Activity

  • McGinnis Raymond posted an update 5 months, 3 weeks ago

    Robotic-assisted FURS have shown good safety and ergonomics in clinical application.

    We investigated compensatory structural hypertrophy and functional hyperfiltration in patients with renal cell carcinoma (RCC) after radical nephrectomy (RN) according to the presence of proteinuria.

    We retrospectively enrolled 471 patients who underwent RN for RCC between October 2005 and December 2013. These patients were divided into two groups according to the presence of postoperative proteinuria (trace or greater (≥1+) urine dipstick). We obtained computed tomography images before and 1 year after surgery to calculate the functional renal volume (FRV). The preoperative and postoperative Chronic Kidney Disease Epidemiology Collaboration equation-calculated glomerular filtration rates (CKD-EPI GFRs) per unit FRV (GFR/FRV) were used to calculate the degree of hyperfiltration.

    The mean patient age was 54.7±11.1 years, and the mean preoperative CKD-EPI GFR, FRV, and GFR/FRV were 89.3±13.3 mL/min/1.73 m

    , 357.2±71.8 cm

    , and 0.26±0.05 mL/min/1.73 m

    /cm

    , respectively. The percentage reduction rate of the GFR was not significantly different according to the presence of proteinuria (normal -28.5±11.6% vs proteinuria -28.7±15%; p=0.902); however, the postoperative hypertrophic FRV in the remnant kidney was significantly different (normal 17.5±9.1% vs proteinuria 13.8±14.1%; p=0.001). Meanwhile, the change in the percentage rate of the GFR/FRV was not significantly different (normal 21.1±23% vs proteinuria 23.8±28.3%; p=0.324). Multivariate logistic regression analysis revealed that age (p=0.010) and the GFR/FRV (p<0.001) were significant predictors of postoperative proteinuria.

    Compensatory structural hypertrophy and functional hyperfiltration are positive adaptations that reduce the occurrence of proteinuria.

    Compensatory structural hypertrophy and functional hyperfiltration are positive adaptations that reduce the occurrence of proteinuria.The survival outcomes for multiple myeloma have improved several-fold in the past two decades, primarily due to the introduction of therapies with novel mechanisms of action including immunomodulatory agents, proteasome inhibitors, stem cell transplant and monoclonal antibodies in the schema of therapy. Antibody-based therapies targeting the surface marker CD38, namely daratumumab and isatuximab, have emerged as being highly effective as single agents as well as in combination regimens for both newly diagnosed and relapsed settings. Herein, the authors summarize the most recent data with both the current and emerging CD38-directed therapies in multiple myeloma.Florfenicol is widely used to control respiratory diseases and intestinal infections in food animals. However, there are increasing reports about florfenicol resistance of various clinical pathogens. floR is a key resistance gene that mediates resistance to florfenicol and could spread among different bacteria. Here, we investigated the prevalence of floR in 430 Pseudomonas aeruginosa isolates from human clinical samples and identified three types of floR genes (designated floR, floR-T1 and floR-T2) in these isolates, with floR-T1 the most prevalent (5.3%, 23/430). FloR-T2 was a novel floR variant identified in this study, and exhibited less identity with other FloR proteins than FloRv. Moreover, floR-T1 and floR-T2 identified in P. Selleckchem Talazoparib aeruginosa strain TL1285 were functionally active and located on multi-drug resistance region of a novel incomplete Tn4371-like integrative and conjugative elements (ICE) in the chromosome. The expression of the two floR variants could be induced by florfenicol or chloramphenicol. These results indicated that the two floR variants played an essential role in the host’s resistance to amphenicol and the spreading of these floR variants might be related with the Tn4371 family ICE.Sulfate Transport Anti-Sigma antagonist domains (Pfam01740) are found in all branches of life, from eubacteria to mammals, as a conserved fold encoded by highly divergent amino acid sequences. These domains are present as part of larger SLC26/SulP anion transporters, where the STAS domain is associated with transmembrane anchoring of the larger multidomain protein. Here, we focus on STAS Domain only Proteins (SDoPs) in eubacteria, initially described as part of the Bacillus subtilis Regulation of Sigma B (RSB) regulatory system. Since their description in B. subtilis, SDoPs have been described to be involved in the regulation of sigma factors, through partner-switching mechanisms in various bacteria such as Mycobacterium. tuberculosis, Listeria. monocytogenes, Vibrio. link2 fischeri, Bordetella bronchiseptica, among others. In addition to playing a canonical role in partner-switching with an anti-sigma factor to affect the availability of a sigma factor, several eubacterial SDoPs show additional regulatory roles compared to the original RSB system of B. subtilis. This is of great interest as these proteins are highly conserved, and often involved in altering gene expression in response to changes in environmental conditions. For many of the bacteria we will examine in this review, the ability to sense environmental changes and alter gene expression accordingly is critical for survival and colonization of susceptible hosts.Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) remains a major public health problem worldwide due in part to the lack of an effective vaccine and to the lengthy course of antibiotic treatment required for successful cure. Combined immuno/chemotherapeutic intervention represents a major strategy for developing more effective therapies against this important pathogen. Because of the major role of CD4+ T cells in containing Mtb infection, augmentation of bacterial specific CD4+ T cell responses has been considered as an approach in achieving this aim. Here we present new data from our own research aimed at determining whether boosting CD4+ T cell responses can promote antibiotic clearance. In these studies, we first characterized the impact of antibiotic treatment of infected mice on Th1 responses to major Mtb antigens and then performed experiments aimed at sustaining CD4+ T cell responsiveness during antibiotic treatment. These included IL-12 infusion, immunization with ESAT-6 and Ag85B immunodominant peptides and adoptive transfer of Th1-polarized CD4+ T cells specific for ESAT-6 or Ag85B during the initial month of chemotherapy. These approaches failed to enhance antibiotic clearance of Mtb, indicating that boosting Th1 responses to immunogenic Mtb antigens highly expressed by actively dividing bacteria is not an effective strategy to be used in the initial phase of antibiotic treatment, perhaps because replicating organisms are the first to be eliminated by the drugs. These results are discussed in the context of previously published findings addressing this concept along with possible alternate approaches for harnessing Th1 immunity as an adjunct to chemotherapy.

    Increasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (

    ). The present study aimed to identify and characterise mcr and other drug-resistant genes in colistin resistant

    clinical isolates.

    Twenty-two colistin resistant

    were analysed for mcr and other drug-resistant genes, efflux pumps, and virulence genes, and for their biofilm forming ability. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed for all

    positive isolates. S1-PFGE and Southern hybridisation were performed for localisation of

    and

    .

    Nineteen colistin resistant

    harboured

    and 3 had

    disruption. All isolates harboured

    -type and ESBL genes; eight strains (five with

    and three with

    disruption) co-harboured

    . Efflux pumps genes

    and

    were detected in all 22 and

    in 21 isolates. Virulence-related genes entB and

    were detected in all 22,

    in 20, and

    in 18 isolates; 11 isolates were strong biofilm producers. PFGE clustered

    positive isolates into eight groups based on ≥90% similarity; MLST revealed diverse sequence types, predominant being ST-15 (n = 4) and ST-16 (n = 4). Both

    and

    were localised on plasmid and chromosome;

    was present on IncFII type and

    on IncFIB and IncA/C type plasmids.

    Colistin resistance in

    was predominantly mediated by

    . Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in

    with ability to emerge as super-spreader of drug-resistance.

    Colistin resistance in K. pneumoniae was predominantly mediated by mcr-1. Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in K. pneumoniae with ability to emerge as super-spreader of drug-resistance.MicroRNA (miRNA or miR)-based approaches to interrupt the transmission of mosquito-borne diseases have been explored since 2005. A review of these studies and areas in which to proceed is needed. In this review, significant progress is reviewed at the level of individual miRNAs, and miRNA diversification and relevant confounders are described in detail. Current miRNA studies in mosquitoes include four steps, namely, identifying miRNAs, validating miRNA-pathogen interactions, exploring action mechanisms, and performing preapplication investigations. Notably, regarding the Plasmodium parasite, mosquito miRNAs generally bind to mosquito immunity- or development-related mRNAs, indirectly regulating Plasmodium infection; However, regarding arboviruses, mosquito miRNAs can bind to the viral genome, directly modifying viral replication. Thus, during explorations of miRNA-based approaches, researchers need select an ideal miRNA for investigation based on the mosquito species, tissue, and mosquito-borne pathogen of interest. Additionally, strategies for miRNA-based approaches differ for arboviruses and protozoan parasites.

    The role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet.

    Analysis was limited to patients that were diagnosed with nodal-only recurrent PC

    PSMA-PET/CT. SLND was performed

    open approach. For SLNRT, dose regimens were normo- or slightly hypo-fractionated with a simultaneous boost to the PET-positive recurrences. EORTC QLQ-C30 and PR-25 questionnaires were used to assess HRQOL. Continence status was assessed using daily pad usage and the validated ICIQ-SF questionnaire. For multivariable analysis, Cox regression models were used (p<0.05).

    138 patients (SLND 71; SLNRT 67) were included in the retrospective analysis. Median follow-up was 47 months (mo) for SLNRT patients (IQR 40-61), and 33mo for SLND patients (IQR 20-49; p<0.001). In total, 61 patients (91.0%) in the SLNRT cohort and 43 patients no significant differences could be observed in MFS, and functional outcomes including HRQOL.Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. link3 Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation.