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The hydrate morphology in sandy methane hydrate (MH)-bearing sediment (MHBS) is commonly classified as pore-filling, cementation, grain-coating and load-bearing. This paper presents a numerical investigation into the mechanical behaviour of coexistence-type MHBS using the discrete-element method (DEM). The coexistence type is represented as a combination of pore-filling and cementation types. For MHBS with a given MH saturation (S MH), the relative content of pore-filling and cementation is characterised by the cement ratio λ (λ = 0 means pure pore-filling and λ = 1 means pure cementation). A series of drained triaxial compression tests is simulated, and micromechanical variables such as bond breakage are examined. The results show that (a) the strength and dilatancy of the coexistence-type MHBS are higher when the cement ratio is larger. The normalised strength and secant modulus increase linearly with the cement ratio. (b) When the cement ratio increases, the critical-state line on the mineral void ratio e cr–ln p′ projection shifts towards a higher position and the bond breakage ratio is larger. (c) The shear stress of the coexistence-type MHBS with cementation is affected by the MH generation process due to the MH bond breakages.

Під час розвитку маститу у корів формування біоплівки збудником захворювання є ефективним способом його збереження в мікрооточенні молочної залози. Біоплівкові інфекції важко піддаються лікуванню антимікробними засобами, порівняно з тим, що спостерігається при вирощуванні в планктонних умовах. Мета роботи – визначити та порівняти вплив антимікробних препаратів та бактеріофагу Phage SAvB14 при знищенні біоплівок сформованих S. aureus var. bovis. За результатами дослідження встановлено, що антибіотики згубно впливали на кількість бактерій у складі біоплівки, проте знищували її, в середньому, на 60%. 100% ефективність проявляв лише один антибіотик фторхінолонового ряду – енрофлоксацин - ймовірно, через його низьку молекулярну масу. При дослідженні впливу бактеріофагу Phage SAvB14 на життєздатність S. aureus var. bovis у складі біоплівки встановлено, що фаг впродовж 24 годин повністю руйнував сформовану біоплвку. Отже, отримані результати вказують на перспективність ефективного використання стафілококового бактеріофагу Phage SAvB14 для руйнування біоплівки, сформованої S. aureus var. bovis – при маститі корів.

Although we develop influenza immunity from an early age, it is insufficient to prevent future infection with antigenically novel strains. One proposed way to generate long-term protective immunity against a broad range of influenza virus strains is to boost responses to the conserved epitopes on the hemagglutinin, the major surface glycoprotein on the influenza virus. Influenza-specific humoral immunity comprises a large fraction of the overall immune memory in humans, and it has been long recognized that preexisting immunity to influenza shapes the response to subsequent influenza infections and vaccinations. However, the mechanisms by which preexisting immunity modulates the response to influenza vaccination are still not completely understood. Using a set of mathematical models, we explore several hypotheses that may contribute to diminished boosting of antibodies to conserved epitopes after repeated vaccinations.

Soda residue is a by-product of sodium carbonate manufacturing and has a highly adsorptive capacity for heavy metal ions. Thus, this research intended to utilise soda residue to remediate zinc (Zn)-contaminated soil by partial replacement of cement based on the stabilisation/solidification (S/S) method. Then, the effectiveness of S/S based on cement blended with soda residue was evaluated through an unconfined compressive strength (UCS) test, an electrical resistivity test and the toxicity characteristic leaching procedure (TCLP). Results show that UCS increases with the increase in total binder content and curing time, while it decreases with the increase in zinc ion (Zn2+) concentration in the soil. The leached zinc ion concentration determined through TCLP decreases with increasing curing time. Increasing the curing time, mass ratio of cement to soda residue and total binder content results in an increase in the electrical resistivity of the specimen, while a reverse trend occurs with the increase in zinc ion concentration. Based on the results of X-ray diffraction analysis and scanning electron microscopy, the formation of hydrated products such as calcium silicate hydrate, calcium aluminate hydrate and ettringite can be detected, as well calcium zincate hydrate (CaZn2(OH)6H2O), which is responsible for zinc ion immobilisation.

The aim of this paper is to describe and analyze the main features and trends of the private-wage Youth Labour Market (YLM) in Chile between 2010-2019. The study uses a quantitative method research design to examine, in the first place, salary trends and socio-demographic and occupational characteristics of the YLM; and second, to analyze the numerical flexibility in terms of contracts, working hours, and outsourcing. The results suggest that the wage process of young people has stopped in the private sector. Furthermore, young workers have higher levels of numerical flexibility, lower wages, and are inserted in unskilled service occupations, despite having higher credentials than adults. The latter could be explained by labour segmentation mechanisms and the role that the youth labour market plays in the neoliberal economic order., El presente artículo tiene por objetivo describir y analizar las principales características y tendencias del mercado laboral juvenil (MLJ) asalariado privado en Chile para el periodo 2010-2019. Mediante un diseño metodológico cuantitativo descriptivo se examinan, en primer lugar, las tendencias de asalarización y principales características sociodemográficas y ocupacionales para 2010-2019; y segundo, las transformaciones en la flexibilidad numérica en términos de contratos, jornadas y subcontratación laboral. La evidencia sugiere que la asalarización del MLJ se ha detenido en el sector privado, en tanto, las personas jóvenes registran salarios más bajos, se insertan en ocupaciones de servicio no calificados, pese a tener mayores credenciales, y registran una mayor flexibilidad que las personas adultas. Lo último podría estar explicado por mecanismos de segmentación laboral y el rol que el propio MLJ juega en el funcionamiento del orden económico neoliberal.

