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The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour.

Microfluidic paper-based analytical devices (μPADs) are emerging as powerful analytical platforms in clinical diagnostics, food safety, and environmental protection because of their low cost and favorable substrate properties for biosensing. However, the existing top-down fabrication methods of paper-based chips suffer from low resolution (200 μm). Additionally, papers have limitations in their physical properties (e.g., thickness, transmittance, and mechanical flexibility). Here, we demonstrate a bottom-up approach for the rapid fabrication of heterogeneously controlled paper-based chip arrays. We simply print a wax-patterned microchip with wettability contrasts, enabling automatic and selective assembly of cellulose microfibers to construct predefined paper-based microchip arrays with controllable thickness. This paper-based microchip printing technology is feasible for various substrate materials ranging from inorganic glass to organic polymers, providing a versatile platform for the full range of applications including transparent devices and flexible health monitoring. Our bottom-up printing technology using cellulose microfibers as the starting material provides a lateral resolution down to 42 ± 3 μm and achieves the narrowest channel barrier down to 33 ± 2 μm. As a proof-of-concept demonstration, a flexible paper-based glucose monitor is built for human health care, requiring only 0.3 μL of sample for testing.

Food safety is an issue that cannot be ignored at any time because of the great impact of food contaminants on people's daily life, social production, and the economy. Because of the extensive demand for high-quality food, it is necessary to develop rapid, reliable, and efficient devices for food contaminant detection. Microfluidic paper-based analytical devices (μPADs) have been applied in a variety of detection fields owing to the advantages of low-cost, ease of handling, and portability. This review systematically discusses the latest progress of μPADs, including the fundamentals of fabrication as well as applications in the detection of chemical and biological hazards in foods, hoping to provide suitable screening strategies for contaminants in foods and accelerating the technology transformation of μPADs from the lab into the field.

This work presents a unique approach to the design, fabrication, and characterization of paper-based origami robotic systems consisting of stackable pneumatic actuators. These paper-based actuators (PBAs) use materials with high elastic modulus-to-mass ratios, accordion-like structures, and direct coupling with pneumatic pressure for extension and bending. The study contributes to the scientific and engineering understanding of foldable components under applied pneumatic pressure by constructing stretchable and flexible structures with intrinsically nonstretchable materials. Experiments showed that a PBA possesses a power-to-mass ratio greater than 80 W/kg, which is more than four times that of human muscle. This work also illustrates the stackability and functionality of PBAs by two prototypes: a parallel manipulator and a legged locomotor. The manipulator consisting of an array of PBAs can bend in a specific direction with the corresponding actuator inflated. In addition, the stacked actuators in the manipulator can rotate in opposite directions to compensate for relative rotation at the ends of each actuator to work in parallel and manipulate the platform. The locomotor rotates the PBAs to apply and release contact between the feet and the ground. Furthermore, a numerical model developed in this work predicts the mechanical performance of these inflatable actuators as a function of dimensional specifications and folding patterns. Overall, we use stacked origami actuators to implement functionalities of manipulation, gripping, and locomotion as conventional robotic systems. Future origami robots made of paper-like materials may be suitable for single use in contaminated or unstructured environments or low-cost educational materials.

Selective detection and quantification of biomarkers related to human diseases are essential for preventive healthcare. Surface-enhanced Raman scattering (SERS) spectroscopy is a powerful analytical tool offering high sensitivity. However, the success of this promising analytical tool relies on the ability to effectively fabricate SERS substrate. Herein we have demonstrated a plasmonic paper-based flexible substrate (PPFS) for SERS sensing. In situ growth of silver nanostructures (AgNS) on the paper-based substrate was achieved by using a simple one-step silver mirror reaction (SMR). FESEM and TEM results depicts that the increasing silver ion content influences the morphology (growth of multifacets), as well as size of AgNS. Further, the PPFS substrate was tested with Rhodamine-6G (Rh-6G) dye and an attomole sensitivity with a LOD of 4.54 x 10-18 M was achieved. Further, two biomarkers, lactic acid (LA) and uric acid (UA) were detected on the PPFS substrate, with μM and pM sensitivity, having LOD values of 0.6 x 10-6 and 0.3 x 10-12 M respectively. Above detection levels for UA on PPFS is two orders better than reported values, whereas for LA it is comparable with reported substrates. Finally, UA, LA and their mixtures were tested on PPFS and results compared with commercial substrate. The performance of PPFS were found better in all cases, thus, multifaceted AgNS paper based PPFS offers the potential to be used as a biosensor for detection of various biomarkers from body fluids, responsible for the detection of the critical disease for preventive health care.

