Therefore, MPs may be an important factor to immune process during Mtb infection, especially in pulmonary granulomas and influence the outcome of infection. Their characterization may facilitate an appropriate diagnosis, optimize pharmacological strategies and might be further explored as potential targets for future clinical interventions. The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread. Toll-like receptors (TLRs) are sensors of pathogen-associated molecules that trigger inflammatory signalling in innate immune cells including macrophages. All TLRs, with the exception of TLR3, promote intracellular signalling via recruitment of the myeloid differentiation factor 88 (MyD88) adaptor, while TLR3 signals via Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor-inducing interferon (IFN)-β (TRIF) adaptor to induce MyD88-independent signalling. Furthermore, TLR4 can activate both MyD88-dependent and -independent signalling (via TRIF). The study aim was to decipher the impact of the highly purified plant-derived (phyto) cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), when delivered in isolation and in combination (11), on MyD88-dependent and -independent signalling in macrophages. We employed the use of the viral dsRNA mimetic poly(IC) and endotoxin lipopolysaccharide (LPS), to induce viral TLR3 and bacterial TLR4 signalling in human Tamm-Horsfall protein-1 (THP-1)-derived macrophages, respectively. TLR3/TLR4 stimulation promoted the activation of interferon (IFN) regulatory factor 3 (IRF3) and TLR4 promoted the activation of nuclear factor (NF)-κB signalling, with downstream production of the type I IFN-β, the chemokines CXCL10 and CXCL8, and cytokine TNF-α. THC and CBD (both at 10 μM) attenuated TLR3/4-induced IRF3 activation and induction of CXCL10/IFN-β, while both phytocannabinoids failed to impact TLR4-induced IκB-α degradation and TNF-α/CXCL8 expression. The role of CB1, CB2 and PPARγ receptors in mediating the effect of THC and CBD on MyD88-independent signalling was investigated. TLRs are attractive therapeutic targets given their role in inflammation and initiation of adaptive immunity, and data herein indicate that both CBD and THC preferentially modulate TLR3 and TLR4 signalling via MyD88-independent mechanisms in macrophages. This offers mechanistic insight into the role of phytocannabinoids in modulating cellular inflammation. OBJECTIVE The risk of progression of multiple sclerosis (MS) related to the association of prognostic factors present at disease onset has rarely been explored. We aimed to construct a clinical risk score for MS long-term progression that could be easily applied in clinical practice. PATIENTS AND METHODS Among 432 patients with MS, 288 patients were selected as a derivation sample for identification of the knowledge prognostic factors more associated with long-term progression. One point was given to each risk factor identified as statistically significant by the adjusted model, and the sum of the points gave the overall risk score. Subsequently the score was applied to the remaining 144 patients to confirm if those with higher scores had reached MS secondary progression. RESULTS The prognostic factors identified as independently associated with long-term progression were no specific MS treatment before EDSS 3, age of onset older than 30 years, pyramidal and cerebellar impairment as the first manifestation of disease, time interval between the first and second relapses less than 2 years, and African ancestry. There was no significant difference between expected and observed number of patients in progression (44 vs. 31, p = 0.966), indicating that the score was able to predict the progression in the validation sample. There was no significant difference between patients with low risk (≤ 2 points) (p = 0.98) and high risk (≥ 3 points) (p = 0.48) in the derivation versus validation samples. In the derivation sample, the patients with three or more points had a 2.8-fold increased risk of progression [hazard ratio (HR) 2.8; 95 % confidence interval (CI) 1.2-6.3; p = 0.014). CONCLUSION The score proposed was capable of predicting long-term MS progression. We conducted an updated systematic review on the safety and efficacy of amantadine in cognitive recovery after traumatic brain injury (TBI), in order to determine if the current literature justifies its use in this clinical condition. A comprehensive search strategy was applied to three databases (PubMed, Scopus, and Cochrane). Only randomized clinical trials (RCTs) that compared the effect of amantadine and placebo in adults within 3 months of TBI were included in the review. Study characteristics, outcomes, and methodological quality were synthesized. This systematic review was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A quantitative synthesis (meta-analysis) was not feasible due to the large heterogeneity of studies identified. Three parallel RCTs and one cross-over RCT, with a total of 325 patients were included. All of the studies evaluated only severe TBI in adults. Amantadine was found to be well tolerated across the studies. Two RCTs reported improvement in the intermediate-term cognitive recovery (four to six weeks after end of treatment), using DRS (in both studies) and MMSE, GOS, and FIM-Cog (in one study). The effect of amantadine on the short-term (seven days to discharge) and long-term (six months from the injury) cognitive outcome was found not superior to placebo in two RCTs. The rate of severe adverse events was found to be consistently very low across the studies (the incidence of seizures, elevation in liver enzymes and cardiac death was 0.7 %, 1.9 %, and 0.3 %, respectively). In conclusion, amantadine seems to be well tolerated and might hasten the rate of cognitive recovery in the intermediate-term outcome. However, the long-term effect of amantadine in cognitive recovery is not well defined and further large randomized clinical trials in refined subgroups of patients are needed to better define its application. OBJECTIVE The aim of this study was to estimate the prevalence of low back pain (LBP) in patients with Parkinson's disease (PD) and its impact on functional capacity and quality of life. METHODS Patients with idiopathic PD answered a questionnaire and were submitted to a clinical and functional assessment. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr Scale, Beck Depression Inventory (BDI), McGill Pain Questionnaire (McGill), Roland Morris Disability Questionnaire (RMDQ), 39-item Parkinson's Disease Questionnaire (PDQ-39) were used. In addition, the ability to contract transversus abdominis (TrA) was assessed. RESULTS One hundred and fifteen patients answered the questionnaire, and 95 (82.6 %) reported painful symptoms. Of these, 67 (58.3 %) had chronic LBP, and approximately 40 % patients reported its onset before diagnosis of PD. Higher scores in pain intensity, depressive symptoms and UPDRS II and III, more advanced stages of PD, and absence of TrA contraction determined poor functional limitation induced by LBP. However, pain intensity (McGill), severity of PD symptoms (UPDRS III) and absence of TrA contraction were identified as predictive factors for functional limitation and explained 66.1 % of the variance in the RMDQ. Pain intensity and LBP-related disability caused negative impact on the quality of life. CONCLUSION LBP is common in patients with PD and it causes disability and poor quality of life. Pain intensity, UPDRS III and absence of TrA contraction were the most significant predictive factors for disability assessed by the RMDQ. V.BACKGROUND Environmental chemicals like phthalates, phenols and parabens may impact children's immune development and contribute to risk of atopic diseases and asthma. OBJECTIVE To evaluate the associations between prenatal and childhood phthalate exposure and child atopic diseases at the age of 9 years. METHODS The current analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child cohort (REPRO_PL). Phthalate metabolite levels were assessed in the urine samples collected from mothers during the 3 rd trimester of pregnancy and from children at age of 2 and 9 years. link3 For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical chart of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. RESULTS Higher urine concentration of 5oxo-MEHP increased the risk of food allergy in children at 9 years of age (O R =1.75, 95% CI1.