Plant extracts have been considered for the control the leaf-cutting ants. The objectives of this study were to evaluate the survival leaf-cutting worker ants after topical application of Ageratum conyzoides (mentrasto) and Manihot esculenta (cassava) extracts; and to evaluate the effect of Manihot esculenta hexane extract via ingestion on the survival of the workers of Atta sexdens Forel 1908 isolated or not from their colonies, in order to verify whether the symbiotic fungus Leucoagaricus gongylophorus confers protection to the workers against the extract. First, ten medium workers were removed from their colonies and received the application of 1 μL of extract on the pronotum. The cassava extract (125 µg.mL-1) was diluted in a solution of honey with water for the ingestion bioassay. Five repetitions (ten ants inside a transparent plastic container) were performed in each of the four colonies used in the experiment. The numbers of dead ants were recorded daily until the control also died. The solution of the hexane Manihot esculenta extract gave a significant result at the concentration of 100 µg.mL-1, with 100% of mortatily after 4 days. The ants maintained with the symbiont fungus that ingested the cassava hexanic extract showed a lower mortality rate (40% at the end of 25 days) than the workers who were kept isolated (90%). The symbiosis between the ants and the fungus means more than a food source for leaf-cutting ants because it reduces the toxic effect on the ants when the ants remain in contact with the fungus and is offered an unsafe vegetable.

The emergence and worldwide spread of Methicillin-resistant Staphylococcus aureus (MRSA) pose a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (Panthera tigris altaica) using an MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the Siphoviridae family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, anti-phagocytosis, and biofilm formation. Challenge of the lysogenic strain (SA14+) caused severe mortalities in both Galleria mellonella and mouse models. Mice challenged with SA14+ showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-γ and TNF-α) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of “bacteria-phage-interactions” in MRSA.

World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) d...

Background Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant cause of skin and soft tissue infections (SSTIs), which is a problem in prisons and jails. We conducted this study to understand MRSA molecular characteristics among inmates with SSTIs, and we chose MRSA isolates from a community hospital as a comparison. Methods A total of 219 MRSA isolates from three custodial facilities and 134 isolates from a community hospital in Taiwan were collected in the 2017 calendar year. MRSA isolates were investigated molecularly by staphylococcal chromosome cassette mec (SCCmec) type, mupirocin, and chlorhexidine genotypical resistance, and multi-locus sequence typing (ST). Results Of the 219 MRSA isolates from custodial facilities, SCCmec IV was the most prevalent type (65.3%), followed by type VT (32.4%) and type V (1.8%). Regarding sequence types, ST59 (36.4%), 8 (35.3%), and 45 (17.9%) were the leading three predominant types out of 184 selected MRSA isolates, and ST45 MRSA was more prevalent in custodial facilities (p = 0.019). The antimicrobial resistance rates varied for different MRSA strains, with ST45 MRSA having the lowest rates of resistance to most antimicrobials. Overall, 91.5% of isolates carried mupA gene and 25.8% were positive for qacA/B gene, this was independent of the MRSA sequence types. Conclusions ST59, ST8, and ST45 MRSA are the leading three MRSA strains causing SSTIs in Taiwan, 2017, but the molecular distribution varied distinctly between the custodial facilities and hospital settings. The genotypical mupirocin resistance rate is quite high in this study. The frequency of chlorhexidine resistance gene is relatively low, especially in MRSA isolates from custodial facilities.

Shigellosis appears to increase in certain at-risk populations in developed countries. Based on the nationwide surveillance, the annual incidence of shigellosis in Taiwan (1999-2019) was 0.38-5.77 cases per 100,000 people. Indigenous shigellosis has mostly affected men who have sex with men (MSM) and people living with HIV (PLWH) since 2015. In this retrospective study, compared with those diagnosed before 2015, indigenous cases diagnosed during 2015–2019 mostly occurred in male adults (96.0% vs 47.1%, P

Background Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. Methods Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline in vitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC = 4 mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. Results All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1 mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. Conclusion In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

Coronavirus disease 2019 is a pandemic disease, which commonly presents with fatigue, loss of smell, fever and ground-glass opacities on diagnostic imaging of the lungs. After the first few months of the pandemic, we noticed a tendency for audio-vestibular complaints on out-patient visits post-hospitalization for COVID-19. Objective. The aim of this study was to study the prevalence of audio-vestibular complaints in COVID-19. Materials and methods. This study included 57 patients with audio-vestibular complaints during and after hospitalization for COVID-19 at University Hospital Kaspela in Plovdiv, Bulgaria. The patients underwent both auditory and vestibular tests, as well as a computed tomography of the cranial brain. Results. The ratio of males to females was 1,35:1, with most belonging to the age group of 51 to 70 years (63,2%). All 57 patients had sudden hearing loss – unilateral in 36 (63,2%) and bilateral in 21 (36,8%), while 17 patients (29.8%) additionally had subjective tinnitus. Forty-eight patients (84,2%) had vestibular complaints – general dizziness in 46 (95,8%) and rotatory vertigo in two (4,2%). Two patients had spontaneous nystagmus (3,5%), 43 (75,4%) – saccades, and 25 (43,9%) – smooth pursuit and gaze disturbances. Romberg with closed eyes was positive in two patients (3,5%), and Fukuda lateralized to the healthy ear also in two patients (3,5%). Dix-Hallpike was positive in one patient (1,8%). The video head-impulse test was positive in two patients (3,5%). Vascular encephalopathy was found on computed tomography in 33 patients (57,9%). Conclusions. Coronavirus disease 2019 may be associated with vestibulocochlear nerve damage, and in most cases, it is an isolated injury to the auditory nerve. Complaints of dizziness are most likely due to vascular changes in the central nervous system.

