Dual-targeted magnetic mesoporous silica nanoparticles reduce brain amyloid-ß burden via depolymerization and intestinal metabolism.

Rationale: Active removal of excess peripheral amyloid-ß (Aß) can potentially treat Alzheimer's disease (AD). However, the peripheral clearance of Aß using an anti-Aß monoclonal antibody (mAb) cannot remove PET-detectable Aß within the brain. This may be due to the inability of mAb to cross the blood-brain barrier (BBB) to degrade insoluble brain Aß plaques and block liver dysfunction. Methods: We developed a dual-targeted magnetic mesoporous silica nanoparticle (HA-MMSN-1F12) through surface-coupled Aß42-targeting antibody 1F12 and CD44-targeting ligand hyaluronic acid (HA). Results: HA-MMSN-1F12 had a high binding affinity toward Aß42 oligomers (Kd = 1.27 ± 0.34 nM) and revealed robust degradation of Aß42 aggregates. After intravenous administration of HA-MMSN-1F12 into ten-month-old APP/PS1 mice for three weeks (4 mg/kg/week), HA-MMSN-1F12 could cross the BBB and depolymerize brain Aß plaques into soluble Aß species. In addition, it also avoided hepatic uptake and excreted captured Aß species through intestinal metabolism, thereby reducing brain Aß load and neuroinflammation and improving memory deficits of APP/PS1 mice. Furthermore, the biochemical analysis showed that HA-MMSN-1F12 did not detect any toxic side effects on the liver and kidney. Thus, the efficacy of HA-MMSN-1F12 is associated with the targeted degradation of insoluble brain Aß plaques, avoidance of non-specific hepatic uptake, and excretion of peripheral Aß through intestinal metabolism. Conclusions: The study provides a new avenue for treating brain diseases by excreting disease-causing biohazards using intestinal metabolism.

The need to protect cancer nurses from exposure to hazardous drugs.

Freelance medical writer Christine Clark (chris@salt.u-net.com) reports on an online meeting held in May 2022 as part of a series on the risks of exposure to hazardous drugs for nurses working in oncology.

A Protocol for the Safe Use of Hazardous Drugs in the OR.

Hazardous drug (HD) use in the perioperative environment poses unique challenges and risks for exposure that can have adverse consequences for perioperative personnel. The United States Pharmacopeial Convention has implemented new standards to address the safe handling and administration of HDs by health care workers. To comply with these standards and minimize perioperative personnel's occupational exposure to HDs, a multidisciplinary team at an academic medical center in Boston that was performing an increased number and variety of operative and other invasive procedures using antineoplastic agents updated their protocol for the safe use of HDs in the OR. This article discusses HDs and the risks they pose to health care workers and outlines the new HD safety protocol for the OR that was part of a performance improvement plan to ensure compliance with new standards and staff member safety in the perioperative setting.

Tungsten filled 3D printed field shaping devices for electron beam radiation therapy.

PURPOSE: Electron radiotherapy is a labor-intensive treatment option that is complicated by the need for field shaping blocks. These blocks are typically made from casting Cerrobend alloys containing lead and cadmium. This is a highly toxic process with limited precision. This work aims to provide streamlined and more precise electron radiotherapy by 3D using printing techniques. METHODS: The 3D printed electron cutout consists of plastic shells filled with 2 mm diameter tungsten ball bearings. Five clinical Cerrobend defined field were compared to the planned fields by measuring the light field edge when mounted in the electron applicator on a linear accelerator. The dose transmitted through the 3D printed and Cerrobend cutouts was measured using an IC profiler ion chamber array with 6 MeV and 16 MeV beams. Dose profiles from the treatment planning system were also compared to the measured dose profiles. Centering and full width half maximum (FWHM) metrics were taken directly from the profiler software. RESULTS: The transmission of a 16MeV beam through a 12 mm thick layer of tungsten ball bearings agreed within 1% of a 15 mm thick Cerrobend block (measured with an ion chamber array). The radiation fields shaped by ball bearing filled 3D printed cutout were centered within 0.4 mm of the planned outline, whereas the Cerrobend cutout fields had shift errors of 1-3 mm, and shape errors of 0.5-2 mm. The average shift of Cerrobend cutouts was 2.3 mm compared to the planned fields (n = 5). Beam penumbra of the 3D printed cutouts was found to be equivalent to the 15 mm thick Cerrobend cutout. The beam profiles agreed within 1.2% across the whole 30 cm profile widths. CONCLUSIONS: This study demonstrates that with a proper quality assurance procedure, 3D-printed cutouts can provide more accurate electron radiotherapy with reduced toxicity compared to traditional Cerrobend methods.