Introduction The assessment of the risk of virus transmission through papers, such as postcards, is important. However, the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) on different types of papers is currently unknown. Investigation of the survival time of these viruses on different types of papers will provide insights into their risk of long-distance transport by postal items. Methods We evaluated the stability of SARS-CoV-2 and IAV, mixed with a culture medium, on the surface of postcards with various coatings, including plain paper (PP), inkjet paper (IP), and inkjet photo paper (IPP). The surface structure of each paper was microscopically assessed. Results The surface structures of PP, IP, and IPP varied greatly depending on the presence or absence, and type, of coat layer, regardless of the base material. IP and IPP surfaces were less conducive to virus survival than PP surfaces, because of the difference in surface shapes. The survival times of SARS-CoV-2 on each paper were approximately 59.8 (PP), 6.5 (IP), and 9.8 h (IPP), and significantly longer than those of IAV (10.3, 1.8, and 3.3 h, respectively). Conclusions The risk of SARS-CoV-2 transmission via paper, such as postcards, is significantly higher than that of IAV transmission. While PP, IP, and IPP have the same base material, their surface structures differ, which affects viral stability. The IP and IPP surfaces are less suitable for virus survival. This study provides novel insights into the risks of viral transmission via paper.

The INDDEX24 Dietary Assessment Platform (INDDEX24) was developed to facilitate the collection of 24-h dietary recall (24HR) data. Alongside validation studies in Viet Nam and Burkina Faso in 2019–2020, we conducted activity-based costing studies to estimate the cost of conducting a 24HR among women of reproductive age using INDDEX24 compared with the pen-and-paper interview (PAPI) approach. We also modelled alternative scenarios in which: (1) 25–75 % of dietary reference data were borrowed from the INDDEX24 Global Food Matters Database (FMDB); (2) all study personnel were locally based and (3) national-scale surveys. In the primary analysis, in Viet Nam, the 24HR cost US $111 004 ($755/respondent, n 147) using INDDEX24 and $120 483 ($820/respondent, n 147) using PAPI. In Burkina Faso, the 24HR cost $78 105 ($539/respondent, n 145) using INDDEX24 and $79 465 ($544/respondent, n 146) using PAPI. In modelled scenarios, borrowing dietary reference data from the FMDB decreased the cost of INDDEX24 by 17–34 % (Viet Nam) and 5–15 % (Burkina Faso). With all locally based personnel, INDDEX24 cost more than PAPI ($498 v. $448 per respondent in Viet Nam and $456 v. $410 in Burkina Faso). However, at national scales (n 4376, Viet Nam; n 6500, Burkina Faso) using all locally based personnel, INDDEX24 was more cost-efficient ($109 v. $137 per respondent in Viet Nam and $123 v. $148 in Burkina Faso). In two countries and under most circumstances, INDDEX24 was less expensive than PAPI. Higher INDDEX24 survey preparation costs (including purchasing equipment) were more than offset by higher PAPI data entry, cleaning and processing costs. INDDEX24 may facilitate cost-efficient dietary data collection.

The International Conference on Cognitive Modeling brings together researchers from around the world whose main goal is to build computational systems that reflect the internal processes of the mind. In this issue, we present the five best representative papers on this work from our 19th meeting, ICCM 2021, which was held virtually from July 3 to July 9, 2021. Three of these papers provide new techniques for refining computational models, giving better methods for taking empirical data and producing accurate computational models of the cognitive systems that produce them. The other two papers focus on explanation: using models to elucidate the underlying processes affecting cognition in such diverse domains as logical reasoning and the effects of caffeine.

