High Potential For Dissemination Research Articles

Peculiarities of online communication of trade union organizations with a youth audience

In a rapidly changing system of labor relations, trade union organizations increasingly recognize the importance of involving a young generation to maintain the stability of their functioning and effectiveness. At the same time, this social group is one of the most unprepared in terms of socio-legal and economic understanding of the essence of professional activity. Hence, it is obvious that both sides need each other. However, traditional means of mass information and mobilization no longer resonate with the digital media generation. Social networks come to the fore, specifically the Chinese platform TikTok. It has a high potential for dissemination of information and popularization of trade union organizations. The main purpose of this research paper is to explore the agenda for the relevant subject matter in this application. The main method is content analysis. Search requests were made using the following keywords: trade union (English language), związek zawodowy (Polish language) and profspilka (Ukrainian language). This way let us to expand the meaning and strengthen the weight of the results. Among other things, thematic content, content producers and means for its formation are determined. In conclusion, trade union organizations have already noticed the potential of the platform for communication with young people. Nonetheless, they have just begun to introduce this audience to their activities.

Correlations between the degree of infection by wild strain of Toxoplasma gondii in vitro and porcine hematological parameters

The apicomplexa Toxoplasma gondii is capable of actively proliferating in numerous types of nucleated cells, and therefore has a high potential for dissemination and resistance. Thus, the present work aimed to correlate the inoculum concentrations and amount of post-infection parasites with porcine hematological parameters (including biochemistry) through in vitro culture. Porcine blood was incubated with different concentrations of parasites (1.2 × 107, 6/3/1.5 × 106 cells/mL), then the concentrations of red blood cells (RBC) and their morphology, total and differential leukocytes, and free peptides were evaluated. In addition, eight different blood samples analyzed before inoculation, where subsequent multivariate analysis was applied to correlate different variables with trophozoite concentration. The results showed no significant variation (p < 0.05) in the relative levels of free peptides, or the relative percentage of RBC at all the parasite concentrations tested. However, the normalized percentages of leukocytes and neutrophils showed a significant reduction, while those of lymphocytes, eosinophils and monocytes showed the opposite behavior. Semi-automatic processing of images exhibited significant microcytosis and hypochromia. The multivariate analysis revealed a positive correlation between the amount number of protozoa (AP) and the variables: “Red cells” and “Neutrophils”, an indifference between the AP and the content of free peptides, and the concentration of monocytes in the samples; and a negative correlation for AP and the percentages of lymphocytes and eosinophils. Our results suggest that specific changes in hematological parameters may be associated with different degrees of parasitemia, demanding a thorough diagnostic process and adequate treatment.

A Customized Novel Blocking ELISA for Detection of Bat-Origin Swine Acute Diarrhea Syndrome Coronavirus Infection.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered emerging alphacoronavirus. SADS-CoV shares over 90% genome sequence identity with bat alphacoronavirus HKU2. SADS-CoV was associated with severe diarrhea and high mortality rates in piglets. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. Here, monoclonal antibody (MAb) 6E8 against SADS-CoV N protein accurately recognized SADS-CoV infection. Then, MAb 6E8 was utilized as a blocking antibody to develop blocking ELISA (bELISA). We customized the rN coating antigen with concentration 0.25 μg/mL. According to receiver operator characteristic curve analysis, the cutoff value of the bELISA was determined as 38.19% when the max Youden index was 0.955, and specificity was 100%, and sensitivity was 95.5%. Specificity testing showed that there was no cross-reactivity with other serum positive swine enteric coronaviruses, such as porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), porcine rotavirus (PoRV), and porcine sapelovirus (PSV). In conclusion, we customized a novel and high-quality blocking ELISA for detection of SADS-CoV infection, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection. IMPORTANCE SADS-CoV was reported to be of high potential for dissemination among various of host species. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. We customed a novel and high-quality bELISA assay for detection of SADS-CoV N protein antibodies, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection.