Handling of hazardous drugs - Effect of an innovative teaching session for nursing students.

BACKGROUND: Imparting knowledge and practical skills in hazardous drug handling in nursing students' education is essential to prevent hazardous exposure and to preserve nurses' health. OBJECTIVES: This study aimed at comparing routine nursing education with an additional innovative teaching session. DESIGN: A prospective controlled study in nursing students was conducted in two study periods: (i) a status-quo period (routine education on handling hazardous drugs) followed by (ii) an intervention period (additional innovative teaching session on handling hazardous drugs). SETTINGS/PARTICIPANTS: Nursing students at a vocational school were invited to participate voluntarily. METHODS: In both study periods (i) and (ii), the following factors were analysed: (a) knowledge of hazardous drug handling by questionnaire, (b) practical skills in hazardous drug handling (e.g. cleaning) by a simulated handling scenario, (c) contamination with drug residuals on the work surface by fluorescent imaging. RESULTS: Fifty-three nursing students were enrolled. (a) Median knowledge improved from status-quo (39% right answers) to intervention (65%, p<0.001), (b) practical skills improved from status-quo (53% of all participants cleaned the work surface) to intervention (92%, p<0.001). (c) Median number of particles/m2 decreased from status-quo to intervention (932/97, p<0.001). CONCLUSIONS: Compared with routine education, knowledge and practical skills in hazardous drug handling were significantly improved after an innovative teaching session. Additionally, the amount of residuals on the work surface decreased. This indicates a lower risk for hazardous drug exposure.

Cruel disease, cruel medicine: self-treatment of cutaneous leishmaniasis with harmful chemical substances in Suriname.

Why are potentially harmful, non-biomedical chemical substances, such as battery acid, chlorine, herbicides, and insecticides, used in the treatment of cutaneous leishmaniasis (CL)? What drives people to use these products as medicine? This article is about perceptions of CL, and the quest for a cure, in Suriname, South America. It highlights the associative style of reasoning behind health seeking and discusses the use of harmful chemical substances as medicines. Cutaneous leishmaniasis, a parasitic disease, affects 1 to 1.5 million people globally. It has a spectrum of clinical manifestations, but the most prominent and disfiguring elements are extensive dermatological ulceration and scar formation from lesions. The data upon which this article is based are derived from anthropological research carried out in different parts of Suriname between September 2009 and December 2010. Data was collected through mainly qualitative methods, including interviewing 205 CL patients using structured questionnaires at the Dermatological Service in the capital Paramaribo. Almost all people with CL said they tried self-treatment, varying from the use of ethno-botanical products to non-biomedical chemical solutions. This article presents and interprets the views and practices of CL patients who sought treatment using harsh chemicals. It argues that a confluence of contextual factors - environmental, occupational, infrastructural, geographical, socio-cultural, economic, socio-psychological - leads to the use of harmful chemical substances to treat CL sores. This study is the first in Suriname - and one of the few done globally - focusing on social and cultural aspects related to CL health seeking. It aims to encourage health policy makers and health professionals to carefully initiate, provide, and evaluate CL treatment and prevention programs.

Uncertain exposures and the privilege of imperception: activist scientists and race at the U.S. Environmental Protection Agency.

This paper locates the EPA national headquarters within the racialized local geography of southwest Washington, D.C. By focusing on the formation of a scientist union and the union's struggle to make visible an episode of chemical exposure in its own offices, the paper connects the work of racialized privilege with the difficulty of proving chemical exposures in the 1980s.

Use of hazardous substances in the care of rural cancer patients. Current practice standards.

A growing number of rural cancer patients are receiving chemotherapy in hometown clinics and hospitals. Local access to cancer care offers many advantages to patients and providers, but is it safe to give intravenous chemotherapy? What precautions should be taken? Most physicians are well aware of the regulations pertaining to the use of universal precautions to prevent the spread of infectious diseases. A similar approach should be used for hazardous substances. As health care leaders and employers, physicians need to known the risk of exposing employees and themselves to potentially hazardous substances like chemotherapeutic agents. This paper offers current information for physicians to consider when providing cancer care in local health care facilities.