Microfluidic paper-based analytical devices (μPADs) are emerging as prominent platform for disease detection, specifically in developing countries. This paper device offers simplicity and affordability not typically seen in centralized laboratory settings. However, detection limits in μPADs are inadequate and often require tests results to be read within a specific time interval to ensure accuracy. To overcome these challenges, we are developing an on-chip mass spectrometry (MS) detection strategy for immunoassays performed on paper substrates. Herein, we present our initial results from a proof-of-concept study toward the development of μPADs capable of storing immunoassay reagents within the confinements of the 3D device, automatic splitting of biofluid into four individual test zones, immuno-capture of disease biomarker, and on-chip MS detection of captured species. The reported study encourages the development of point-of-care and direct-to-customer testing using the disposable μPAD to collect samples, followed by sensitive analysis using portable mass spectrometers. We demonstrate this capability using malaria Plasmodium falciparum histidine-rich protein 2 (PfHRP2) antigen detection.

Objective The purpose of this study was to develop a natural language processing (NLP) pipeline to identify incidental thyroid nodules (ITNs) meeting criteria for sonographic follow-up and to assess both adherence rates to white paper recommendations and downstream outcomes related to these incidental findings. Methods 21583 non-contrast chest CT reports from 2017 and 2018 were retrospectively evaluated to identify reports which included either an explicit recommendation for thyroid ultrasound, a description of a nodule ≥ 1.5 cm, or description of a nodule with suspicious features. Reports from 2018 were used to train an NLP algorithm called fastText for automated identification of such reports. Algorithm performance was then evaluated on the 2017 reports. Next, any patient from 2017 with a report meeting criteria for ultrasound follow-up was further evaluated with manual chart review to determine follow-up adherence rates and nodule-related outcomes. Results NLP identified reports with ITNs meeting criteria for sonographic follow-up with an accuracy of 96.5% (95% CI 96.2-96.7) and sensitivity of 92.1% (95% CI 89.8-94.3). In 10006 chest CTs from 2017, ITN follow-up ultrasound was indicated according to white paper criteria in 81 patients (0.8%), explicitly recommended in 46.9% (38/81) of patients, and obtained in less than half of patients in which it was appropriately recommended (17/35, 48.6%). Discussion NLP accurately identified chest CT reports meeting criteria for ITN ultrasound follow-up. Radiologist adherence to white paper guidelines and subsequent referrer adherence to radiologist recommendations showed room for improvement.

Microfluidic paper-based analytical devices (microPADs) are emerging as simple-to-use, low-cost point-of-care testing platforms. Such devices are mostly fabricated at present by creating hydrophobic barriers using wax or photoresist patterning on porous paper sheets. Even though devices fabricated using these methods are used and tested with a wide variety of analytes, still they pose many serious practical limitations for low-cost automated mass fabrication for their widespread applicability. We present an affordable and simple two-step process - cut and heat (CH-microPADs) - for the selective fabrication of hydrophilic channels and reservoirs on a wide variety of porous media such as tissue/printing/filter paper and cloth types, such as cotton and polyester, by a lamination process. The technique presents many advantages as compared to existing commonly used methods. The devices possess excellent mechanical strength against bending, folding and twisting, making them virtually unbreakable. They are structurally flexible and show good chemical resistance to various solvents, acids and bases, presenting widespread applicability in areas such as clinical diagnostics, biological sensing applications, food processing, and the chemical industry. Fabricated paper media 96 well-plate CH-microPAD configurations were tested for cell culture applications using mice embryonic fibroblasts and detection of proteins and enzymes using ELISA. With a simple two-step process and minimal human intervention, the technique presents a promising step towards mass fabrication of inexpensive disposable diagnostic devices for both resource-limited and developed regions.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Paper has been widely employed as cheap material for the development of a great number of sensors such as pregnancy tests, strips to measure blood sugar, and COVID-19 rapid tests. The need for new low-cost analytical devices is growing, and consequently the use of these platforms will be extended to different assays, both for the final consumer and within laboratories. This work describes a paper-based electrochemical sensing platform that uses a paper disc conveniently modified with recognition molecules and a screen-printed carbon electrode (SPCE) to achieve the detection of gluten in a deep eutectic solvent (DES). This is the first method coupling a paper biosensor based on aptamers and antibodies with the DES ethaline. Ethaline proved to be an excellent extraction medium allowing the determination of very low gluten concentrations. The biosensor is appropriate for the determination of gluten with a limit of detection (LOD) of 0.2 mg L−1 of sample; it can detect gluten extracted in DES with a dynamic range between 0.2 and 20 mg L−1 and an intra-assay coefficient of 10.69%. This approach can be of great interest for highly gluten-sensitive people, who suffer from ingestion of gluten quantities well below the legal limit, which is 20 parts per million in foods labeled gluten-free and for which highly sensitive devices are essential. Graphical abstract