The disease of obesity has quickly escalated from an epidemic to a worldwide pandemic in the last few decades, and viable treatment methods are being investigated with urgency. One such treatment method is increased induction of the thermogenesis pathway that is active in brown adipose tissue. This pathway is typically activated in mammals when they are exposed to cold temperatures for extended periods of time but can also be induced exogenously. Thermogenesis is a metabolically inefficient process that occurs in the mitochondria of a cell, meaning it uses substrate energy without generating ATP. The inefficiency of this process allows excess energy storage to be used and therefore serves as possible method of treatment. This review investigates the thermogenesis pathway and the ways it can be used to prevent and treat obesity.

Programmed cell death-1 (PD-1; CD279) is a cell surface receptor that is expressed in both innate and adaptive immune cells. The role of PD-1 in adaptive immune cells, specifically in CD8sup+/supT cells, has been thoroughly investigated but its significance in other immune cells is yet to be well established. This review will address the role of PD-1 based therapies in enhancing non-CD8sup+/supT cell immune responses within cancer. Specifically, the expression and function of PD-1 in non-CD8sup+/supimmune cell compartments such as CD4sup+/supT helper cell subsets, myeloid cells and innate lymphoid cells (ILCs) will be discussed. By understanding the immune cell specific function of PD-1 within tissue resident innate and adaptive immune cells, it will be possible to stratify patients for PD-1 based therapies for both immunogeneic and non-immunogeneic neoplastic disorders. With this knowledge from fundamental and translational studies, PD-1 based therapies can be utilized to enhance T cell independent immune responses in cancers.

Objective: Inosine monophosphate (IMP) is a key factor that imparts of meat flavor. Differences in the IMP content in the muscles were evaluated to improve chicken meat quality.Methods: For this study, the IMP content was detected by high performance liquid chromatography. The gene expression profiles of Jingyuan chickens with different feeding patterns and different sexes were analyzed by RNA-sequencing (RNA-seq).Results: Breast muscle IMP content in free-range chickens was extremely significantly higher than that of caged chickens (p

The gut-brain axis has paved our way in understanding varieties of disease. The gut microbiota especially the bacterial population plays critical roles in immune system development and function. Glioma comprises 80 percent of malignant brain cancer and glioblastoma (GBM) is the most malignant kind. GBM has a reputation for its suppressive immune environment and poor patient prognosis. Moreover, altered metabolites from gut microbiota affect both systemic immune and central nervous system (CNS) immunity. Here we will focus on the crosstalk between gut microbiota and GBM, and further explore how this communication contributes to glioma initiation and development. Finally, we highlight the latest insights on the metabolic regulation of immunity through gut microbiota, which provides a promising therapeutic strategy for GBM.

The goal of this work was to systematically characterize and detect class 1, 2, and 3 integrons with many antibiotic resistance A. baumannii strains collected from a clinical environment in Iraq's Al-Muthanna hospitals. In this investigation, 24 non-replicated clinical strains of A. baumannii were evaluated using Chrome agar as a selective medium and PCR of the rplB gene. The clonal relatedness of the isolates to class 1 integron was evaluated using a PCR technique. The prevalence of class 1 integron was detected by PCR in only 12 clones of A. baumannii followed by HinfI digestion analysis showing three identical bands at 160 bp, 1350 bp, and 870 bp. In addition, PCR sequencing confirmed the presence of gene cassette arrays consisting of aacA4-catB8-aadA1 (100%) in class 1 integron. The sequence analysis of the integron shows 97.87 identity with A. baumannii isolates from Australia (GenBank accession number CP054302) among A. baumannii isolates. The blast analysis of this class I integron showed that the presence of the intI1, aacA4-catB8-aadA1 genes can considerably boost the acquisition of MDR phenotypes in A. baumannii isolates. We concluded that antibiotics of many types are widely used. The presence of integrons in A. baumannii is concerning for public health. In the clinical setting, it appears that the class 1 integron can be used as a predictive biomarker for the presence of MDR phenotypes. In these bacteria, however, the integron does not possess carbapenemases genes.

To our knowledge, this study represents the first demonstration of Arthrographis kalrae biofilm formation in vitro by scanning electron microscopy and the distinct cytotoxic activity between planktonic and biofilm extracts on RAW 264.7 cell line. Higher activity was observed with biofilm. It could impact host immune response, that require furthers study.

Introduction Clostridioides difficile biofilms are believed to protect the pathogen from antibiotics, in addition to potentially contributing to recurrent infections. Methodology Biofilm production of 102 C. difficile isolates was determined using the crystal violet staining technique, and detachment assays were performed. The expression levels of cwp84 and slpA genes were evaluated by real-time PCR on selected isolates. Results More than 70% of isolates (75/102) were strong biofilm producers, and the highest detachment of biofilm was achieved with the proteinase K treatment (>90%). The overall mean expression of cwp84 was higher in RT027 than in RT001 (p = 0.003); among strong biofilm-producing strains, the slpA expression was lower in RT027 than in RT001 (p Conclusions Proteins seem to have an important role in the biofilm's initial adherence and maturation. slpA and cwp84 are differentially expressed by C. difficile ribotype and biofilm production level.