Electrochemical magneto-immunoassay for detection of zika virus antibody in human serum

Zika virus (ZIKV) is a flavivirus transmitted by infected Aedes genus mosquitoes. An infected person may be asymptomatic or present symptoms such as fever, arthralgia, and in pregnancy it may lead to neurological disorders in the fetus, such as microcephaly. Based on the high dissemination potential of ZIVK and its similar antigen composition to other arboviruses, new approaches for selective virus detection are urgently needed. This work reports the development of an electrochemical immunoassay for detection of anti-ZIKV antibodies, using magnetic beads functionalized with recombinant protein derived from the non-structural protein 1 (ΔNS1-ZIKV) and anti-IgG antibodies labeled with horseradish peroxidase (HRP) enzyme. The magneto-immunoassay uses disposable microfluidic devices for detection of anti-ZIKV in serum samples. A linear response was obtained for a wide concentration range from 0.01 to 9.80 × 105 pg mL−1 (r2 = 0.982), with a limit of detection of 0.48 pg mL−1. The proposed immunoassay proved to be highly efficient for the detection of anti-ZIKV antibodies in serum, offering promising perspectives for the development of fast, simple, and affordable point-of-care diagnosis devices for ZIKV.

Characterization of a Clostridioides difficile ST-293 isolate from a recurrent infection in Argentina

Clostridioides difficile is an opportunistic spore-forming pathogen responsible for antibiotic-associated diarrhea in humans. C. difficile produces two main toxins: TcdA and TcdB as well as a third toxin named binary toxin (CDT) that is also involved in virulence. The present study aimed at characterizing the C. difficile isolate ALCD3 involved in a relapse episode of nosocomial infection. Molecular characterization showed that isolate ALCD3 belongs to toxinotype 0/v and the MLST analysis demonstrated allelic profile adk:91, atpA:1, dxr:2, glyA: 1, recA:27, sodA: 1 and tpi:1 which corresponds to ST293 (MLST clade: 1). During growth, isolate ALCD3 showed an early increase in the sporulation ratio as well as maximal values of heat resistant forms after 2 days of incubation. Both sporulation kinetics and production of heat resistant forms were faster for isolate ALCD3 than for the reference strain VPI 10463. Germination in the presence of the natural germinant taurocholate was faster for isolate ALCD3 than for strain VPI 10463, which indicates that isolate ALCD3 starts cortex hydrolysis earlier than strain VPI 10463. Furthermore, the co-germinant glycine, induces rapid release of dipicolinic acid (DPA) in isolate ALCD3. These findings indicate that isolate ALCD3 is particularly efficient in both sporulation and germination. The present work represents the first report of the circulation of C. difficile ST293 in Argentina. The ability of isolate ALCD3 to produce toxins and its high sporulation/germination capacity are key features compatible with a microorganism with high dissemination potential and the possibility of inducing recurrent infections.

Multidrug-Resistant Biofilms (MDR): Main Mechanisms of Tolerance and Resistance in the Food Supply Chain.

Biofilms are mono- or multispecies microbial communities enclosed in an extracellular matrix (EPS). They have high potential for dissemination and are difficult to remove. In addition, biofilms formed by multidrug-resistant strains (MDRs) are even more aggravated if we consider antimicrobial resistance (AMR) as an important public health issue. Quorum sensing (QS) and horizontal gene transfer (HGT) are mechanisms that significantly contribute to the recalcitrance (resistance and tolerance) of biofilms, making them more robust and resistant to conventional sanitation methods. These mechanisms coordinate different strategies involved in AMR, such as activation of a quiescent state of the cells, moderate increase in the expression of the efflux pump, decrease in the membrane potential, antimicrobial inactivation, and modification of the antimicrobial target and the architecture of the EPS matrix itself. There are few studies investigating the impact of the use of inhibitors on the mechanisms of recalcitrance and its impact on the microbiome. Therefore, more studies to elucidate the effect and applications of these methods in the food production chain and the possible combination with antimicrobials to establish new strategies to control MDR biofilms are needed.

Association of the TGFβ gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy

In the complex tumor microenvironment, TGFβ is a pleiotropic cytokine involved in regulating cellular processes such as cancer cell proliferation, apoptosis and metastasis. TGFβ defines three subtypes (TGFβ1, TGFβ2, and TGFβ3), of which TGFβ is highly expressed in many cancers, especially those showing high dissemination potential. In addition, increased expression of TGFβ in multiple cancers is usually positively correlated with epithelial mesenchymal transition (EMT) and coordinated with the expression of genes driving EMT-related genes. TGFβ signaling in the tumor microenvironment inhibits the antitumor function of multiple immune cell populations, including T cells and natural killer cells, and the resulting immunosuppression severely limits the efficacy of immune checkpoint inhibitors and other immunotherapeutic approaches. As a major pathway to enhance the efficacy of cancer immunotherapy effects, the role of TGFβ signaling inhibitors have been evaluated in many clinical trials. However, the potential functions and mechanisms of TGFβ1, TGFβ2 and TGFβ3 in gastric cancer progression and tumor immunology are unclear. In this study, we comprehensively analyzed TGFβ1, TGFβ2 and TGFβ3 and gastric cancer microenvironmental features, including immune cell infiltration, EMT, hypoxia, mutation, immunotherapy and drug treatment, based on HMUCH sequencing data (GSE184336) and public databases. We also validated the protein expression levels of TGFβ in gastric cancer tissues as well as the role of TGFβ factor in cytology experiments. This report reveals the important role of the TGFβ gene family in gastric cancer and provides possible relationships and potential mechanisms of TGFβ in gastric cancer.