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is one of the major causes of death and disability worldwide. Higher case-fatality rates and short survival times have been reported in developing countries. Hence, a quick, straightforward, and low-cost approach is in great demand for the diagnosis of meningitis. In this research, a microfluidic fully paper-based analytical device (μFPAD) integrated with loop-mediated isothermal amplification (LAMP) and ssDNA-functionalized graphene oxide (GO) nano-biosensors was developed for the first time for a simple, rapid, low-cost, and quantitative detection of the main meningitis-causing bacteria

Parenteral and enteral nutrition support are key components of care for various medical and physiological conditions in infants, children, and adults. Nutrition support practices have advanced over time, driven by the goals of safe and sufficient delivery of needed nutrients and improved patient outcomes. These advances have been, and continue to be, dependent on research and development studies. Such studies address aspects of enteral and parenteral nutrition support: formulations, delivery devices, health outcomes, cost-effectiveness, and related metabolism. The studies are supported by public funding from the government and by private funding from foundations and from the nutrition support industry. To build public trust in nutrition support research findings, it is important to underscore ethical research conduct and reporting of results for all studies, including those with industry sponsors. In 2019, American Society for Parenteral and Enteral Nutrition's (ASPEN's) Board of Directors established a task force to ensure integrity in nutrition support research that is done as collaborative partnerships between the public (government and individuals) and private groups (foundations, academia, and industry). In this ASPEN Position Paper, the Task Force presents principles of ethical research to guide administrators, researchers, and funders. The Task Force identifies ways to curtail bias and to minimize actual or perceived conflict of interests, as related to funding sources and research conduct. Notably, this paper includes a Position Statement to describe the Task Force's guidance on Public-Private Partnerships for research and funding. This paper has been approved by the ASPEN Board of Directors.

As a crucial biomarker for some diseases, the determination of cholesterol in human serum is of great significance for the diagnosis and prevention of these diseases. Hence, a portable cholesterol detection method is necessary for clinical and domestic applications. Here, a portable paper sensor was designed for cholesterol detection by modifying screen-printed electrode (SPE) with nanoporous gold (NPG). To achieve the reliable cholesterol detection, a synergistic strategy was proposed based on the oxidation of cholesterol by cholesterol oxidase (ChOx) and the reduction of oxidation product (H2O2) by NPG. Compared to existing electrochemical sensors, the resulting paper sensor exhibited a wider linear response in a range from 50 μM to 6 mM as well as a higher sensitivity of 32.68 μA mM−1 cm−2 with a lower detection limit of 8.36 μM. Moreover, the portable paper sensor presented strong anti-interference capability and stability in the detection of cholesterol in human serum, and the data detected by the portable paper sensor were consistent with that obtained by an automatic biochemical analyzer. These unique performances confirmed that the proposed paper sensor was a sensitive, reliable, and portable cholesterol detection method, making it a good choice for cholesterol detection.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.

