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Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. immune evasion | viral pathogenesis | cytokine receptor | poxvirus | inflammation

A study was conducted to characterize the function of phospholipase C (PLC) during the organization of the substrate in bilayers supporting mixtures of two, three or four components. Phosphorus contents were measured in the aqueous phase to determine enzyme activity. Results indicated that lipids stimulate the enzyme even during the existence of lamellar phases. Findings also showed that sphingomyelin inhibits PLC.

Objective. Pyloric atresia is a rare malformation, with an incidence of 1:100,000 live newborns. Male to female ratio is 1/1. Typically, it is an isolated malformation, with a good prognosis, but 20-40% of cases present epidermolysis bullosa, and to a lesser extent, multiple intestinal atresias. We present the case of a pre-term newborn prenatally diagnosed with polyhydramnios, duodenal atresia with "double bubble" sign, and suspected Down's syndrome, who eventually had pyloric atresia. [ABSTRACT FROM AUTHOR]

Preparations of purified full-length fusion (F) protein of human respiratory syncytial virus (HRSV) expressed in recombinant vaccinia-F infected cells, or of an anchorless mutant ([F.sub.TM-]) lacking the C-terminal 50 amino acids secreted from vaccinia-[F.sub.TM-]-infected cells contain a minor polypeptide that is an intermediate product of proteolytic processing of the F protein precursor FO. N-terminal sequencing of the intermediate demonstrated that it is generated by cleavage at a furin-motif, residues 106-109 of the F sequence. By contrast, the F1 N terminus derives from cleavage at residue 137 of FO which is also C-terminal to a furin recognition site at residues 131-136. Site-directed mutagenesis indicates that processing of FO protein involves independent cleavage at both sites. Both cleavages are required for the F protein to be active in membrane fusion as judged by syncytia formation, and they allow changes in F structure from cone- to lollipop-shaped spikes and the formation of rosettes by anchorless F.

Abstract: The cervical cancer represents a problem of public health and is considered the second reason of death by cancer in women. There have been described factors associated, related to the conduct, habits and infectious agents, such as Human Immunodeficiency Virus, herpes virus, Chlamydia trachomatis and Human Papilloma Virus (HPV). In order to establish risk factors and detect preinvasive cervical lesions, 101 samples of women from three indigenous ethnic groups of Zulia State were selected; to which a clinical-epidemiological survey was carried out to study the predisposing factors, in addition to the cytological study. Of the total of patients studied 33.66% were negative to the cytological study, while 66.34% had some type of alteration, observing that the Yukpa the most affected, 21 (20.79%) presented Cervical intraepithelial neoplasia and related infectious agents were found in 56.51% of the women. Coelocytic cells suggestive of HPV were found in 26.21% of all patients. When we analyzed the risk factors, we found that, the onset of sexual intercourse before age 15 as well as alcohol consumption were the most relevant. According to the findings, it is important the timely diagnosis in these communities, which are disassociated, and without access to health centers, whether due to living conditions or cultural implications. Resumen: El cáncer de cuello uterino (CaCu) representa un problema de salud pública y es considerado la segunda causa de muerte por cáncer en mujeres. Se han descrito factores de riesgo, los cuales están relacionados con hábitos, conductas y agentes infecciosos tales como el Virus de Inmunodeficiencia humana, herpes virus, Chlamydia trachomatis y Virus del Papiloma Humano (VPH). Con el fin de establecer los factores de riesgo y detectar lesiones preinvasivas de cérvix, se seleccionaron 101 mujeres de tres etnias indígenas, a las cuales se les realizó una encuesta clínico-epidemiológica, además del estudio citológico. Del total de pacientes estudiadas un 66,34% presentaron algún tipo de alteración, siendo las Yukpa las más afectadas, así mismo 21 (20,79%) presentaron neoplasia intraepitelial cervical y se encontraron agentes infecciosos en un 56,51% de las mujeres. En un 26,21% de las pacientes se encontraron células coilocíticas sugestivas de VPH. Al analizar los factores de riesgo se encontró que el inicio de relaciones sexuales antes de los 15 años, y el consumo de alcohol fueron los más relevantes. Es de importancia el diagnóstico oportuno en estas comunidades que se encuentran desasistidas y sin acceso a centros de salud, ya sea por condiciones de vida o por implicaciones culturales.

Presents a study which examined the origin of the lag period which was observed when phosphatidylcholine was bombarded by phospholipase C in bilayers of lipid compositions. Hydrolyzation of phospholipids by phospholipase C; What does not directly influence phospholipase C activity; Method used for the study; Results of the study.

Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice., Competing Interests: Declaration of interests WB has received consultancy or advisory board honoraria and speaker's bureau from Alexion, Novartis, Agios, Pfizer, Sanofi, and Sobi. BF has received consultancy or advisory board honoraria and speaker's bureau from Agios, Alexion, Apellis, Janssen, Novartis, Roche, Samsung, Sanofi, and Sobi. HF has received research support from Sanofi and Novartis. AG has received consultancy and research funds from Agios, Bristol Myers Squibb, Novo Nordisk, Saniona, Sanofi, Pharmacosmos, Novartis, AbbVie, and Vertex Pharmaceuticals. TJG-L has received research support from Sobi, Novartis, Amgen, Grifols; speakers bureau from Sobi, Novartis, Amgen, Grifols, argenx, Sanofi, Momenta, and Alpine; and fees for participation in data safety monitoring for Novartis and Alpine. IM has received consultancy honoraria from Alexion, Janssen, Novartis, Apellis, and Sanofi. MaM has received consultancy or speaker's bureau from Alexion, argenx, Sanofi, Novartis, and Sobi. MoM has received consultancy from Gilead, Novartis, AbbVie, and Pfizer. M-EM has received research support, consultancy and speaker's bureau from Amgen, Novartis, Novo Nordisk, Sanofi, Grifols, Sobi, Takeda, and CSL Bering. MN has received speaker fees from Sobi, Novo Nordisk, Amegn, Novartis, Kedrion, Bayer, Takeda, CSL Behring, and Sanofi, and consultancy honoraria from Bayer and CSL Behring. AP has received consultancy or speaker's bureau from Sanofi, Alexion, Novartis, Sobi, Pfizer, Gilead, and Morphosys. SR has received consultancy honoraria from Sanofi, Novartis, and Alexion. NV has received speaker's bureau from Sanofi, Amgen, and Grifols. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Evans syndrome (ES) is a rare condition, defined as the presence of 2 autoimmune cytopenias, most frequently autoimmune hemolytic anemia and immune thrombocytopenia (ITP) and rarely autoimmune neutropenia. ES can be classified as primary or secondary to various conditions, including lymphoproliferative disorders, other systemic autoimmune diseases, and primary immunodeficiencies, particularly in children. In adult ES, little is known about clinical features, disease associations, and outcomes. In this retrospective international study, we analyzed 116 adult patients followed at 13 European tertiary centers, focusing on treatment requirements, occurrence of complications, and death. ES was secondary to or associated with underlying conditions in 24 cases (21%), mainly other autoimmune diseases and hematologic neoplasms. Bleeding occurred in 42% of patients, mainly low grade and at ITP onset. Almost all patients received first-line treatment (steroids with or without intravenous immunoglobulin), and 23% needed early additional therapy for primary refractoriness. Additional therapy lines included rituximab, splenectomy, immunosuppressants, thrombopoietin receptor agonists, and others, with response rates >80%. However, a remarkable number of relapses occurred, requiring ≥3 therapy lines in 54% of cases. Infections and thrombotic complications occurred in 33% and 21% of patients, respectively, mainly grade ≥3, and correlated with the number of therapy lines. In addition to age, other factors negatively affecting survival were severe anemia at onset and occurrence of relapse, infection, and thrombosis. These data show that adult ES is often severe and marked by a relapsing clinical course and potentially fatal complications, pinpointing the need for high clinical awareness, prompt therapy, and anti-infectious/anti-thrombotic prophylaxis., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: The Latin American Network of Congenital Malformations: ReLAMC was established in 2017 to provide accurate congenital anomaly surveillance. This study used data from ReLAMC registries to quantify the prevalence of microcephaly from 2010 to 2017 (before, during and after the Zika virus epidemic)., Design: Nine ReLAMC congenital anomaly registries provided case-level data or aggregate data for any live births, still births or terminations of pregnancy with microcephaly. Births to pregnant women infected with Zika virus first occurred in Brazil in 2015, and in the remaining registry areas in 2016 with the exception of Chile that did not experience Zika virus. Therefore the prevalence of microcephaly for 2010-2014 and individual years 2015, 2016 and 2017 was estimated using multilevel random effect Poisson models. Clinical classification and characteristics of the cases were compared pre and post Zika for all centres providing individual case-level data., Results: The prevalence of microcephaly for all registries excluding Brazil was 2.3 per 10 000 (95% CI 2.0 to 2.6) for 2010-2014 rising to 5.4 (95% CI 4.8 to 6.0) in 2016 and 5.9 (95% CI 5.3 to 6.6) in 2017. Brazil had a prevalence of 0.6 per 10 000 (95% CI 0.5 to 0.6) in 2010-2014, rising to 5.8 (95% CI 5.6 to 6.1) in 2015, 8.0 (95% CI 7.6 to 8.3) in 2016 and then falling in 2017. Only 29 out of 687 cases of microcephaly were reported as congenital Zika syndrome in countries excluding Brazil., Conclusions: The prevalence of microcephaly was influenced both by Zika causing congenital Zika syndrome and by increased reporting awareness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pyloric atresia is a rare malformation, with an incidence of 1:100,000 live newborns. Male to female ratio is 1/1. Typically, it is an isolated malformation, with a good prognosis, but 20-40% of cases present epidermolysis bullosa, and to a lesser extent, multiple intestinal atresias. We present the case of a pre-term newborn prenatally diagnosed with polyhydramnios, duodenal atresia with "double bubble" sign, and suspected Down's syndrome, who eventually had pyloric atresia.