581-P: Implementing the 3Ms eHealth Intervention in Clinical Settings: Exploring Caregivers’ and Health Care Providers’ Impressions

Adolescence is a high-risk period during which youth with T1D often experience declines in illness management and increases in HbA1c. Black youth with T1D have higher HbA1cs and are more likely to engage in suboptimal management compared to White youth, elevating their risk. Parental monitoring, i.e., direct supervision of adolescents' daily diabetes care, is associated with youth diabetes management. eHealth interventions may be an effective strategy to increase parental monitoring with high dissemination potential. The present study explored caregivers’ and health care providers’ (HCP) impressions of The 3Ms, an eHealth intervention to improve parental monitoring of Black adolescents’ daily diabetes management. Semi-structured interviews were completed with caregivers (N=21) who completed The 3Ms and pediatric diabetes HCPs (N=7) . Data were analyzed using content analysis by two coders who resolved all coding discrepancies to consensus. Caregivers rated the helpfulness of The 3Ms 8.6 out of (SD = 1.4) and indicated a high likelihood of recommending The 3Ms to others (M = 9.2/10, SD = 1.4) . Primary themes were that The 3Ms was a helpful reminder to caregivers of the importance of parental supervision of adolescents’ diabetes care, The 3Ms mnemonic provided clear, simple supervision strategies, and the intervention increased collaboration between adolescents and caregivers. HCPs feedback centered on facilitators (e.g. HCP and institutional buy-in) and barriers (e.g. disruption to clinic flow, and resource limitations including space, staff, and technological resources) to using The 3Ms in diabetes clinics. HCPs reported that ancillary psychosocial support in conjunction with routine clinical care could benefit patients and families in improving diabetes health. Next steps include testing the efficacy of The 3Ms for improving caregivers’ supervision behaviors and improving youth diabetes outcomes. Disclosure M.Reardon: None. L.Mckenzie: None. A.I.Carcone: None. J.Weissberg-benchell: None. M.A.Evans: None. D.A.Ellis: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK11075- A1)

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein.

The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19. This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a–c to synthesize spiro-oxindoles 3a–d, 4a–e, and 5a–e. All compounds were tested in vitro against the SARS-CoV-2. Four spiro[indoline-3,5′-pyrido[2,3-d:6,5-d’]dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations. The four compounds exhibited potent inhibitory activity ranging from 40.23 ± 0.09 to 44.90 ± 0.08 nM and 40.27 ± 0.17 to 44.83 ± 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 ± 0.02 and 45 ± 0.06 nM against RdRp and spike glycoprotein, respectively. The computational study involving the docking studies of the binding mode inside two proteins ((RdRp) (PDB: 6m71), and (SGp) (PDB: 6VXX)) and geometrical optimization used to generate some molecular parameters were performed for the most active hybrids.

Reduction of the resistome risk from cow slurry and manure microbiomes to soil and vegetable microbiomes.

In cow farms, the interaction between animal and environmental microbiomes creates hotspots for antibiotic resistance dissemination. A shotgun metagenomic approach was used to survey the resistome risk in five dairy cow farms. To this purpose, 10 environmental compartments were sampled: 3 of them linked to productive cows (fresh slurry, stored slurry, slurry-amended pasture soil); 6 of them to non-productive heifers and dry cows (faeces, fresh manure, aged manure, aged manure-amended orchard soil, vegetables-lettuces and grazed soil); and, finally, unamended control soil. The resistome risk was assessed using MetaCompare, a computational pipeline which scores the resistome risk according to possible links between antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and human pathogens. The resistome risk decreased from slurry and manure microbiomes to soil and vegetable microbiomes. In total (sum of all the compartments), 18,157 ARGs were detected: 24% related to ansamycins, 21% to multidrugs, 14% to aminoglycosides, 12% to tetracyclines, 9% to β-lactams, and 9% to macrolide-lincosamide-streptogramin B. All but two of the MGE-associated ARGs were only found in the animal dejections (not in soil or vegetable samples). Several ARGs with potential as resistome risk markers (based on their presence in hubs of co-occurrence networks and high dissemination potential) were identified. As a precautionary principle, improved management of livestock dejections is necessary to minimize the risk of antibiotic resistance.

Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial

SummaryBackgroundAlthough many smokers use electronic cigarettes (e-cigarettes) to quit smoking, most continue to smoke while vaping. This dual use might delay cessation and increase toxicant exposure. We aimed to test the efficacy of a self-help intervention designed to help dual users to quit smoking.MethodsIn this three-arm randomised controlled trial we recruited individuals in the USA using Facebook and multimedia advertisements. Included participants were 18 years or older, smoked at least weekly in the preceding year, and vaped at least weekly in the preceding month. We used computer generated randomisation with balanced-permuted blocks (block size 10, with 2–4-4 ratio) to allocate participants to assessment only (ASSESS group), generic smoking cessation self-help booklets (GENERIC group), or booklets targeting dual users (eTARGET group). Individuals in the generic or targeted intervention groups received monthly cessation materials for 18 months, with assessments every 3 months for 24 months. The main outcome was self-reported 7-day point-prevalence smoking abstinence at each assessment point. All randomly allocated participants were included in primary analyses using generalised estimating equations for each of 20 datasets created by multiple imputation. Analysis of the χ2s produced an F test. The trial is registered with ClinicalTrials.gov, NCT02416011, and is now closed.FindingsBetween July 12, 2016, and June 30, 2017, we randomly assigned 2896 dual users (575 to assessment, 1154 to generic intervention, and 1167 to targeted self-help). 7-day point-prevalence smoking abstinence increased from 14% at 3 months to 42% at 24 months (F7,541·7=67·1, p<0·0001) in the overall sample. Targeted self-help resulted in higher smoking abstinence than did assessment alone throughout the treatment period (F1,973·8=10·20, p=0·0014 [α=0·017]). The generic intervention group had abstinence rates between those of the assessment and targeted groups, but did not significantly differ from either when adjusted for multiple comparisons (GENERIC vs eTARGET F1,1102·5=1·79, p=0·18 [α=0·05]; GENERIC vs ASSESS F1,676·7=4·29, p=0·039 [α=0·025]). Differences between study groups attenuated after the interventions ended.InterpretationA targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes.

Reducing intergenerational obesity and diabetes risk.

To address the intergenerational transmission of obesity and diabetes, strategies promoting the health of women of reproductive age appear to be urgently needed. In this narrative review, we summarise what has been learned from many prenatal clinical trials, discuss the emerging evidence from preconception clinical trials and highlight persistent gaps and critical future directions. Most trials tested prenatal interventions that resulted in a limited gestational weight gain of ~1kg and reduced gestational diabetes by 20-30%. These interventions also reduced macrosomia by 20-40% but had little-to-no impact on other offspring outcomes at birth or beyond. Far fewer trials tested preconception interventions, with almost all designed to improve conception or live-birth rates in overweight or obese women with infertility rather than reduce intergenerational risks in diverse populations. Preconception trials have successfully reduced weight by 3-9kg and improved markers of glucose homeostasis and insulin resistance by the end of the intervention but whether effects were sustained to conception is unclear. Very few studies have reported offspring outcomes at birth and beyond, with no evidence thus far of beneficial effects on offspring obesity or diabetes risks. Further efforts to develop effective and scalable strategies to reduce risk of obesity and diabetes before conception should be prioritised, especially for diverse and under-resourced populations at disparately high risk of obesity and diabetes. Future clinical trials should include interventions with high potential for dissemination, diverse populations, thorough maternal phenotyping from enrolment through to conception and pregnancy, and rigorous assessment of offspring obesity and diabetes risks from birth onwards, including into the third generation.

