In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging.

KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [67Ga]KP46 and [68Ga]KP46, compared with [68Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. 68Ga was more efficiently accumulated in A375 cells in vitro when presented as [68Ga]KP46 than as [68Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [68/67Ga]KP46, absorption of 68Ga and 67Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.

Prevalence of musculoskeletal disorders, working conditions, and related risk factors in the meat processing industry: Comparative analysis of Iran-Poland.

BACKGROUND: Activities performed by people in the meat processing industry are very repetitive, time-consuming, dangerous, and require long-term downtime during a shift (forced-static position). OBJECTIVES: This study aims to assess the prevalence of musculoskeletal disorders and working conditions among Polish and Iranian workers to fill this research gap. METHODS: A comparative analysis of the prevalence of musculoskeletal disorders (MSDs) in developed and developing countries was conducted. After selecting the target factories, data was collected using Nordic and Mental Stress Questionnaires and 3DSSPP software with the participation of 110 meat processing workers, including 55 Iranian and 55 Polish. RESULTS: This study showed nearly the same prevalence of MSDs among male Iranian and Polish workers, especially in elbow, wrist/hand, upper back, hip/thigh, and ankle/foot. The overall prevalence of MSDs was relatively high and connected to the lower back (38%, 64%), knee (40%, 24%), neck (24%, 42%), and upper back (24%, 34.5%), among Iranian and Polish workers, respectively. Assessment of logistic regression disclosed that the workplace is considerably associated with the elbow and the ankle/foot musculoskeletal pain, with 2.34 and 3.81 times more likely for the production room, respectively, among Iranian workers. CONCLUSION: Age, gender, type of occupation, work experience, smoking, insufficient physical activity, workplace, working postures, and stress level all affected the likelihood of MSDs happening in various body regions in both countries, implying that both individual and work-related (both physical and psychosocial) aspects should be taken into consideration when evaluating and managing such complaints in this workforce.

Imaging zinc trafficking in vivo by positron emission tomography with zinc-62.

Non-invasive imaging techniques to dynamically map whole-body trafficking of essential metals in vivo in health and diseases are needed. Despite 62Zn having appropriate physical properties for positron emission tomography (PET) imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via 62Cu (half-life, 10 min; positron emission, 97%) has limited its use. We aimed to develop a method to extract 62Zn from a 62Zn/62Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. 62Zn prepared by proton irradiation of natural copper foil was used to construct a conventional 62Zn/62Cu generator. 62Zn was eluted using trisodium citrate and used for biological experiments, compared with 64Cu in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. [62Zn]Zn-citrate was readily eluted from the generator with citrate buffer. PET imaging with the eluate demonstrated biodistribution similar to previous observations with the shorter-lived 63Zn (half-life 38.5 min), with significant differences compared to [64Cu]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post-injection). Between 4 and 24 h, 62Zn retention in liver, pancreas, and kidney declined over time, while brain uptake increased. Like 64Cu, 62Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Although it offers limited reliability of scanning before 1 h post-injection, 62Zn-PET allows investigation of zinc trafficking in vivo for >24 h and hence provides a useful new tool to investigate diseases where zinc homeostasis is disrupted in preclinical models and humans.

A worldwide survey on the use of animal-derived materials and reagents in scientific experimentation.

The use of cell and tissue-based methods in basic, applied and regulatory science has been increasing exponentially. Animal-derived components, including serum, coating materials, growth factors and antibodies are routinely used in cell/tissue cultures and in general laboratory practices. In addition to ethical issues, the use and production of animal-derived materials and reagents raises many scientific concerns, generally associated with presence of undefined components and batch-to-batch variability, which may compromise experimental reproducibility. On the other hand, non-animal materials and reagents, such as human cells, alternatives to animal sera or non-animal recombinant antibodies, are becoming increasingly available, and their use is encouraged by the EU Directive 2010/63 and the Guidance Document on Good In vitro Method Practices (GIVIMP), published by the Organization for Economic Cooperation and Development (OECD). In an effort to map the current state of use of animal-derived reagents across different sectors and to identify the obstacles possibly hampering the implementation of non-animal derived alternatives, a global online survey addressed to scientists working on in vivo, in vitro, in silico methods, in academia as well as pharmaceutical or cosmetic companies, was conducted with the goal to understand: 1) the most commonly used animal-derived materials and reagents, 2) the main issues associated with the production and use of animal-derived materials and reagents, 3) the current level of knowledge on available non-animal alternative materials and reagents, and 4) what educational and information sources could be most useful or impactful to disseminate knowledge on non-animal alternatives. This paper provides an overview of the survey replies and discusses possible proposals to increase awareness, acceptance and use of non-animal ingredients.

