Abstract Context Membranous urethral length (MUL) measured prior to radical prostatectomy (RP) has been identified as a factor that is associated with the recovery of continence following surgery. ...Objective To undertake a systematic review and meta-analysis of all studies reporting the effect of MUL on the recovery of continence following RP. Evidence acquisition A comprehensive search of PubMed, EMBASE, and Scopus databases up to September 2015 was performed. Thirteen studies comprising one randomized controlled trial and 12 cohort studies were selected for inclusion. Evidence synthesis Four studies (1738 patients) that reported hazard ratio results. Every extra millimeter (mm) of MUL was associated with a faster return to continence (hazard ratio: 1.05; 95% confidence interval CI: 1.02–1.08, p < 0.001). Eleven studies (6993 patients) reported the OR (OR) for the return to continence at one or more postoperative time points. MUL had a significant positive effect on continence recovery at 3 mo (OR: 1.08, 95% CI: 1.03–1.14, p = 0.004), 6 mo (OR: 1.12, 95% CI: 1.09–1.15, p < 0.0001). and 12 mo (OR: 1.12, 95% CI: 1.03–1.22, p = 0.006) following surgery. After adjusting for repeated measurements over time and studies with overlapping data, all OR data combined indicated that every extra millimeter of MUL was associated with significantly greater odds for return to continence (OR: 1.09, 95% CI: 1.05–1.15, p < 0.001). Conclusions A greater preoperative MUL is significantly and positively associated with a return to continence in men following RP. Magnetic resonance imaging measurement of MUL is recommended prior to RP. Patient summary We examined the effect that the length of a section of the urethra (called the membranous urethra) had on the recovery of continence after radical prostatectomy surgery. Our results indicate that measuring the length of the membranous urethra via magnetic resonance imaging before surgery may be useful to predict a longer period of urinary incontinence after surgery, or to explain a delay in achieving continence after surgery.
Tenforde et al discuss the report of Lin et al in which they describe a cohort study of 10.6 million people in North Carolina that attempts to disentangle effects of primary and booster vaccination ...from prior infection. Patient demographic characteristics, vaccination history, and SARS-CoV-2 laboratory testing were linked using statewide registries, although many baseline clinical characteristics of individuals were unavailable and outcome measures were missing in a high proportion of patients. Lin et al found that waning of booster dose vaccine effectiveness occurred over 4 to 6 months, but this may be partially due to patients with certain high-risk conditions, such as those who are significantly immunocompromised, getting third doses earlier than the general population. Among individuals who received a primary mRNA vaccine series, understanding comparability between those who received homologous and heterologous mRNA boosters would also be helpful to strengthen inference around benefits of receiving mixed vaccine products that was observed in this study.
Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, ...Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII) specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13), overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid), and lower electrolytic leakage, lipid peroxidation (MDA content) and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To determine if using a digital rectal examination (DRE) human volunteer improves medical students’ confidence in performing DRE in comparison to using a simulated model alone.
...Participants and Methods
Medical students underwent randomization into one of two groups: a control group who underwent standard teaching and an intervention group who underwent standard teaching plus further tuition involving a DRE volunteer. Standard teaching involved a 30‐min lecture and a practice DRE on a simulation model. The intervention group additionally observed a tutor demonstrating DRE on a volunteer, then conducted a DRE themselves under supervision. Before and after teaching, both groups completed a survey comprised of three questions. The primary endpoint was confidence in performing a DRE, which was assessed according to the sum of the scores from the three questions.
Results
In total, 48 students were randomized, 22 to the control group and 26 to the intervention group. The groups were well matched prior to teaching DRE (P = 0.76) After the DRE tutorial, students in the intervention group were more confident in knowing the indications for DRE (P = 0.001), more confident in their technique for performing DRE (P < 0.001) and more confident in their ability to assess findings accurately at DRE (P < 0.001). The primary outcome measure, overall confidence (sum of the scores from all three questions) in performing DRE, was significantly better in the intervention group (score 10/15 vs 14/15; P < 0.001).
Conclusion
This study showed that teaching DRE with the assistance of volunteer patients improves inexperienced students’ confidence in performing DRE, and the incorporation of such training should be considered in the DRE education programme.
Summary Background Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will ...lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. Methods We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. Findings In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80–98) against homotypic strains, 71% (39–86) against partly heterotypic strains, and 87% (76–93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36–73), 72% (58–81), and 47% (28–61). In high-income countries, RV5 vaccine effectiveness was 83% (78–87) against homotypic strains, 82% (70–89) against single-antigen vaccine type strains, 82% (70–89) against partly heterotypic strains, and 75% (47–88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58–78) against single-antigen vaccine type strains, 37% (10–56) against partly heterotypic strains, and 87% (38–97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P4 (2198 of 4428, 50%) and G1P8 (953, 22%), and those in countries using RV5 were G1P8 (1280 of 3875, 33%) and G2P4 (1169, 30%). Sustained predominance of a single strain was not recorded. Interpretation RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. Funding None.