Aggressive behavior and recurrent spinal hydatid cyst

Hydatid cyst disease is caused by the parasite Echinococcus granulosus. Hydatidosis affecting the spine constitutes only 1% of cases. In 90% of the spinal cases, the disease is confined to the bone and the epidural space. Here we report a 25-year-old female patient, followed since the age of 3 for hepatic, renal and peritoneal hydatidosis, undergoing medical treatment (Albendazole). Operated 15 years ago (dorsal laminectomy) for spinal cord compression in consequence of the extension of the disease to the spinal cord at D12-L1 level. The course was marked by the progressive worsening of gait disorders with spinal deformity. The current examination shows a steppage gait and para paresis, without sensitive disorders. The osteotendinous reflexes are abolished in the 2 lower limbs. We also noted the presence of a significant thoracolumbar kyphoscoliosis. A spinal MRI demonstrated a recurrence of hydatidosis centered on the vertebral body of D11 which is practically destroyed with right and left para-vertebral extensions at D10, D11, D12 and epiduritis in D11 (A, B, C, D). Spinal CT confirms the almost complete lysis of the D11 vertebral body (Image E). Albendazole (400 mg p.o.) is administered twice daily. A Spondylectomy D11, curettage of the lesion and aspiration of necrotic tissue with spinal stabilization were proposed. Her situation remained unchanged after 4 months of follow-up. Although the hydatid cyst is characterized as benign pathology, in consequence of its local growing pattern, it can be classified in the malign group because of its high potential for dissemination, which can result in high incidence of recurrences.

Comparative genomics with a multidrug-resistant Klebsiella pneumoniae isolate reveals the panorama of unexplored diversity in Northeast Brazil.

The emergence of community acquired infections increases the public health concern on K. pneumoniae and closely related bacteria among which antimicrobial resistance spreads. We report a multidrug-resistant K. pneumoniae isolate, B31, of a patient infected in the community and admitted to an intensive care unit in Northeast Brazil. Antimicrobial susceptibility and genome information were thoroughly investigated to characterize B31 in front of 172 sequenced strains of different countries. Assigned to the Sequence Type 15, which is globally spread, B31 presented extended spectrum beta-lactamase, tigecycline and ciprofloxacin resistance. Genome sequencing revealed most resistance genes being carried by plasmids with high dissemination potential. The absence of main virulence factors, like yersiniabactin and colibactin, apparently suggests a mild pathogenic strain which, on the contrary, persisted and caused severe infection in a previously healthy patient. The present study contributes to unveil the unclear genomic scenario of virulent and multidrug-resistant K. pneumoniae in Brazil.

PROPOSTA DE INQUÉRITOS ADMINISTRATIVO E CLÍNICO PARA TOMADA DE DECISÃO NO ATENDIMENTO ODONTOLÓGICO EM TEMPOS DE PANDEMIA DE COVID-19

Profissionais da Odontologia estão constantemente expostos a vários microrganismos, incluindo o novo Coronavírus (SARS-CoV-2), que apresenta alto potencial de disseminação. Considerando que durante o atendimento odontológico são gerados aerossóis com a disseminação de gotículas de saliva (potencialmente contaminada pelo vírus), a contaminação dos profissionais e pacientes poderia ser aumentada mesmo tomando-se os cuidados de biossegurança necessários. Embora o risco de contaminação durante um atendimento odontológico ainda não tenha sido estimado, a padronização de condutas, previamente e durante o atendimento odontológico, é atitude necessária para minimizar a transmissão do SARS-CoV-2 entre profissionais e pacientes. O objetivo do presente trabalho é propor um modelo de inquérito administrativo e clínico, com fundamento clínico, ético e legal, para a tomada de decisão sobre atender (ou não) um paciente com necessidades odontológicas em tempos de pandemia de COVID-19. A identificação de pacientes sintomáticos utilizando instrumentos sistematizados para coleta de informações pode minimizar o risco de contaminação por profissionais ou pacientes e, além disso, estes instrumentos podem subsidiar o profissional contra alegações infundadas, por parte dos pacientes, em casos de não atendimento.

Oropouche Virus Infects, Persists and Induces IFN Response in Human Peripheral Blood Mononuclear Cells as Identified by RNA PrimeFlow™ and qRT-PCR Assays.

Oropouche orthobunyavirus (OROV) is an emerging arbovirus with a high potential of dissemination in America. Little is known about the role of peripheral blood mononuclear cells (PBMC) response during OROV infection in humans. Thus, to evaluate human leukocytes susceptibility, permissiveness and immune response during OROV infection, we applied RNA hybridization, qRT-PCR and cell-based assays to quantify viral antigens, genome, antigenome and gene expression in different cells. First, we observed OROV replication in human leukocytes lineages as THP-1 monocytes, Jeko-1 B cells and Jurkat T cells. Interestingly, cell viability and viral particle detection are maintained in these cells, even after successive passages. PBMCs from healthy donors were susceptible but the infection was not productive, since neither antigenome nor infectious particle was found in the supernatant of infected PBMCs. In fact, only viral antigens and small quantities of OROV genome were detected at 24 hpi in lymphocytes, monocytes and CD11c+ cells. Finally, activation of the Interferon (IFN) response was essential to restrict OROV replication in human PBMCs. Increased expression of type I/III IFNs, ISGs and inflammatory cytokines was detected in the first 24 hpi and viral replication was re-established after blocking IFNAR or treating cells with glucocorticoid. Thus, in short, our results show OROV is able to infect and remain in low titers in human T cells, monocytes, DCs and B cells as a consequence of an effective IFN response after infection, indicating the possibility of leukocytes serving as a trojan horse in specific microenvironments during immunosuppression.

