Notes

Non-linear and also non-additive organizations between the being pregnant metabolome as well as birthweight.
Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Approximately 80-90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR). A major drive of AChR antibody-positive MG pathology is represented by complement activation. The role of the complement cascade has been largely demonstrated in patients and in MG animal models. Complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChR. Given that the complement system works as an activation cascade, there are many potential targets that can be considered for therapeutic intervention. Preclinical studies have confirmed the efficacy of complement inhibition in ameliorating MG symptoms. Eculizumab, an antibody directed towards C5, has recently been approved for the treatment of AChR antibody-positive gMG. Other complement inhibitors, targeting C5 as well, are currently under phase III study. Complement inhibitors, however, may present prohibitive costs. Therefore, the identification of a subset of patients more or less prone to respond to such therapies would be beneficial. For such purpose, there is a critical need to identify possible biomarkers predictive of therapeutic response, a field not yet sufficiently explored in MG. This review aims to give an overview of the complement cascade involvement in MG, the evolution of complement-inhibiting therapies and possible biomarkers useful to tailor and monitor complement-directed therapies.Toxoplasma gondii is a widely prevalent protozoan parasite member of the phylum Apicomplexa. It causes disease in humans with clinical outcomes ranging from an asymptomatic manifestation to eye disease to reproductive failure and neurological symptoms. In farm animals, and particularly in sheep, toxoplasmosis costs the industry millions by profoundly affecting their reproductive potential. As do all the parasites in the phylum, T. gondii parasites go through sexual and asexual replication in the context of an heteroxenic life cycle involving members of the Felidae family and any warm-blooded vertebrate as definitive and intermediate hosts, respectively. During sexual replication, merozoites differentiate into female and male gametes; their combination gives rise to a zygotes which evolve into sporozoites that encyst and are shed in cat's feces as environmentally resistant oocysts. During zygote formation T. gondii parasites are diploid providing the parasite with a window of opportunity for genetic admixture making this a key step in the generation of genetic diversity. In addition, oocyst formation and shedding are central to dissemination and environmental contamination with infectious parasite forms. In this minireview we summarize the current state of the art on the process of gametogenesis. We discuss the unique structures of macro and microgametes, an insight acquired through classical techniques, as well as the more recently attained molecular understanding of the routes leading up to these life forms by in vitro and in vivo systems. We pose a number of unanswered questions and discuss these in the context of the latest findings on molecular cues mediating stage switching, and the implication for the field of newly available in vitro tools.In Leishmania, genetic exchange has been experimentally demonstrated to occur in the sand fly vector and in promastigote axenic cultures through a meiotic-like process. No evidence of genetic exchange in mammalian hosts have been reported so far, possibly due to the fact that the Leishmania species used in previous studies replicate within individual parasitophorous vacuoles. In the present work, we explored the possibility that residing in communal vacuoles may provide conditions favorable for genetic exchange for L. mexicana and L. amazonensis. Using promastigote lines of both species harboring integrated or episomal drug-resistance markers, we assessed whether genetic exchange can occur in axenic cultures, in infected macrophages as well as in infected mice. We obtained evidence of genetic exchange for L. amazonensis in both axenic promastigote cultures and infected macrophages. However, the resulting products of those putative genetic events were unstable as they did not sustain growth in subsequent sub-cultures, precluding further characterization.
This study aimed to evaluate the factors associated with death in patients with coronavirus disease 2019 by clarifying the clinical characteristics and immune responses.

The clinical characteristics and laboratory findings, including cytokine and lymphocyte subsets, were obtained from the electronic medical records of patients in Wuhan Tongji Hospital.

This study included 836 patients with confirmed COVID-19. JNKI-1 In total, 699 (83.6%) were cured and discharged, and 137 (16.4%) died. Our analysis revealed that age ≥ 65 years, male sex, malignancy, chronic obstructive pulmonary disease, dyspnea, dizziness, respiratory rate > 20 bpm, heart rate > 100 bpm, systolic blood pressure < 90 mmHg, neutrophils > 6.3×109/L, lymphopenia, thrombocytopenia, D-dimer ≥ 0.5 mg/L, lactate dehydrogenase > 250 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 μmol/L, albumin < 35 g/L, blood urea nitrogen > 9.5 mmol/L, estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardi cardiac troponin I, C-reactive protein ≥ 25 mg/L and procalcitonin ≥ 0.05 ng/ml were predictors of mortality in COVID-19 patients. Elevated cytokine levels and a continued increasing trend, including in IL-2R, IL-6, IL-8, IL-10 and TNFα, and a decrease in lymphocyte subsets, especially helper T cells, suppressor T cells and NK cells, were associated with a poor prognosis.
This study identified that an estimated glomerular filtration rate less then 90 ml/min/1.73, elevated cardiac troponin I, C-reactive protein ≥ 25 mg/L and procalcitonin ≥ 0.05 ng/ml were predictors of mortality in COVID-19 patients. Elevated cytokine levels and a continued increasing trend, including in IL-2R, IL-6, IL-8, IL-10 and TNFα, and a decrease in lymphocyte subsets, especially helper T cells, suppressor T cells and NK cells, were associated with a poor prognosis.
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