Aims The aim of the study was to determine the performance of Xpert MTB/RIF assay in diagnosing tuberculosis on thoracoscopic pleural biopsies in exudative pleural effusion. Methods Patients who underwent thoracoscopic pleural biopsy in the defined period were included in the study. Histopathology was done for all and Xpert MTB RIF assay and AFB culture of pleural biopsy specimen and pleural fluid were done as per the clinician's discretion. Results Total of 110 patients underwent pleural biopsy and tissue Xpert MTB/RIF and MTB culture were done in 29 patients. XpertMTB/RIF assay and MTB culture had a sensitivity of 59% and 35% respectively and specificity of specificity of 100. Conclusion The study described the ability of XPERT MTB/RIF in getting additional diagnostic information from thoracoscopic Pleural biopsy. Pleural biopsy Xpert MTB/RIF had sensitivity of 59% and specificity of 100% in diagnosing TPE. In addition to the diagnosis, Xpert MTB/RIF can also give valuable information about rifampicin resistance too. XPERT MTB/RIF assay also helped in getting diagnosis when histopathology alone was not able to confirm or rule out the diagnosis of TPE. Pleural fluid ADA of 38 IU/L had a sensitivity of 71% and a specificity of 86% for diagnosis of TPE in present study.

Context: Transrectal ultrasound-guided prostate biopsy (TRPB) has been a standard of care for diagnosing prostate cancer but is associated with a high incidence of infectious complications. Objective: To achieve an expert consensus on whether fosfomycin trometamol provides adequate prophylaxis in TRPB and discuss its role as prophylaxis in transperineal prostate biopsy (TPPB). Evidence acquisition: An international multidisciplinary group of experts convened remotely to discuss how to best use fosfomycin in various clinical settings and patient situations. Six statements related to prostate biopsy and the role of fosfomycin were developed, based on literature searches and relevant clinical experience. Evidence synthesis: Consensus was reached for all six statements. The group of experts was unanimous regarding fosfomycin as a preferred candidate for antimicrobial prophylaxis in TRPB. Fosfomycin potentially also meets the requirements for empiric prophylaxis in TPPB, although further clinical studies are needed to confirm or refute its utility in this setting. There is a risk of bias due to sponsorship by a pharmaceutical company. Conclusions: Antimicrobial prophylaxis is mandatory in TRPB, and fosfomycin trometamol is an appropriate candidate due to low rates of resistance, a good safety profile, sufficient prostate concentrations, and demonstrated efficacy in reducing the risk of infectious complications following TRPB. Patient summary: Patients undergoing transrectal ultrasound-guided prostate biopsy (TRPB) have a high risk of infectious complications, and antimicrobial prophylaxis is mandatory. However, increasing antimicrobial resistance, as well as safety concerns with fluoroquinolones, has restricted the number of antimicrobial options. Fosfomycin trometamol meets the requirements for a preferred antimicrobial in the prophylaxis of TRPB.

The stress–strain behaviour of concrete confined by fibre-reinforced polymer (FRP) is an important part of studying the seismic rehabilitation of concrete structures. Most previous studies have investigated the stress–strain behaviour of concrete prisms confined by polymer composites without preloading, but concrete columns are under various loading conditions before being retrofitted with polymer confinement. Therefore, in this study, FRP-confined concrete cylinders with different preloading ratios were prepared to examine the effect of preloading on the behaviour of retrofitted concrete columns. The results indicated that preloading affects important points of stress–strain curve. Preloading up to 75% of the unconfined concrete strength had a positive effect on the stress–strain behaviour, but 90% preloading reduced the strength of the FRP-confined concrete. A modification for the stress–strain models of preloaded FRP-confined concrete is thus suggested.

Intratumour heterogeneity (ITH) is pervasive across all cancers studied and may provide the evolving tumour multiple routes to escape immune surveillance. Immune checkpoint inhibitors (CPIs) are rapidly becoming standard of care for many cancers. Here, we discuss recent work investigating the influence of ITH on patient response to immune checkpoint inhibitor (CPI) therapy. At its simplest, ITH may confound the diagnostic accuracy of predictive biomarkers used to stratify patients for CPI therapy. Furthermore, ITH is fuelled by mechanisms of genetic instability that can both engage immune surveillance and drive immune evasion. A greater appreciation of the interplay between ITH and the immune system may hold the key to increasing the proportion of patients experiencing durable responses from CPI therapy.

The 2019 novel coronavirus disease (COVID-19) is the disease that has been identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the prophylactic treatment of SARS-CoV-2 is still under investigation. The effective delivery of eukaryotic expression plasmids to the immune system’s inductive cells constitutes an essential requirement for the generation of effective DNA vaccines. Here, we have explored the use of Salmonella typhimurium as vehicles to deliver expression plasmids orally. Attenuated Salmonella phoP harboring eukaryotic expression plasmids that encoded spike protein of SARS-CoV-2 was administered orally to Wistar rats. Rats were immunized orally with Salmonella that carried a eukaryotic expression plasmid once a week for three consecutive weeks. The efficiency of the vaccination procedure was due to the transfer of the expression plasmid from the bacterial carrier to the mammalian host. Evidence for such an event could be obtained in vivo and in vitro. Our results showed that all immunized animals generated humoral immunity against the SARS-CoV-2 spike protein, indicating that a Salmonella-based vaccine carrying the Spike gene can elicit SARS-CoV-2-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV-2 infection.

We report a case of vancomycin-induced thrombocytopenia (VIT) with rapid onset after re-exposure to vancomycin. A 58-year-old man with cellulitis was initiated on vancomycin. Approximately 1 hour into the vancomycin infusion, the patient developed an infusion-related reaction. Vancomycin infusion was stopped. A complete blood count obtained 4 hours after discontinuation of the vancomycin infusion revealed a platelet count of 31 ×10­9/L. Investigations ruled out likely causes of thrombocytopenia. VIT was diagnosed based on clinical symptoms and confirmed with drug-dependent platelet antibody testing. Without complications, platelet counts recovered within 7 days after discontinuation of vancomycin. No correlation between vancomycin level and VIT was observed.

[poster presented at iMarCo congress, abstract from the Molecular Ecology related article] All metazoans are in fact holobionts, resulting from the association of several organisms, and organismal adaptation is then due to the composite response of this association to the environment. Deciphering the mechanisms of symbiont acquisition in a holobiont is therefore essential to understanding the extent of its adaptive capacities. In cnidarians, some species acquire their photosynthetic symbionts directly from their parents (vertical transmission) but may also acquire symbionts from the environment (horizontal acquisition) at the adult stage. The Mediterranean snakelocks sea anemone, Anemonia viridis (Forskål, 1775), passes down symbionts from one generation to the next by vertical transmission, but the capacity for such horizontal acquisition is still unexplored. To unravel the flexibility of the association between the different host lineages identified in A.viridis and its Symbiodiniaceae, we genotyped both the animal hosts and their symbiont communities in members of host clones in five different locations in the North Western Mediterranean Sea. The composition of within-host–symbiont populations was more dependent on the geographical origin of the hosts than their membership to a given lineage or even to a given clone. Additionally, similarities in host–symbiont communities were greater among genets (i.e. among different clones) than among ramets (i.e. among members of the same given clonal genotype). Taken together, our results demonstrate that A.viridis may form associations with a range of symbiotic dinoflagellates and suggest a capacity for horizontal acquisition. A mixed-mode transmission strategy in A.viridis, as we posit here, may help explain the large phenotypic plasticity that characterizes this anemone.

Methicillin-resistant Staphylococcus aureus (MRSA), biofilms, and persisters are three major factors leading to recurrent and recalcitrant implant infections. Although antibiotics are still the primary treatment for chronic implant infections in clinical, only few drugs are effective in clearing persisters and formed biofilms. Here, felodipine, a dihydropyridine calcium channel blocker, was reported for the first time to have antibacterial effects against MRSA, biofilm, and persisters. Even after continuous exposure to sub-lethal concentrations of felodipine, bacteria are less likely to develop resistance. Besides, low doses of felodipine enhances the antibacterial activity of gentamicin by inhibiting the expression of protein associated with aminoglycoside resistance (aacA-aphD). Next, biofilm eradication test and persisters killing assay suggested felodipine has an excellent bactericidal effect against formed biofilms and persisters. Furthermore, the result of protein profiling, and quantitative metabonomics analysis indicated felodipine reduce MRSA virulence (agrABC), biofilm formation and TCA cycle. Then, molecular docking showed felodipine inhibit the growth of persisters by binding to the H pocket of ClpP protease, which could lead to substantial protein degradation. Furthermore, murine infection models suggested felodipine in combination with gentamicin alleviate bacterial burden and inflammatory response. In conclusion, low dose of felodipine might be a promising agent for biomaterial delivery to enhance aminoglycosides efficacy against implant infections caused by MRSA, biofilm, and persisters.

The type III secretion system (T3SS) is a key factor in the pathogenesis of Pseudomonas syringae pv. actinidiae biovar 3 (Psa3), the causal agent of a global kiwifruit bacterial canker pandemic. To monitor the T3SS expression levels in Psa3, we constructed a luciferase reporter plasmid-expressing HrpAPsa3-NLuc fusion protein. The expression of HrpA-NLuc was induced in hrp-inducing conditions whereas the level of luciferase activity correlated with the expression of hrp/hrc genes in Psa3 confirmed the reliability of the reporter construct. Based on the readout of the NLuc reporter construct, three small molecule compounds 4-methoxy-cinnamic acid, sulforaphane, and ferulic acid were determined as T3SS inhibitors in Psa3, whereas sodium acetate was determined to be a T3SS inducer. Moreover, the aqueous extract of fruit inhibited the accumulation of HrpA-NLuc in Psa3 in medium and in planta. Additionally, the T3SS inhibitors suppress Psa3 virulence, whereas the T3SS inducer promotes Psa3 virulence on kiwifruit. Thus, our findings may provide clues to why the fruit is not infected by Psa3, and the Psa3 T3SS inhibitors have potential as alternatives to current nonspecific antimicrobials for disease management.

Molecular interactions of indomethacin (IND) and amino acids (AA) were investigated in this work by employing the computational approaches. To this aim, the models of IND-AA were stabilized by performing density functional theory (DFT) calculations yielding the most favorable configurations regarding the energy values. Next, the approach of quantum theory of atoms in molecules (QTAIM) was used to recognize the roles of interactions and their significance in the bimolecular models. The results of interaction energies indicate that tryptophan (TRP) and phenylalanine (PHE) could be considered for participating in strong interactions with the IND substance. The results of QTAIM indicated that not only the electronegative atomic centers, but also homo-atomic centers could play significant roles in formations of IND-AA bimolecular models.