Evaluation of working conditions, work postures, musculoskeletal disorders and low back pain among sugar production workers.

BACKGROUND: It is generally agreed that musculoskeletal disorders (MSDs) are a severe health concern, particularly for agricultural laborers. OBJECTIVES: The study aimed to identify risk factors and work-related disorders among agricultural workers at Amirkabir agro-industry company in Iran. METHOD: A total of 158 workers, of which 66 were manual harvesting workers (four postures), 40 were fertilizer transportation workers (three postures), and 52 were spraying workers (one posture), were included in the study. The research used questionnaires to collect data, and the postures were analyzed using 3DSSPP software. Related risk factors such as age, body mass index, work experience, working hours, and sports activity were analyzed. RESULTS: The incidence rate of lower back pain (94%), knee pain (82%), neck pain (69%), upper-back (63%), and shoulder (63%) were calculated. The logistic regression revealed that working hours and sports activities are significantly correlated to the wrist/hand and neck MSD with 5.62 and 6.38 times more likely among manual harvesting workers. The 3DSSPP software estimated that the lower back pain, especially in the first posture, for manure transportation workers was very high. Maximum L5-S1 compression, shear, and moment forces in the first posture among manure transportation workers were 7113 N and 472 N, -381 N-m, respectively. CONCLUSION: The 3DSSPP results also illustrated that compression, shear, and moment forces exceeded the NIOSH limit for the other postures. After interventions, compression, shear, and moment forces among all farm workers decreased. These findings emphasize that farm workers need to be under surveillance continuously at their workstations where interventions and improvement in specific tasks are required.

Non-invasive radionuclide imaging of trace metal trafficking in health and disease: "PET metallomics".

Several specific metallic elements must be present in the human body to maintain health and function. Maintaining the correct quantity (from trace to bulk) and location at the cell and tissue level is essential. The study of the biological role of metals has become known as metallomics. While quantities of metals in cells and tissues can be readily measured in biopsy and autopsy samples by destructive analytical techniques, their trafficking and its role in health and disease are poorly understood. Molecular imaging with radionuclides - positron emission tomography (PET) and single photon emission computed tomography (SPECT) - is emerging as a means to non-invasively study the acute trafficking of essential metals between organs, non-invasively and in real time, in health and disease. PET scanners are increasingly widely available in hospitals, and methods for producing radionuclides of some of the key essential metals are developing fast. This review summarises recent developments in radionuclide imaging technology that permit such investigations, describes the radiological and physicochemical properties of key radioisotopes of essential trace metals and useful analogues, and introduces current and potential future applications in preclinical and clinical investigations to study the biology of essential trace metals in health and disease.

Evaluation of the Effectiveness of Employers and H&S Services in Relation to the COVID-19 System in Polish Manufacturing Companies.

With the advent of the COVID-19 pandemic, companies had to adapt quickly to survive in the market. During this time, employers played a key role, along with employees involved in Occupational Health and Safety (OHS) activities, as they were responsible for implementing the recommendations of the European Commission. There is no unambiguous definition of OHS in Polish legislation. It is assumed that it is a set of rules defining the manner of performing work, and above all, a method of providing employees with working conditions so that their performance is safe and hygienic. Responsibility for the health and safety in the workplace is imposed on the employer by the legislature. Thus, effective health and safety training is an essential element of the success of any properly operating company. In the literature, no studies have been identified that evaluate the effectiveness of actions during the COVID-19 outbreak. The aim of the article is to present the actions of Polish employers along with their effectiveness assessment related to the protection of employees during the COVID-19 outbreak. The article presents a proposal for conducting remote OHS (Occupational Health and Safety) training using the platform Moodle. The created course was implemented during OHS training conducted in a selected manufacturing company. At its end, an evaluation of the course was carried out, and the collected opinions of training participants allowed the formulation of interesting conclusions, which became the contribution of this paper. The authors pay special attention to three main points of the work. The first is the form of training, which gives the possibility to conduct training at a distance while maintaining its effectiveness. The second important point is the mandatory feedback of the trainees, ensuring the possibility of continuous improvement and quality enhancement of both the program and the form of training. The evaluation was developed on the basis of the extended Kirkpatrick model, which is a completely new approach to OHS training evaluation. The third point emphasized by the authors is the possibility of precise adaptation of the training to other plants and even industries. Therefore, it can be concluded that the course developed by the authors is a very interesting and practical didactic tool with great implementation potential.

L-Cysteine-mediated modulation of copper trafficking in prostate cancer cells: an in vitro and in vivo investigation with 64Cu and 64Cu-PET.

