Significance of perivesical lymph nodes in radical cystectomy for bladder cancer

ObjectiveThe location of positive lymph nodes (LNs) is important for bladder cancer staging. Little is known regarding the impact of perivesical (PV) lymph node (PVLN) involvement on survival. This study characterized PVLN identified after radical cystectomy (RC) and analyzed their impact on recurrence and survival.Materials and methodsWe reviewed our institutional review board–approved database including all patients who underwent RC with pelvic lymphadenectomy for curative intent for urothelial carcinoma. Clinical and pathologic data were obtained. Patients were analyzed in groups according to the location of positive LNs: PV+/other LN (ON)+, PV+/ON?, and PV?/ON+. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox regression (including pathologic T category, number of positive LNs, highest level of positive LNs, chemotherapy, and margin status) was performed to evaluate associations between PVLN status and survival.ResultsIn total, 2,017 patients met inclusion criteria and 465 (23%) were LN+. PVLNs were identified in 936 patients (47%), positive in 197 patients (10%), and represented isolated LN+disease in 101 patients (5%). On univariate analysis, RFS and OS were significantly worse in the PV+/ON+group compared with the PV+/ON? and PV?/ON+ groups. There were no significant differences in RFS or OS between the PV+/ON? and PV?/ON+ groups. On multivariable analysis, PV+/ON+disease was independently associated with worse RFS and OS when compared with PV?/ON+ disease.ConclusionsPVLNs were identified in a significant number of patients after RC. Positive PVLN, when in combination with other positive LNs, portends worse survival even when correcting for the number of positive nodes.     

Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.     

Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle

Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)–matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n = 6) or with adjuvant alone (n = 6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes.     

Achieved negative differential resistance behavior of Si/B-substituted into a C6 chain sandwiched between capped carbon nanotube junctions

Electronic transport properties of a pristine C₆ chain and Si/B-substituted into the C₆ chain sandwiched between two (5, 5) capped carbon nanotube electrodes were investigated through first-principles calculations based on non-equilibrium Green''s functions (NEGF) conjugated with density functional theory (DFT). Si and B substitutions will affect the I–V curve of a pristine C₆ chain. In the I–V characteristics, multi negative differential resistance (NDR) with large peak to valley ratio (PVR) and rectifying actions were observed. The NDR behavior originates from the joining and moving of conduction orbitals inside and outside of the bias window at a certain bias voltage. Furthermore, the assessment of transmission coefficient and distribution of molecular orbitals reveals that the rectifying performance is the result of the asymmetric distribution of the frontier molecular orbitals in the central region and their coupling with the electrodes. Multi NDR behavior of B substitution under very low bias voltage is a unique property of our proposed devices. Moreover, the CNT|C–(B–C)₂–C|CNT molecular device shows a high PVR up to 31.8, which demonstrates that the proposed devices can be useful for molecular switching in nanoelectronic devices.

Multi negative differential resistance (NDR) with large peak to valley ratio (PVR) and rectifying actions were observed for a CNT|C–(B–C)₂–C|CNT molecular device.     

Spatiotemporal analysis,hotspot mapping,and clustering of confirmed cases of COVID-19 in the initial phase of the pandemic in Qom province,Iran

Objective: To identify the incidence rate, relative risk, hotspot regions and incidence trend of COVID-19 in Qom province, northwest part of Iran in the first s...     

Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD): an Implementation Trial in Eight Veterans Health Administration Facilities

BackgroundIdentifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD.ObjectiveDetermine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls.DesignPre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention.ParticipantsVHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block.InterventionExternal facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation.Main MeasuresPre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities.Key ResultsIntervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: − 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls.ConclusionsIntensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.     

In vivo gene transfer of lefty leads to implantation failure in mice

BACKGROUND: Endometrium is a unique tissue that is prepared for implantation of blastocyst during each menstrual cycle. In humans, if implantation does not occur or fails, endometrium is shed. METHODS AND RESULTS: We identified ebaf/lefty, as a key cytokine, highly expressed in human endometrium during the non-receptive phase of tissue remodelling. Lefty was increased in the endometria of a number of patients with 'unexplained infertility' during the receptive phase, suggesting dysregulation of lefty as a potential factor contributing to infertility. Here, we showed that induction of a similar state of lefty overexpression in endometrium, by in vivo gene delivery, decreased implantation in pregnant mice. This state of overexpression could be induced by a retroviral vector transducing lefty or by liposome-mediated introduction of a lefty expression vector. Analysis of endometrium showed increased lefty after in vivo gene transfer. CONCLUSION: These findings suggest that induction of a state of lefty overexpression in endometrium leads to reduced implantation.