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[EN]Brucella ovis is a non-zoonotic rough Brucella that causes genital lesions, abortions and increased perinatal mortality in sheep and is responsible for important economic losses worldwide. Research on virulence factors of B. ovis is necessary for deciphering the mechanisms that enable this facultative intracellular pathogen to establish persistent infections and for developing a species-specific vaccine, a need in areas where the cross-protecting ovine smooth B. melitensis Rev1 vaccine is banned. Although several B. ovis virulence factors have been identified, there is little information on its metabolic abilities and their role in virulence. Here, we report that deletion of pyruvate phosphate dikinase (PpdK, catalyzing the bidirectional conversion pyruvate ? phosphoenolpyruvate) in B. ovis PA (virulent and CO2-dependent) impaired growth in vitro. In cell infection experiments, although showing an initial survival higher than that of the parental strain, this ppdK mutant was unable to multiply. Moreover, when inoculated at high doses in mice, it displayed an initial spleen colonization higher than that of the parental strain followed by a marked comparative decrease, an unusual pattern of attenuation in mice. A homologous mutant was also obtained in a B. ovis PA CO2-independent construct previously proposed for developing B. ovis vaccines to solve the problem that CO2-dependence represents for large scale production. This CO2-independent ppdK mutant reproduced the growth defect in vitro and the multiplication/clearance pattern in mouse spleens, and is thus an interesting vaccine candidate for the immunoprophylaxis of B. ovis ovine brucellosis.

[EN]Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the main cause of human brucellosis. B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with an N-formyl-perosamine O-polysaccharide (O-PS) that is absent in the rough LPS of B. ovis. Their control and eradication require vaccination, but B. melitensis Rev 1, the only vaccine available, triggers anti-O-PS antibodies that interfere in the S-brucellae serodiagnosis. Since eradication and serological surveillance of the zoonotic species are priorities, Rev 1 is banned once B. melitensis is eradicated or where it never existed, hampering B. ovis control and eradication. To develop a B. ovis specific vaccine, we investigated three Brucella live vaccine candidates lacking N-formyl-perosamine O-PS: Bov::CA?wadB (CO2-independent B. ovis with truncated LPS core oligosaccharide); Rev1::wbdR?wbkC (carrying N-acetylated O-PS); and H38?wbkF (B. melitensis rough mutant with intact LPS core). After confirming their attenuation and protection against B. ovis in mice, were tested in rams for efficacy. H38?wbkF yielded similar protection to Rev 1 against B. ovis but Bov::CA?wadB and Rev1::wbdR?wbkC conferred no or poor protection, respectively. All H38?wbkF vaccinated rams developed a protracted antibody response in ELISA and immunoprecipitation B. ovis diagnostic tests. In contrast, all remained negative in Rose Bengal and complement fixation tests used routinely for B. melitensis diagnosis, though some became positive in S-LPS ELISA owing to LPS core epitope reactivity. Thus, H38?wbkF is an interesting candidate for the immunoprophylaxis of B. ovis in B. melitensis-free areas.

Abstract Background Individuals whose copies of the survival motor neuron 1 (SMN1) gene exist on the same chromosome are considered silent carriers for spinal muscular atrophy (SMA). Conventional screening for SMA only determines SMN1 copy number without any information regarding how those copies are arranged. A single nucleotide variant (SNV) rs143838139 is highly linked with the silent carrier genotype, so testing for this SNV can more accurately assess risk to a patient of having an affected child. Methods Using a custom-designed SNV-specific Taqman genotyping assay, we determined and validated a model for silent-carrier detection in the laboratory. Results An initial cohort of 21 pilot specimens demonstrated results that were 100% concordant with a reference laboratory method; this cohort was utilized to define the reportable range. An additional 177 specimens were utilized for a broader evaluation of clinical validity and reproducibility. Allelic-discrimination analysis demonstrated tight clustering of genotype groupings and excellent reproducibility, with a coefficient of variation for all genotypes ranging from 1% to 4%. Conclusion The custom-developed Taqman SNV genotyping assay we tested provides a rapid, accurate, and cost-effective method for routine SMA silent-carrier screening and considerably improves detection rates of residual risk for SMA carriers.

BackgroundTo examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer.MethodsData on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included.ResultsOf 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively.ConclusionsThese findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history.Trial registration numberUMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

As investigações sobre economia da partilha centram-se predominantemente em questões relacionadas com as partes envolvidas na troca (proprietário e usuário), nas plataformas eletrónicas da partilha, como Airbnb, e até mesmo o impacto urbano do Alojamento Locais em determinados destinos turísticos, porém o mercado secundário dos numerosos empresários que estão em torno do ecossistema da partilha, nomeadamente o Alojamento Local em particular, vem sido ignorado. Este estudo tem por objetivo investigar o ecossistema de atividades inerentes a exploração de Alojamento Local, identificar os principais serviços, como eles evoluíram e de que modo eles criam valor aos proprietários de AL no Porto, Portugal.Primeiramente, ao realizar um estudo exploratório, identificou-se as atividades que envolvem a gestão de um Alojamento Local categorizando-se os serviços na cadeia de valor de Porter. Em seguida, através de inquérito respondido por 211 proprietários de Alojamento Local, identificou-se quais os serviços mais subcontratados e como as empresas de gestão integral de propriedades criam valor para os proprietários. Posteriormente, foram entrevistadas empresas subcontratadas pelos proprietários a fim de se perceber seus modelos de negócio, como seus serviços evoluíram e como aportam valor aos proprietários.O que foi possível concluir com este estudo é que houve um intenso desenvolvimento da atividade de Alojamento Local e dos profissionais que prestam serviços de apoio aos proprietários durante o período de 2016 a 2018 na cidade do Porto. As empresas de gestão integral de propriedades são as mais subcontratadas pelos proprietários, o que mostra que estes buscam a conveniência de ter todos os serviços integrados em um único fornecedor. Em segundo lugar aparece a lavandaria, apesar do registo de carência de fornecedores que consigam manter padrão de qualidade. Seguem-se o contabilista, que tem sua relevância dada ao dinamismo do sistema fiscal português e o fotógrafo, o que estará associado ao investimento em marketing por parte dos proprietários, que percebem a importância de possuir fotografias de qualidade de suas propriedades que são utilizadas para os anúncios nas plataformas de arredamento, nas redes sociais e sites próprios.

The first complete genome sequence of Lactobacillus curvatus was determined by PacBio RS II. The single circular chromosome (1,848,756 bp, G+C content of 42.1%) of L. curvatus FBA2, isolated from fermented vegetables, contained low G+C regions (26.9% minimum) and 43 sets of >1,000-bp identical sequence pairs. No plasmids were detected.

.  Nagasaka K, Hojo S, Sakamoto K, Kakinoki S, Mori M, Takizawa K. Primary undifferentiated carcinoma arising from the retroperitoneum: a case report. Int J Gynecol Cancer 2005;15:1108–1111. A 35‐year‐old woman, gravida 1, para 1, underwent cesarean section in her 39th week of pregnancy. At the time of operation, multiple retroperitoneal tumors were found. Postoperative computed tomography and magnetic resonance imaging showed multiple solid tumors, each approximately 3–5 cm, in the right pelvic retroperitoneal space. Total resection of the tumors was performed without any macroscopic residual. A systematic workup for the primary tumor from which the retroperitoneal tumors may have metastasized failed to demonstrate any responsible tumor. We therefore assumed it to be a primary retroperitoneal tumor. The histopathologic features of the tumors were consistent with small‐cell carcinoma. Two months postoperatively, recurrent tumors in the right inguinal and common iliac regions were detected. Since chemotherapy with irinotecan hydrochloride or paclitaxel did not produce any beneficial effect, a second tumor reduction surgery was performed 8 months after the initial operation. Four months after the second operation, a third operation including total hysterectomy, bilateral salpingo‐oophorectomy, and tumor resection in the contralateral iliac region were done. Afterward, a new recurrent tumor appeared along the aorta up to the left supraclavicular node. The patient died 19 months after the first operation.