The concept of using viruses to treat cancer has now shown proof of concept in several recent clinical trials, leading to the first FDA approval of virotherapy for melanoma last year. Vesicular ...stomatitis virus (VSV) is a promising oncolytic virus that has inhibitory effects on a number of cancer types including non-small cell lung cancer. One of the major mechanisms of resistance to VSV infection is the type I interferon (IFN) response, leading to the development of VSV expressing IFNβ which will lead to resistance of viral replication in normal cells which have intact IFN signaling but allow replication in cancer cells with defective IFNβ signaling. However, some cancer cells have intact or partially intact IFN signaling pathways leading to resistance to virotherapy. Here we utilized JAK/STAT inhibitor, ruxolitinib, in combination with VSV-IFNβ to see if inhibition of JAK/STAT signaling will enhance VSV-IFNβ therapy for lung cancer. We used five human and two murine NSCLC cell lines in vitro, and the combination treatment was assayed for cytotoxicity. We performed western blots on treated cells to see the effects of ruxolitinib on JAK/STAT signaling and PDL-1 expression in treated cells. Finally, the combination of VSV-IFNβ and ruxolitinib was tested in an immune competent murine model of NSCLC. Ruxolitinib enhanced virotherapy in resistant and sensitive NSCLC cells. The addition of ruxolitinib inhibited STAT1 phosphorylation and to a lesser extent STAT3 phosphorylation. Ruxolitinib treatment prevented NSCLC cells from enhancing PDL-1 expression in response to virotherapy. Combination ruxolitinib and VSV-IFNβ therapy resulted in a trend toward improved survival of mice without substantially effecting PDL-1 levels or levels of immune infiltration into the tumor. These results support further clinical evaluation of the combination of JAK/STAT inhibition with virotherapy.
Obesity is a well-known risk factor for kidney cancer incidence. However, a number of studies have demonstrated more favorable kidney cancer prognosis in patients with elevated body mass index ...conferring a survival advantage, termed the "obesity paradox." We aimed to evaluate the association between body mass index and kidney cancer outcomes (progression-free survival, cancer specific survival and overall survival).
A computerized systematic search of Medline®, Embase®, ProQuest®, PubMed® and Google Scholar™ for literature published in English was performed between its inception and December 2018, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting.
Overall, 34 publications comprising a total of 50,717 patients were included in the analysis. The majority assessed the association between body mass index and cancer specific survival. Overweight and obese patients were associated with improved cancer specific survival compared to patients with normal body mass index (HR 0.85, 95% CI 0.79-0.93). A similar trend was demonstrated for progression-free survival (HR 0.68, 95% CI 0.59-0.78) and overall survival (HR 0.66, 95% CI 0.55-0.79). On the contrary, the underweight group was associated with inferior cancer specific survival (HR 2.16, 95% CI 1.15-4.04). Main drawbacks limiting the interpretation were the retrospective design in the majority of studies, heterogeneity in study population, body mass index classification and covariates in multivariate analysis.
This is the largest systematic review evaluating the potential phenomenon of the obesity paradox in kidney cancer outcomes. It demonstrated a favorable effect of body mass index on kidney cancer outcomes. However, due to significant heterogeneity of studies, multicenter prospective studies and further research on the fundamental biological mechanisms are warranted to confirm the significance of body mass index on kidney cancer prognosis.
A new class of β-aryloxyquinolines
3a–
i and their pyrano3,2-
cchromene derivatives
6a–
r incorporating a validated molecular target has been synthesized
via a nucleophilic displacement and a one-pot ...multicomponent reaction respectively.
In vitro antimicrobial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically
Bacillus subtilis,
Clostridium tetani,
Streptococcus pneumoniae,
Escherichia coli,
Salmonella typhi,
Vibrio cholera,
Aspergillus fumigatus and
Candida albicans. Compounds
3c,
3e,
3g,
6f,
6l and
6q exhibited excellent antibacterial activity while compound
6p exhibited more potent antifungal activity than that of first line standard drugs.
In vitro antituberculosis activity was evaluated against
Mycobacterium tuberculosis H37Rv and compound
6f is emerged as the promising antimicrobial member with better antitubercular activity. Majority of the compounds appears to be better antimicrobials but poor antituberculars.
A series of β-aryloxyquinolines
3a–
3i and their pyrano3,2-
cchromene derivatives
6a–
6r have been synthesized and compared pharmacologically concerning their antimicrobial activities as well as antituberculosis activity against H37Rv.
Display omitted
► A series of β-aryloxyquinolines
3a–
3i and their pyrano3,2-
cchromene derivatives
6a–
6r have been synthesized and compared pharmacologically concerning their antimicrobial activities as well as antituberculosis activity against H37Rv.
Background
To investigate the trends in urinary diversion (UD) in Australia over the past 20 years, to correlate with patient demographics and to compare with international data.
Methods
A ...retrospective analysis of Medicare Australia data was performed using the relevant Medicare Benefit Schedule procedure codes over the past 20 years. Included diversion procedures were ureterocutaneous, ureterocolonic, intestinal conduit and continent reservoir. All patients aged older than 15 years were included in the analyses.
Results
Over the past two decades, 6124 cystectomies and 7166 UDs were subsidized by Medicare Australia. The median age group for UD was 65–74 years old and 71.8% were male. Intestinal conduit accounted for the majority of UDs (84.9%), followed by continent reservoirs (11.8%). Ureterocolonic and ureterocutaneous accounted for small proportions (2.9% and 0.4%, respectively). The absolute numbers of UD procedures increased over the past 20 years but the proportion of different methods remained constant. The rates of continent reservoir UD were significantly higher in men and people aged less than 55 years old (P < 0.001 for both). Over the course of the study, the proportion of people aged greater than 75 years undergoing UD increased significantly (P < 0.001).
Conclusion
In contrast to major international academic institutions, the proportion of continent reservoir UDs performed in Australia has not changed over the past two decades. Intestinal conduit remains the most common UD procedure.
Over the last two decades, the annual number of cystectomies and urinary diversion procedures performed in Australia has been steadily rising. In contrast to major international academic institutions and despite increased experience, the incidence of continent urinary diversion has not increased.
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