Facing the increasingly fierce competition in the current society, enterprises must take corresponding measures to deal with the dynamic environment. In order to improve their competitive advantages, they must pay more attention to the quality of their product, activate the organizational quality specific immune. This study takes organizational quality specific immune as the entry point to construct the organizational quality specific immune evaluation indicator system, and establishes three criteria layers of organizational quality monitoring and cognition, organizational quality defense, clearance and repair, and organizational quality memory and immune stabilization, there are a series of indicators under each criterion layer. Then this study constructs the organizational quality specific immune evaluation model based on optimal combination weight methods, and the optimal combination weighting model is introduced to conduct empirical study of evaluating organizational quality specific immune with 15 large-scale manufacturing enterprises in eastern regions. And the pros and cons of the organizational quality specific immune status of 15 large-scale manufacturing enterprises in eastern regions are finally obtained. The organizational quality specific immune evaluation indicators, organizational quality specific immune evaluation model based on optimal combination weighting methods and empirical analysis results of organizational quality specific immune evaluation based on optimal combination weighting methods and model will provide theoretical significance and practical enlightenment for enhancing organizational quality performance and organizational health.

Popliteal artery aneurysm (PAA) has been increasingly treated with endovascular intervention in recent years. However, whether transpedal access can be utilized to treat PAA has not been widely reported. We report a case of successful treatment of a PAA with a covered stent via retrograde transpedal approach in an 80-year male with prohibitive surgical risk who initially failed antegrade approach. This case demonstrates the feasibility of treating PAA via a retrograde transpedal access in selected patients.

Assessing the importance of intrinsic and extrinsic factors that shape the spatial distribution of genetic diversity of symbionts has been a topic of debate for decades. While host-mediated dispersal is an important driver of gene flow in many terrestrial metazoan symbionts, few studies have identified the drivers of symbiont genetic differentiation in the marine realm, where habitats are comparatively more homogeneous and long-distance dispersal is common. In the present study, we perform a meta-analysis of existing studies examining symbiont spatial genetic diversity to determine which symbiont- and host-related traits shape the patterns of genetic differentiation of metazoan symbionts, while also considering technical aspects of each study. Specifically, we wanted to assess the influence of biological traits and/ or technical aspects in (1) detecting genetic differentiation in marine symbionts, and (2) shaping the minimum spatial scale at which genetic differentiation was detected. By assessing genetic diversity of mtDNA markers, we found that the spatial scale at which studies are conducted was a crucial predictor of both detection of genetic structure and scale at which differentiation of marine symbionts was detected. Symbiont-based traits did not influence genetic structure, however, host-mediated dispersal was the only biological trait that shaped genetic structure of marine symbionts by influencing the spatial distribution at which differentiation was detected.

The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting. Herein, we have developed a microenvironment-activated poly(ethylene glycol) (PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries. The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands, thereby facilitating targeted codelivery of ciprofloxacin (CIP) and IR780 to the bacteria after accumulation within biofilms. The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment, triggering rapid drug release on demand around bacterial cells. The self-modulating nanoplatform under near-infrared (NIR) irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone. Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats. This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

Abstract: Interferon-simulated gene 15 (ISG15) belongs to the family of ubiquitin-like proteins. ISG15 acts as a cytokine and modifies proteins through ISGylation. This posttranslational modifica-tion has been associated with antiviral and immune response pathways. In addition, it is known that the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes proteases critical for viral replication. Consequently, these proteases are also central in the progression of coro-navirus disease 2019 (COVID-19). Interestingly, the protease SARS-CoV-2-PLpro removes ISG15 from ISGylated proteins such as IRF3 and MDA5, affecting immune and antiviral defense from the host. Here, the implications of ISG15, ISGylation, and generation of SARS-CoV-2-PLpro inhibitors in SARS-CoV-2 infection are discussed.

Introduction: The authors aimed to investigate the biofilm-forming features of panresistant Klebsiella pneumoniae (PRKp). Material & methods: The biofilm formations were shown under light microscope and laser scanning confocal microscopy. The optical densities of the wells were measured and classified according to biofilm-forming capacities. Results: The ratio of biofilm-forming K. pneumoniae was established to be 100%. All isolates were found to form high-level biofilms in classification compared with positive and negative controls. No significant difference was detected in the biofilm-forming capacities of K. pneumoniae strains isolated from different sample types. Conclusion: No previous study associated with PRKp isolates was identified in the literature search. There is a need for different approaches characterizing the biofilm-forming features of PRKp.

