New Insights into Lamellar Twisting in Transcrystalline Polyethylene

Summary: The morphology of the transcrystalline layer grown by nucleating high density polyethylene on fibers of ultra high molecular weight polyethylene was investigated by microbeam synchrotron X‐ray diffraction. Scanning with a 2 micron step size, it was possible to determine that near the fiber surface, the polymer chains of the transcrystalline layer are oriented at an angle of approx. 41° with respect to the fiber axis. This is consistent with the lamellar fold surface (the {201} plane) being close to perpendicular to the fiber axis. The X‐ray data support gradual twisting of the lamellae about the growth direction (the orthorhombic crystallite b‐axis) at a rate of ～0.85° per micron of radial distance from the fiber surface.

Polarized light micrograph of the transcrystalline layer in a PE/PE composite. The width of the fiber is approximately 20 μm.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

1. Download : Download high-res image (202KB)
2. Download : Download full-size image

     

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4⁺ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4⁺ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from αβ T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4⁺ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-γ.     

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5′-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month

Summary Eighteen patients with advanced solid cancer were treated with daily 5-dFUrd infusions given over 1 h on days 1–5 of a 4-week cycle. Nine patients received 3 g/m² 5-dFUrd daily and another nine patients 5 g/m². One patient on 5 g/m² 5-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1–2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m² 5-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m² group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5-dEUrd and its metabolites 5-FU and 5-dFUH₂ have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5-dFUrd at the end of the infusion approximated 500 mol/l and 1000 mol/l for the 3 g/m² and 5 g/m² group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2–3 compared with the direct injection of 5-FU.Monthly infusion of 5-dFUrd 5 mg/m² per day on days 1–5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5-dFUrd 3 g/m² per day on days 1–5 were well tolerated.     

The Potential of Anti-Bullying Efforts to Prevent Academic Failure and Youth Crime. A Case Using the Olweus Bullying Prevention Program (OBPP)

Prevention Science - The effectiveness of bullying prevention programs has led to expectations that these programs could have effects beyond their primary goals. By reducing the number of victims...     

Belatacept Conversion Protocols and Outcomes in Kidney Transplant Recipients

BackgroundConversion from calcineurin inhibitor (CNI)-based to belatacept-based immunosuppression has become common; however, numerous protocols have emerged in lieu of a standardized protocol. The purpose of this study was to characterize belatacept conversion protocols from multiple centers and observe outcomes.MethodsThis was a retrospective study that included Kaiser Permanente Southern California members. The primary outcome was rejection 6 months after conversion and secondary outcomes included change in serum creatinine and graft loss.ResultsSeventy-eight patients were included. Thirteen distinct protocols were identified from 8 different transplant centers. Protocols varied by initial dose, induction schedule, and CNI taper. The observed rate of rejection was 6%. There was a trend toward an association of rejection with lower tacrolimus exposure at the time of conversion and lower mycophenolic acid dosing postconversion. Graft survival was 88% and patient survival was 94%. There was a significant improvement in creatinine after conversion. Those with early conversions and creatinine >2.0 mg/dL at the time of conversion had the best response.ConclusionsA large variety of belatacept conversion protocols were identified. Protocols were defined by the initial dose, induction regimen, and CNI taper. Rejection rates were low and may be influenced by exposure to maintenance immunosuppression during and after conversion. Most patients showed stabilization and improvement in creatinine postconversion, with the largest effect in those with an early conversion and serum creatinine >2.0 mg/dL.     

Bladder preservation versus radical cystectomy in transitional cell carcinoma and squamous cell carcinoma muscle invasive bladder cancer

Background:Randomizing patients to bladder preservation or radical cystectomy (RC) for the treatment of bladder cancer has not been practical, due to patient and physician preferences. Therefore, continually comparing the 2 treatment modalities is needed, in order to make the proper choice for each patient.Patients and methods:The records of T1–4N0M0 bladder cancer patients, who presented to the South Egypt Cancer Institute between 2007 and 2017 and were treated by either bladder preservation or RC were reviewed.Results:Out of the 166 included patients, 81 (48.8%) patients were treated by bladder preservation and 85 (51.2%) patients had RC. For the patients treated by bladder preservation and the patients treated by RC, the 5-year overall survival (OS) was 56% and 60% (p = 0.67), the 5-year local recurrence-free survival was 69% and 73% (p = 0.69), and the 5-year disease-free survival was 45% and 53% (p = 0.16), respectively. After propensity matching analysis, the mean 5-year OS was 58% for the bladder preservation patients and 61% for the RC patients (p = 0.51). It is notable that among the bladder preservation group, 8 patients (10%) had squamous cell carcinoma (SCC) pathology and refused RC. Their OS was 56% compared to 53% for the SCC patients treated by RC (p = 0.6).Conclusion:Bladder preservation is a safe alternative to cystectomy in transitional cell carcinoma stages T1–4aN0M0, and its use in SCC bladder cancer should be further studied, as it could be feasible to spare them from initial cystectomy.     

The Association Between Neighborhood Social Vulnerability and COVID-19 Testing,Positivity, and Incidence in Alabama and Louisiana

Racial/ethnic and socioeconomic disparities in COVID-19 burden have been widely reported. Using data from the state health departments of Alabama and Louisiana aggregated to residential Census tracts, we assessed the relationship between social vulnerability and COVID-19 testing rates, test positivity, and incidence. Data were cumulative for the period of February 27, 2020 to October 7, 2020. We estimated the association of the 2018 Social Vulnerability Index (SVI) overall score and theme scores with COVID-19 tests, test positivity, and cases using multivariable negative binomial regressions. We adjusted for rurality with 2010 Rural–Urban Commuting Area codes. Regional effects were modeled as fixed effects of counties/parishes and state health department regions. The analytical sample included 1160 Alabama and 1105 Louisiana Census tracts. In both states, overall social vulnerability and vulnerability themes were significantly associated with increased COVID-19 case rates (RR 1.57, 95% CI 1.45–1.70 for Alabama; RR 1.36, 95% CI 1.26–1.46 for Louisiana). There was increased COVID-19 testing with higher overall vulnerability in Louisiana (RR 1.26, 95% CI 1.14–1.38), but not in Alabama (RR 0.95, 95% CI 0.89–1.02). Consequently, test positivity in Alabama was significantly associated with social vulnerability (RR 1.66, 95% CI 1.57–1.75), whereas no such relationship was observed in Louisiana (RR 1.05, 95% CI 0.98–1.12). Social vulnerability is a risk factor for COVID-19 infection, particularly among racial/ethnic minorities and those in disadvantaged housing conditions without transportation. Increased testing targeted to vulnerable communities may contribute to reduction in test positivity and overall COVID-19 disparities.