Graphene paper (GP), a macroscopic self-supporting material, has exceptional flexibility and preserves the excellent physical and chemical properties of graphene nanomaterials. But its applications in regenerative medicine remain to be further explored. Here, we biologically functionalized GP with hydroxyapatite (HA) nanorods by the use of GP-binding peptides as an affinity linker. This strategy solved two daunting challenges for regenerative medicine applications of GP: the lack of good hydrophilicity for supporting cell growth and the difficulty in forming composites by binding with nanobiomaterials. Briefly, we first screened a high-affinity GP-binding peptide (TWWNPRLVYFDY) by the phage display technique. Then we chemically conjugated the GP-binding peptide to the synthetic HA nanorods. The GP-binding peptide on the resultant HA nanorods enabled them to be bound and assembled onto the GP substrate with high affinity, forming a GP-peptide-HA composite with significantly improved hydrophilicity of GP. The composite promoted the attachment and proliferation of mesenchymal stem cells (MSCs), demonstrating its outstanding biocompatibility. Due to the unique compositions of the composite, it was also found to induce osteogenic differentiation of MSCs in vitro in the absence of other inducers in the medium, by verifying the expression of the osteogenic markers including collagen-1, bone morphogenetic proteins 2, runx-related transcription factor 2, osteocalcin, and alkaline phosphatase. Our work suggests that the GP-binding peptide can be used to link inorganic nanoparticles onto GP to facilitate the biomedical applications of GP.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Timely and rapid detection of biomarkers is extremely important for the diagnosis and treatment of diseases. However, going to the hospital to test biomarkers is the most common way. People need to spend a lot of money and time on various tests for potential disease detection. To make the detection more convenient and affordable, we propose a paper-based aptasensor platform in this work. This device is based on a cellulose paper, on which a three-electrode system and microfluidic channels are fabricated. Meanwhile, novel nanomaterials consisting of amino redox graphene/thionine/streptavidin-modified gold nanoparticles/chitosan are synthesized and modified on the working electrode of the device. Through the biotin-streptavidin system, the aptamer whose 5'end is modified with biotin can be firmly immobilized on the electrode. The detection principle is that the current generated by the nanomaterials decreases proportionally to the concentration of targets owing to the combination of the biomarker and its aptamer. 17β-Estradiol (17β-E2), as one of the widely used diagnostic biomarkers of various clinical conditions, is adopted for verifying the performance of the platform. The experimental results demonstrated that this device enables the determination of 17β-E2 in a wide linear range of concentrations of 10 pg mL-1 to 100 ng mL-1 and the limit of detection is 10 pg mL-1 (S/N = 3). Moreover, it enables the detection of targets in clinical serum samples, demonstrating its potential to be a disposable and convenient integrated platform for detecting various biomarkers.

Although crucial in improving health outcomes in the preterm infants, parenteral nutrition (PN) is not without risk, especially if handled improperly. A growing body of evidence suggests that components of PN admixtures, including lipid injectable emulsions (ILEs), are susceptible to degradation, including oxidation when exposed to light (ie, photo-oxidation), resulting in the production of reactive oxygen species. Infants, especially those born preterm, are considered more susceptible to consequences of oxidative stress than children and adults. Oxidative stress is associated with bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intestinal failure-associated liver disease. The American Society for Parenteral and Enteral Nutrition (ASPEN) assembled a working group to provide recommendations on clinical practice surrounding photoprotection of PN.This Position Paper reviews the scientific literature on the formation of quantifiable peroxides and other degradation products when PN admixtures and ILEs are exposed to light and reports adverse clinical outcomes in premature infants exposed to PN. Recommendations for photoprotection of PN admixtures and ILEs are provided, as well as the challenges in achieving complete photoprotection with the equipment, supplies, and materials currently available in the US. ASPEN and the authors understand that the full implementation of complete photoprotection may not currently be feasible given current product availability; recommendations provided in this paper serve to represent the goal to which to strive as well as to highlight the importance of product availability to achieve these practices. This paper has been approved by the ASPEN Board of Directors.

Objectives Paper dust has previously been linked to adverse health effects. However, a comprehensive dataset of paper dust exposures does not appear to have been published previously. Our study was intended to address this need by describing a large dataset of measurements made in Swedish soft tissue paper mills. Methods We compiled personal and area total dust exposure measurements collected from a range of operations by our research staff at four soft tissue paper mills in Sweden. We also compiled measurements made by the occupational health staff at each mill and the Swedish Work Environment Authority. We analyzed these measurements to describe patterns and trends in exposures and used mixed-effects regression models to identify measurement characteristics that predicted exposure levels. Results We compiled 1578 measurements from 1971 to 2009, of which 1026 (65%) were personal samples. Statistically significant differences were found between measurements made by research, mill, and Swedish Work Environment Authority staff, as well as between personal and area measurements. The measurement data suggest that, beginning in the 1980s, exposures declined at three of the four mills, but that overexposures were still common at the end of the period. Papermaking and converting operations had the highest observed dust exposures. One mill had significantly lower exposures than the others. Type of measurement (personal versus area) and source of measurement (research staff, company, or regulatory agency) were not significant predictors of measured total dust exposure after controlling for mill, operation, and time. Conclusions Our analysis of measured paper dust exposures may be useful for historical and contemporary exposure assessment in our own and other epidemiological studies. We have identified specific characteristics (i.e. papermaking operations and mill) and time trends that are important data features to consider, and documented continuing overexposure situations. Our results highlight the ongoing need for application of exposure controls to reduce paper dust exposures in the soft tissue paper industry.

Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

Hypoxia is a nonphysiological oxygen tension which is common in most malignant tumors. Hypoxia stimulates complicated cell signaling networks in cancer cells, e.g., the HIF, PI3K, MAPK, and NFκB pathways. Then, cells release a number of cytokines such as VEGFA to promote the growth of peripheral blood vessels and lead to metastasis. In the current work, understanding of the internal hypoxic environment in solid tumor tissue was attempted by developing a folding paper system. A paper-based solid tumor was constructed by folding a filter paper cultured with cancer cells. The cellular response in each layer could be analyzed by disassembling the folded paper after the culture course. The result showed that an internal hypoxic environment was successfully reproduced in the paper-based solid tumor. The cells in the inner layer expressed high levels of HIF1-α and VEGFA. Hence, proliferation and migration of endothelial cells were shown to be induced by the cells located in the internal hypoxic environment. Moreover, the paper-based solid tumor was transplanted into nude mice for the study of hypoxic response and angiogenesis. The crosstalk between internal and external parts of solid tumor tissue could be analyzed by sectioning each layer of the paper-based solid tumor. This approach provides a favorable analytical method for the discovery of the interaction between cancer cells, hypoxia, and peripheral angiogenesis.

The latest outbreak of a coronavirus disease in 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), evolved into a worldwide pandemic with massive effects on health, quality of life, and economy. Given the short period of time since the outbreak, there are several knowledge gaps on the comparative and zoonotic aspects of this new virus. Within the One Health concept, the current EAACI position paper dwells into the current knowledge on SARS‐CoV‐2’s receptors, symptoms, transmission routes for human and animals living in close vicinity to each other, usefulness of animal models to study this disease and management options to avoid intra‐ and interspecies transmission. Similar pandemics might appear unexpectedly and more frequently in the near future due to climate change, consumption of exotic foods and drinks, globe‐trotter travel possibilities, the growing world population, the decreasing production space, declining room for wildlife and free‐ranging animals, and the changed lifestyle including living very close to animals. Therefore, both the society and the health authorities need to be aware and well prepared for similar future situations, and research needs to focus on prevention and fast development of treatment options (medications, vaccines).

As the most frequently used archival materials for painting and recording, paper lays the groundwork for the development of prosperous human civilization. However, its susceptibility to three primary factors including external ultraviolet light, increased acidity, and biological pathogens in long-term storage shortens the longevity of paper. Therefore, the protection of paper-based cultural relics is extremely urgent. Inspired by the three adverse factors affecting the protection of cultural relics, we herein propose to combine the ultraviolet absorber 2-hydroxy-4-(octyloxy)benzophenone (UV-531) and alkaline zinc oxide (ZnO) nanoparticles innovatively into the antibacterial agent polyhexamethylene biguanidine hydrochloride (PHMB) to realize the strategy of three birds with one stone for relics protection. This study illustrates that the tensile strength and the folding endurance of different test papers are guaranteed by coating them with the composite reagents, and molds including Mucor, Trichoderma, and Aspergillus niger are effectually sterilized. In addition, a hand-painted Chinese ink-wash painting with beautiful flowers is chosen as the object for simulating cultural relics protection, and negligible color fading is observed in aging experiments. From the perspective of effectiveness, simplicity, and economy, this strategy sheds light on preservative protection of paper-based relics in long-term storage.