Background:The emergence and spread of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae is now a major challenge in treating urinary tract infections. This study was conducted to determine the Prevalence of ESBL genes inKlebsiella pneumoniaeand the influence of these genes on the antimicrobial susceptibility patterns of the isolates, obtained from community acquired urinary tract infection in Enugu state rural communities. Method:A total of 735 clean catch mid-stream urine samples were collected from February, 2021 to June, 2021. The urine samples were cultured andKlebsiella pneumoniaewere identified morphologically, biochemically, and then typed down, using PCR, Gel electrophoresis, and Sanger Sequencing by Genewiz. Antibiotic susceptibility testing was done by modified Kirby-Bauer disc diffusion method and interpretation was done following Clinical and Laboratory Standard Institute (CLSI) guidelines. ESBL screening was done by the phenotypic method, using the standard disk diffusion method, whereas the phenotypic confirmation of ESBL producers was done by the double-disk synergy method, and interpreted according to CLSI guidelines. Multiplex PCR was used to detect the genes for SHV and CTX-M while conventional linear PCR was done for TEM andblasGES type ESBL genes. Results:A total of 77 isolates were identified asKlebsiella pneumoniae, and the prevalence of positive ESBL in them were 10(12.9%). Of the 77 isolates that were tested for antibiogram, 29 isolates were multidrug-resistance (MDR). Out of the MDR isolates, 10 were ESBL positive, whereas 19 were not. Of this 29 MDR isolates, 6 were extensively-drug resistant (XDR). Of the 6 XDR isolates, 3 do not possess ESBL enzymes, whereas 3 of them do. Age range of 31-40 contributed the highest prevalence of ESBL genes (60%), whereas age range of 10-20, 21-30, and 51-70 did not produce any ESBL gene.blaTEM gene was the most prevalent ESBL resistant genes with a prevalence of 10 (100%), followed by SHV 9(90%), whereasblaGES gene andblaCTX-M have the least prevalence of 4 (40%) each. Conclusion:Higher prevalence of MDR, XDR, and ESBL-producingKlebsiella pneumoniaewere observed, thus the need for public health intervention for effective prevention and control of antimicrobial resistance, and proper treatment of UTIs.

AIM. Previous studies have provided insights into complex immune system changes caused by ischemic stroke (IS), while detailed reports are lacking especially in peripheral blood. Here, we sought to identify genetic biomarkers in immune system which significantly associated with the occurrence of IS and explore candidate drugs that can regulate the process. We also investigated whether gene expression alternation of immune genes contributed to differential distribution of immune cells in peripheral blood following IS. Method. 108 IS samples and 47 matched controls were obtained from the GEO database. Immune-related genes (IRGs) and their associated drugs were collected from the ImmPort and PharmGBK databases, respectively. Random forest (RF) regression and least absolute shrinkage and selection operator (LASSO) logistic regression were applied to identify immune-related genetic biomarkers (IRGBs) of IS, and accuracy was verified using neural network models. Finally, proportion changes of various immune cells in peripheral blood of IS patients were evaluated using CIBERSORT and xCell and correlation analyses were performed between IRGBs and differentially distributed immune cells. Results. A total of 537 genes were differentially expressed between IS and control samples. Four immune-related differential expressed genes identified by regression analysis presented strong predictive power ( AUC = 0.909 ) which we suggeseted them as immune-related genetic biomarkers (IRGBs). We also demonstrated six immune-related genes targeted by known drugs. In addition, post-IS immune system presented an increase in the proportion of innate immune cells and a decrease in adaptive immune cells in the peripheral circulation, and IRGBs showing significance were associated with this process.Conclusion. The study identified CARD11, ICAM2, VIM, and CD19 as immune-related genetic biomarkers of IS. Six immune-related DEGs targeted by known drugs were found and provide new candidate drug targets for modulating the post-IS immune system. The innate immune cells and adaptive immune cells are diversified in the post-IS immune system, and IRGBs might play important role during this process.

Background: Inversion of chromosome 9 (inv[9]) is known as one of the most common structural balanced chromosomal variations. Chromosome 9 is highly susceptible to structural rearrangements, specifically to pericentric inversions. Various investigators have posited that inv(9) with different breakpoints could be the cause of several abnormal conditions in individuals, whereas others have considered it a benign variant. To our knowledge, a consensus regarding the effects of this inversion has yet to emerge. Objective: This study aims to discuss the pathogenic/benign effects of inv(9) in all possible clinical conditions detected in the occurrence of this abnormality. Methods: Studies on inv(9) were collected via PubMed, MalaCards, Google Scholar, and NORD, along with the search terms of inv(9), pericentric inv(9), and chromosome 9 variants. Additionally, the incidence of inv(9) and the karyotype and clinical findings of individuals reported with this variant were investigated. Results: The collection of the studies reviewed shows that inv(9) is associated with various conditions such as congenital anomalies, growth retardation, infertility, recurrent pregnancy loss, and cancer. The clinical features associated with this variant in humans vary between growth stages. Further, there have been no shared clinical findings in a specific period. Conclusions: Although there is no conclusive evidence for the pathogenicity of this rearrangement, prenatal genetic counseling on inv(9) and further clinical and molecular studies would be helpful in chromosome 9-related problems.