Treatment options for COVID-19: The reality and challenges.

An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2–5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.

Interleukin‑33 expression in ovarian cancer and its possible suppression of peritoneal carcinomatosis.

Refractory peritoneal carcinomatosis is a common terminal feature of epithelial ovarian cancer(EOC). Previous reports have suggested that immunotherapy is a promising therapeutic strategy for EOC. Interleukin (IL)‑33 is a member of the IL‑1 superfamily of cytokines. The role of IL‑33 in tissue inflammation and promoting type2 immune responses has been established, and recently, there is accumulating evidence to suggest the involvement of IL‑33 in carcinogenesis. In this study, we focused on the association between the tumor expression of IL‑33 and ovarian peritoneal carcinomatosis. We used an immunosufficient murine model of peritoneal carcinomatosis and human EOC samples. The overexpression of IL‑33 in the ID8 mouse EOC cell line tumors significantly prolonged the survival of immunocompetent mice in the peritoneal carcinomatosis setting, but not in the subcutaneous model. In addition, the silencing of IL‑33 in ID8‑T6 cells (subclone with high dissemination potential) significantly shortened the survival of the tumor‑bearing mice. This was likely due to the intratumoral accumulation of CD8+ and CD4+ Tcells, and a decrease in CD11b+Gr1+ cells. Furthermore, IL‑33 induced the intraperitoneal microenvironment favoring tumor elimination through the inhibition of differentiation into CD11b+Gr1+ cells. On the whole, the findings of this study suggest IL‑33 to be a cytokine that reflects antitumor peritoneal conditions. Further investigation of the antitumorigenic role of IL‑33 may aid in the development of more effective therapeutic approaches for the treatment of EOC with peritoneal carcinomatosis.

Characterisation, antimicrobial resistance and diversity of atypical EPEC and STEC isolated from cow's milk, cheese and dairy cattle farm environments

This study was carried out to determine the occurrence and characteristics of enteropathogenic Escherichia coli (EPEC) and Shiga toxin-producing E. coli (STEC) strains in cow's milk, cheese and dairy cattle farm environments, and to estimate distribution of antimicrobial resistance. A collection of 18 atypical EPEC -aEPEC, 14 STEC, and one E. albertii was obtained and characterized from 502 samples. Occurrence of aEPEC in cow's milk was high (>6%) whereas non-O157 STEC was isolated in ca. 2% of milk samples. Detection of these diarrheagenic E. coli was absent in more than 100 cheese samples obtained from raw milk. This is the first report identifying E. albertii (O69:HNM) in a dairy cattle farm. Nearly one-third of aEPEC strains showed antimicrobial resistance, mostly presenting a multidrug resistance pattern. One clonal complex (ST20 Cplx) containing aEPEC strains from milk and faecal samples was determined. Two STEC strains belonged to serotypes with importance in human disease (O91:H21 and O55:H8) and were isolated from air samples which suggests a high dissemination potential. Spanish bulk tank cow's milk can constitute an important source of aEPEC strains besides STEC, bearing multiple antimicrobial resistance and with high diversity of both serotypes and genetic features linked to potential human infection.

Dissemination of blaOXA-370 is mediated by IncX plasmids and the Tn6435 transposon.

In Enterobacteriaceae, the blaOXA-48-like genes have been identified on plasmids in different regions of the world. The OXA-370 is a plasmid-encoded OXA-48-like enzyme reported in two distinct regions of Brazil. Recently, we demonstrate that the blaOXA-370 gene is disseminated among several Enterobacteriaceae species and clones, indicating a high potential for dissemination. In this work, we described for the first time the complete nucleotide sequence of six plasmids harboring the blaOXA-370 gene. Complete DNA sequencing using the Illumina platform and annotation of the plasmids showed that they belonged to incompatibility groups IncX and had in average 70kbp. The blaOXA-370 gene is located in a composite transposon containing four genes encoding transposases, named Tn6435. In this study, highly similar plasmids were detected in different Enterobacteriaceae genera.