Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.     

In situ polymerization and electrical conductivity of polypyrrole/cellulose nanocomposites using Schweizer's reagent

Cellulose-based composites have attracted interest given the shift towards ‘green’ materials, but achieving uniform dispersions of cellulose in polymer matrices and/or enhancement of interfacial interactions between components remains challenging. Herein we report the preparation of polypyrrole/cellulose nanocomposites in [Cu(NH₃)₄(H₂O)₂](OH)₂ (Schweizer''s reagent/cuoxam)-based reaction media via in situ polymerization. The effect of cellulose template morphology and reaction media on the microstructure, electrical conductivity, and surface wettability was studied. Aqueous reaction media favored the formation of a uniform polypyrrole coating encapsulating the cellulose fibers; concentrated cuoxam solutions promoted inhomogeneity and exhibited a progressive decline in conductivity. The maximum conductivity attained was 3.08 S cm⁻¹ from a bacterial cellulose-templated composite prepared in aqueous reaction media and afforded an approximately threefold increase in conductivity when compared with pure PPy at 1.14 S cm⁻¹. Generally, the composites resembled wetting surfaces – with highly concentrated cuoxam solutions yielding improved hydrophilicity, while substitution of bacterial cellulose with nanocrystalline cellulose engendered a shift towards hydrophobicity. Most composites displayed a contact angle of less than 90° suggesting PPy/cellulose composites tended towards hydrophilic behavior. This study highlights investigations into the viability of cellulose solvents as a facile means to control the structure and performance of in situ functionalized cellulose nanocomposites.

The in situ polymerization of polypyrrole/cellulose nanocomposites using Schweizer''s reagent is demonstrated and measured against a number of structural, electrical, and colligative properties.     

Risk Factors for SARS-CoV-2 Infection and Illness in Cats and Dogs

We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% (1/49) of swab specimens from dogs and 7.7% (5/65) from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners’ beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% (35/221); in shelter samples, 9.3% (7/75). Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill.     

Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach

OBJECTIVEIn a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT).RESEARCH DESIGN AND METHODSLatent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and β-cell function were estimated by glucose, insulin, and C-peptide modeling.RESULTSFour latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and β-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and β-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in β-cell glucose sensitivity.CONCLUSIONSWe identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by β-cell glucose sensitivity.     

On the horizon:Hedgehog signaling to heal broken bones

Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh(Hedgehog) pathway can promote cartilage ...