Experimental model for testing the efficiency of immunotoxins administered in vivo: evaluation of two ricin A-chain — multivalent antibody immunotoxins

Two immunotoxins, the ricin A chain-multivalent hybrid antibody (750 kDa) and the complex A chain-staphylococcal protein A-rabbit IgG antibody (370 kDa), were prepared. A simple method was elaborated to test the immunotoxins' efficiency in selectively killing target cells in tumor-bearing mice. The target cell (murine EL4 leukemia) was coated with a xenogenic molecule by a method conserving its ability to proliferate and kill the inoculated animals. When the challenged animals were treated with these immunotoxins, which were specific for the antigenic molecule coating the tumor cells, survival time was lengthened compared with that of untreated animals, corresponding to a proportion of over 90% cells killed. This demonstrates the efficiency of the immunotoxins and the validity of the method elaborated.     

Are new generations of female college-student populations meeting calcium requirements: comparison of American and Croatian female students

We compared calcium (Ca) sources and intake, as well as multivitamin/mineral supplement use between female students with nutrition/health background and those from general-student-populations. 314 participants 18-37 y, including 57 African-Americans and 54 Caucasian-Americans recruited from Nutrition and/or other Health Sciences departments (NHS), and 100 African-American and 103 Croatian women representing general-student-population (GSP), completed food frequency questionnaire assessing their usual Ca intake and supplement use. NHS populations met recommendations and consumed significantly more Ca, particularly from dairy sources, and were more likely to take supplements than GSP groups, suggesting that health education may influence Ca intake.     

Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study

The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women’s Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66–1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21–3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72–7.83). Total duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion, the association between OC/PMH use and risk of CBC does not differ significantly between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.     

Experimental Investigation on Mechanical and Thermal Properties of Concrete Using Waste Materials as an Aggregate Substitution

The continuous growth of the concrete industry requires an increased quantity of cement and natural aggregates year after year, and it is responsible for a major part of the global CO₂ emissions. These aspects led to rigorous research for suitable raw materials. Taking into account that these raw materials must have a sustainable character and also a low impact on environmental pollution, the replacement of the conventional components of concrete by residual waste can lead to these targets. This paper’s aim is to analyze the density, compressive strength and the thermal conductivity of nine concrete compositions with various rates of waste: four mixes with 10%, 20%, 40% and 60% chopped PET bottles aggregates and 10% fly ash as cement partial substitution; a mix with 60% waste polystyrene of 4–8 mm and 10% fly ash; a mix with 20% waste polystyrene of 4–8 mm, 10% waste polystyrene of 0–4 mm and 10% fly ash; a mix with 50% waste polystyrene of 4–8 mm, 20% waste polystyrene of 0–4 mm and 20% fly ash two mixes with 10% fly ash and 10% and 40% waste sawdust, respectively. Using 60% PET aggregates, 60% polystyrene granules of 4–8 mm, or 20% polystyrene of 0–4 mm together with 50% polystyrene of 4–8 mm led to the obtainment of lightweight concrete, with a density lower than 2000 kg/m³. These mixes also registered the best results from a thermal conductivity point of view, after the concrete mix with 40% saw dust. Regarding compressive strength, the mix with 10% PET obtained a result very close to the reference mix, while those with 20% PET, 40% PET, 30% polystyrene, and 10% saw dust, respectively, registered values between 22 MPa and 25 MPa, values appropriate for structural uses.     

Implementing remotely proctored testing in nursing education

With the recent COVID-19 pandemic, professional nursing education programs across the globe were challenged to transition any face-to-face or hybrid instruction to online. To confront this challenge, many professional nursing education programs explored the option of utilizing remotely proctored testing (RPT). While RPT provides some protection for examination integrity by deterring academic dishonesty, little research is available regarding this examination method which presents unique obstacles. In this climate of technological advancements, faculty of professional nursing programs must prudently consider the advantages of RPT, become familiar with the most commonly occurring issues associated with its use, and carefully integrate the technology to optimize outcomes. In this article, the authors describe the process of integrating RPT into a nursing program along with the outcomes of this integration.     

Phase Ib Study of Enzalutamide with or Without Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Lessons Learned

• Androgen receptor as assessed by immunohistochemistry is expressed in a high proportion of patients with hepatocellular carcinoma (HCC).
• Enzalutamide at 160 mg orally daily is safe and tolerable in patients with advanced HCC but has no single‐agent antitumor activity.
• Enzalutamide, a CYP3A4 inducer, at a standard dose of 160 mg reduces the exposure of sorafenib, a CYP3A4 substrate.
• Enzalutamide and sorafenib is safe and tolerable in patients with advanced HCC, but the addition of enzalutamide to sorafenib did not enhance the antitumor activity of sorafenib.

BackgroundAndrogen receptor (AR) interference is deleterious to hepatocellular carcinoma (HCC) in preclinical models.MethodsThis is a multicenter, phase Ib study of enzalutamide ± sorafenib in patients with advanced HCC. In part 1, a 3 + 3 dose de‐escalation design with expansion established the recommended phase II dose (RP2D) of enzalutamide in patients in whom sorafenib treatment had failed. In part 2, a 3 + 3 dose escalation with expansion established the safety of enzalutamide with sorafenib in treatment‐naive patients with HCC. Secondary objectives included objective response rate (ORR), progression‐free survival (PFS), overall survival (OS), pharmacokinetics (PK), and determination of AR expression by immunohistochemistry. A 7‐day run‐in with sorafenib alone in part 2 allowed assessment of the impact of enzalutamide on sorafenib pharmacokinetics.ResultsIn part 1, 16 patients received enzalutamide 160 mg daily. No dose‐limiting toxicity (DLT) occurred; 1 patient required dose reduction. Responses were not observed; median PFS and OS were 1.8 (95% confidence interval [CI]: 1.6–3.6) and 7 (95% CI: 3.6 to not reached [NR]) months, respectively. In part 2, patients received sorafenib 400 mg daily (4) or twice a day (8) both with enzalutamide at the recommended phase II dose—no DLTs were observed. ORR was 10% (95% CI: 0.3–44.5), and median PFS and OS were 2.9 (95% CI: 1.6 to NR) and 6.7 (95% CI: 4.6 to NR) months, respectively. Enzalutamide reduced sorafenib exposure by 60%. Tumor AR expression did not associate with outcome.ConclusionEnzalutamide is ineffective in HCC; further development is not supported by this study.