Weidong Qian,1 Xinchen Li,1 Min Yang,1 Chanchan Liu,2 Yi Kong,3 Yongdong Li,4 Ting Wang,1 Qian Zhang5 1School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, People’s Republic of China; 2Xi’an Medical College, Xi’an, 710309, People’s Republic of China; 3Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, the General Hospital of the People’s Liberation Army, Beijing, 100048, People’s Republic of China; 4Ningbo Municipal Center for Disease Control and Prevention, Ningbo, 315010, People’s Republic of China; 5Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518004, People’s Republic of ChinaCorrespondence: Ting Wang; Qian Zhang, Tel +10 29-86168583, Email wangtingsp@sust.edu.cn; zhangqianbisheng@163.comPurpose: Several Escherichia coli pathotypes still constitute an important public health concern owing to its pathogenicity and antimicrobial resistance. Moreover, biofilm formation of E. coli can allow the strains to interfere with host and antimicrobial eradication, thus conferring additional resistance. The association between the formation of biofilm and antimicrobial resistance determinants has been extensively exploited; nevertheless, there is still no definite conclusion. The purpose of this study was to provide additional data to augment the present knowledge about the subject.Methods: Antibiotic resistance/susceptibility profiles of 81 isolates from pediatric individuals in China between 2011 and 2014 against 20 antibiotics were assessed using the VITEK 2 system. Biofilm-forming capacities were evaluated using the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy. Biofilm compositions inside the biofilm formed by representative strains were assessed using CLSM. The effects of antibiotics on biofilms generated by E. coli strains of different biofilm-forming ability were examined using CLSM in combination with gatifloxacin. The relationships between antibiotic resistance, biofilm formation, and biofilm-specific resistance in E. coli isolates were investigated.Results: The results showed that 23 isolates were classified as multidrug-resistant, and 57 isolates were classified as extensively drug-resistant (XDR). Among the 69 isolates with the ability to form biofilms, 46 isolates were stronger biofilm formers. Correlation analysis demonstrated that strain populations exhibiting more robust biofilm formation likely contained larger proportions of XDR isolates.Conclusion: Together, our study implies that there was an association between biofilm-formation and resistance to several antibiotics for XDR-E. coli isolates, and would provide novel insights regarding the prevention and treatment against E. coli-related infections.Keywords: Escherichia coli, biofilm, antibiotic resistance, biofilm-specific resistance

Alternative solutions are eminently needed to combat the escalating number of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Bacteriocins produced by lactic acid bacteria are promising candidates for next-generation antibiotics. Studies have found that these stable and nontoxic ribosomally synthesized antimicrobial peptides exhibit significant potency against other bacteria, including antibiotic-resistant strains. Here the authors review previous studies on bacteriocins that have been effectively employed to manage MRSA infections. The authors' review focuses on the beneficial traits of bacteriocins for further application as templates for the design of novel drugs. Treatments that combine bacteriocins with other antimicrobials to combat pervasive MRSA infections are also highlighted. In short, future studies should focus on the pharmacodynamics and pharmacokinetics of bacteriocins–antimicrobials to understand their interactions, as this aspect would likely determine their efficacy in MRSA inhibition.

Integrons are genetic platforms used for expressing open reading frames (ORFs) arranged in gene cassettes. Excision and integration of gene cassettes are controlled by their associated integron integrase (IntI). Using IntegronFinder software, we analyzed all complete halophilic genomes available in the HaloDom database, along with selected partial halophilic genomes. We identified 18 new complete bacterial integrons and 46 clusters of attC sites lacking a neighboring integron integrase (CALINs). Different classes of insertion sequences (ISs) were also identified within and near integrons and CALINs, with an abundance of IS1182 elements and different ISs that can presumably mobilize adjacent genomic structures. Different promoters of intI genes (PintI) showed nearby binding sites for arginine repressor (ArgR), raising the possibility that IntI expression and recombination activity are regulated by these proteins. Our findings revealed the existence of new integrons in halophilic bacteria with possible adaptive roles.

Objectives Despite excessive resistance of Helicobacter pylori to clarithromycin among Iranian population, unfortunately, clarithromycin-based therapy is still prescribed in Iran. Recent studies have shown high rates of H. pylori eradication in patients treated with levofloxacin. The main purpose of this study was to compare the effect of levofloxacin with clarithromycin on the eradication of H. pylori infection in Iranian population. Methods A comprehensive meta-analysis was done for the relevant cohort studies and clinical trials to compare the therapeutic effects of levofloxacin with clarithromycin in Iranian population. We pooled the data using odds ratio corresponding to 95% confidence intervals to find the clinical efficacy of levofloxacin versus clarithromycin to treat H. pylori infection. The heterogeneity and publication bias were also measured for the included studies. Results A total of 13 studies were included in the quantitative synthesis. Eradication rate in patients receiving levofloxacin and clarithromycin were 75% and 66.3%, respectively (OR: 1.76; 95% CI: 1.40-2.20). In addition, in the subgroup analysis, it was confirmed that cure rate is relatively higher in levofloxacin-treated cases. However, there is significant heterogeneity as well as publication bias, thus, the results need to be interpreted with caution. Conclusions We found that the success of levofloxacin treatment was significantly higher than that of clarithromycin. Therefore, it is suggested that clarithromycin-based triple therapy be replaced by levofloxacin-based triple therapy in countries with high resistance rate to clarithromycin such as Iran. Nevertheless, findings of the present study need to be approved with larger investigation on Iranian population.

Background: Infections with multidrug-resistant Gram-negative bacteria such as Acinetobacter baumannii are major cause of morbidity and mortality. Colistin is used commonly to treat these infections. In this study, we evaluated the efficacy of different colistin combinations in a A. baumannii infection mouse model. Materials & methods: An A. baumannii mouse infection model was developed in 150 experimental animals. Treatment groups were as follows: colistin, colistin + rifampicin, colistin + trimethoprim/sulfamethoxazole, colistin + teicoplanin and a control group. The outcome was bacterial burden in the lung and liver tissues. The treatment groups were subdivided into 24-, 48- and 72-h groups. Results: Colistin and combinations reduce the A. baumannii burden significantly in lung and liver tissues compared with the control group. Compared with colistin alone colistin + rifampicin and colistin + TMP-SMX provided significantly better reduction in the bacterial burden. Conclusion: These results may suggest that rifampicin and TMP-SMX combination with colistin may have a potential role in the treatment of A. baumannii infections.