Copper imbalance is implicated in many diseases, including cancer. Copper in blood is mainly transported by carrier proteins but a small fraction is bound to low molecular weight species, possibly amino acids. Their roles in cellular copper delivery are unknown. Our aim was to test whether accumulation of 64Cu into cancer-derived cells can be influenced by copper-binding serum amino acids. In vitro cellular accumulation of 64Cu was measured in Hank's Balanced Salt Solution in the presence of 100 µM l-histidine, l-methionine, l-cysteine and l-threonine. l-Cysteine markedly increased 64Cu accumulation and retention in DU145, PC3 and SK-OV-3 cells, while some other cell lines did not show an effect. This effect was not due to 64Cu delivery in the form of a 64Cu-cysteine complex, nor to reduction of 64Cu(ii) to 64Cu(i) by l-cysteine. Pre-incubation of cells with l-cysteine increased 64Cu accumulation, even if l-cysteine was removed from HBSS before 64Cu was added. The effect of l-cysteine on 64Cu accumulation was not mediated by increased glutathione synthesis. Despite the demonstrable in vitro effect, pre-injection of l-cysteine precursor N-acetyl-cysteine (NAC) in vivo did not enhance 64Cu delivery to DU145 xenografts in mice. Instead, it decreased 64Cu accumulation in the DU145 tumour and in brain, as assessed by PET imaging. We conclude that 64Cu is not delivered to DU145 cancer cells in vitro as a complex with amino acids but its cellular accumulation is enhanced by l-cysteine or NAC influx to cells. The latter effect was not demonstrable in vivo in the DU145 xenograft.

Insights into Trace Metal Metabolism in Health and Disease from PET: "PET Metallomics".

Essential trace metals such as copper, zinc, iron, and manganese perform critical functions in cellular and physiologic processes including catalytic, regulatory, and signaling roles. Disturbed metal homeostasis is associated with the pathogenesis of diseases such as dementia, cancer, and inherited metabolic abnormalities. Intracellular pathways involving essential metals have been extensively studied but whole-body fluxes and transport between different compartments remain poorly understood. The growing availability of PET scanners and positron-emitting isotopes of key essential metals, particularly 64Cu, 63Zn, and 52Mn, provide new tools with which to study these processes in vivo. This review highlights opportunities that now present themselves, exemplified by studies of copper metabolism that are in the vanguard of a new research front in molecular imaging: "PET metallomics."

An ergonomics study on wrist posture when using laparoscopic tools in four techniques in minimally invasive surgery.

PURPOSE: With reference to four minimally invasive surgery (MIS) cholecystectomies, the aims were (a) to recognize the factors influencing dominant wrist postures manifested by the surgeon; (b) to detect risk factors involved in maintaining deviated wrist postures; (c) to compare the wrist postures of surgeons while using laparoscopic tools. METHODS: Video films were recorded during live surgeries. The films were synchronized with wrist joint angles obtained from wireless electrogoniometers placed on the surgeon's hand. The analysis was conducted for five laparoscopic tools used during all surgical techniques. RESULTS: The most common wrist posture was extension. In the case of one laparoscopic tool, the mean values defining extended wrist posture were distinct in all four surgical techniques. For one type of surgical technique, considered the most beneficial for patients, more extreme postures were noticed regarding all laparoscopic tools. We recognized a new factor, apart from the tool's handle design, that influences extreme and deviated wrist postures. It involves three areas of task specification including the type of action, type of motion patterns and motion dynamism. CONCLUSIONS: The outcomes proved that the surgical technique which is best for the patient imposes the greatest strain on the surgeon's wrist. .

Advantages and Disadvantages of 1-Incision, 2-Incision, 3-Incision, and 4-Incision Laparoscopic Cholecystectomy: A Workflow Comparison Study.

A comparison of 1-port, 2-port, 3-port, and 4-port laparoscopic cholecystectomy techniques from the point of view of workflow criteria was made to both identify specific workflow components that can cause surgical disturbances and indicate good and bad practices. As a case study, laparoscopic cholecystectomies, including manual tasks and interactions within teamwork members, were video-recorded and analyzed on the basis of specially encoded workflow information. The parameters for comparison were defined as follows: surgery time, tool and hand activeness, operator's passive work, collisions, and operator interventions. It was found that 1-port cholecystectomy is the worst technique because of nonergonomic body position, technical complexity, organizational anomalies, and operational dynamism. The differences between laparoscopic techniques are closely linked to the costs of the medical procedures. Hence, knowledge about the surgical workflow can be used for both planning surgical procedures and balancing the expenses associated with surgery.