Objective The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). Study Design The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Results Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Conclusion Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

In this work, indoxyl-glucoside was used as the substrate to develop a cost-effective, paper-based analytical device for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity through a smartphone. The β-glucosidase can hydrolyze the colorless substrate indoxyl-glucoside to release indoxyl, which will be self-oxidized to generate green products in the presence of oxygen. Meanwhile, the green products emit bright blue-green fluorescence under ultraviolet–visible light irradiation at 365 nm. Fluorescent or colorimetric images were obtained by a smartphone, and the red-green-blue channels were analyzed by the Adobe Photoshop to quantify the β-glucosidase activity. Under the optimum conditions, the relative fluorescent and colorimetric signals have a good linear relationship with the activity of β-glucosidase, in the range of 0.01–1.00 U/mL and 0.25–5.00 U/mL, and the limits of detection are 0.005 U/mL and 0.0668 U/mL, respectively. The activities of β-glucosidase in a crude almond sample measured by the fluorescent and colorimetric methods were 23.62 ± 0.53 U/mL and 23.86 ± 0.25 U/mL, respectively. In addition, the spiked recoveries of normal human serum and crude almond samples were between 87.5% and 118.0%. In short, the paper-based device, combined with a smartphone, can provide a simple, environmentally friendly, and low-cost method for the fluorescent and colorimetric dual-mode detection of β-glucosidase activity.

This article reports a simple and inexpensive leak-proof paper pad with an initial selection of a paper substrate on the grounds of surface morphology and fluid absorption time. Herein, a drying method is used for glucose detection on a paper pad through colorimetric analysis, and the spot detection of glucose is analyzed by optimizing the HRP concentration and volume to obtain accurate results. The rapid colorimetric method for the detection of glucose on the paper pad was developed with a limit of detection (LOD) of 2.92 mmol L−1. Furthermore, the effects of the detection conditions were investigated and discussed comprehensively with the help of chemometric methods. Paper pads were developed for glucose detection with a range of 0.5–20 mM (apropos to the normal glucose level in the human body) and 0.1–0.5 M (to test the excessive intake of glucose). The developed concept has huge potential in the healthcare sector, and its extension could be envisioned to develop the reported paper pad as a point-of-care testing device for the initial screening of a variety of diseases.

Carbon fiber paper (CFP) is commonly used as a proton exchange membrane in fuel cells due to its prominent areal electrosorption capacity, exceptional conductivity and excellent chemical stability. In this paper, we first explored the feasibility of carbon fiber paper as a specific paper substrate in paper spray ionization mass spectrometry (PSI-MS). The results demonstrated that CFPSI-MS combines the merits of PSI and carbon fiber ionization (CFI) and exhibits better performance of various compound analyses than either of these techniques alone. The application of CFP can highly enhance the signal stability and detection sensitivity of a diverse array of analytes, especially in negative ionization mode. The ion intensity of target analytes such as saccharides and flavonoids was improved 2-90-fold. Many nonpolar/low-polarity analytes, such as polycyclic aromatic hydrocarbons, which are difficult to ionize by traditional PSI-MS, were successfully detected by CFPSI-MS with a 2.5 kV high voltage. Moreover, CFPSI-MS presents high sensitivity in semiquantitative analysis, and the limits of detection (LODs) of cyclic adenosine monophosphate (CAMP), naringin and tivantinib in whole blood were improved 2-100-fold compared to those in traditional PSI-MS. In real sample analysis, CFPSI-MS also exhibits excellent capability in human breath analysis and blood metabolomic profiling.

In vitro epidermis models are important to evaluate and study disease progression and possible dermal drug delivery. An in vitro epidermis model using floating paper chips as a scaffold for proliferation and differentiation of primary human keratinocytes is reported. The formation of the four main layers of the epidermis (i.e., basal, spinosum, granulose, and cornified layers) is confirmed. The development of a cornified layer and the tight junction formation are evaluated as well as the alterations of organelles during the differentiation process. Further, this in vitro model is used to assess keratinocyte migration. Finally, magnetic micromotors are assembled, and their ability to aid cell migration on paper chips is confirmed when a static magnetic field is present. Taken together, this attempt to combine bottom-up synthetic biology with dermatology offers interesting opportunities for studying skin disease pathologies and evaluate possible treatments.

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

Urinary incontinence is a common problem among older adults that is often complicated by many nuanced ethical considerations. Unfortunately, there is a lack of guidance for healthcare professionals on how to navigate such concerns. This International Continence Society white paper aims to provide healthcare professionals with an ethical framework to promote best care practices in the care of older adults with urinary incontinence.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

Technologic advancements and the evolving digital health landscape have offered innovative solutions to several of our health care system's issues as well as increased the number of digital interactions and type of personal health information that is generated and collected, both within and outside of traditional health care. This American College of Physicians' position paper discusses the state of privacy legislation and regulations, highlights existing gaps in health information privacy protections, and outlines policy principles and recommendations for the development of health information privacy and security protections that are comprehensive, transparent, understandable, adaptable, and enforceable. The principles and recommendations aim to improve on the privacy framework in which physicians have practiced for decades and expand similar privacy guardrails to entities not currently governed by privacy laws and regulations. The expanded privacy framework should protect personal health information from unauthorized, discriminatory, deceptive, or harmful uses and align with the principles of medical ethics, respect individual rights, and support the culture of trust necessary to maintain and improve care delivery.

To improve the storage and transport of clinical specimens for the diagnosis of Neisseria meningitidis (Nm) infections in resource-limited settings, we have evaluated the performance of dried blood spot (DBS) and dried cerebrospinal fluid spot (DCS) assays. DBS and DCS were prepared on filter paper from liquid specimens previously tested for Nm in the United Kingdom. Nm was detected and genogrouped by real-time PCR performed on crude genomic DNA extracted from the DBS (n = 226) and DCS (n = 226) specimens. Targeted whole-genome sequencing was performed on a subset of specimens, DBS (n = 4) and DCS (n = 6). The overall agreement between the analysis of liquid and dried specimens was (94.2%; 95% CI 90.8–96.7) for blood and (96.4%; 95% CI 93.5–98.0) for cerebrospinal fluid. Relative to liquid specimens as the reference, the DBS and DCS assays had sensitivities of (89.1%; 95% CI 82.7–93.8) and (94.2%; 95% CI 88.9–97.5), respectively, and both assays had specificities above 98%. A genogroup was identified by dried specimen analysis for 81.9% of the confirmed meningococcal infections. Near full-length Nm genome sequences (>86%) were obtained for all ten specimens tested which allowed determination of the sequence type, clonal complex, presence of antimicrobial resistance and other meningococcal genotyping. Dried blood and CSF filter spot assays offer a practical alternative to liquid specimens for the molecular and genomic characterisation of invasive meningococcal diseases in low-resource settings.

This work introduces the concept of a counting-based measurement on paper analytical devices (cPADs) to improve the utilization of numerous reactions. The design of cPADs consists of two layers of paper substrates; the first layer contains a central sample zone combined with a radial surrounded by 12 detection zones that are predeposited with the various reagents, and the second layer acts as a connection channel between the sample zone and each detection zone. The solution can vertically flow from the first to the second layer and then move through the area to each subsequent detection zone. The analyte level can be evaluated by counting the number of detection zones that change color from a blank signal. Furthermore, our cPADs exhibit a capability of implementation for a broad series of reactions. Compared to the dPAD technique, some reactions that are possibly difficult to apply in such devices can be wholly enabled in our devices. The final color reaction on cPADs can apparently occur due to its identity. We applied this technique to the monitoring of carbaryl (CBR) and copper ions (Cu

In this study, we developed a rotatable paper device integrating loop-mediated isothermal amplification (RT-LAMP) and a novel naked-eye readout of the RT-LAMP results using a food additive, carmoisine, for infectious pathogen detection. Hydroxyl radicals created from the reaction between CuSO4 and H2O2 were used to decolor carmoisine, which is originally red. The decolorization of carmoisine can be interrupted in the presence of DNA amplicons produced by the RT-LAMP reaction due to how DNA competitively reacts with the hydroxyl radicals to maintain the red color of the solution. In the absence of the target DNA, carmoisine is decolored, owing to its reaction with hydroxyl radicals; thus, positive and negative samples can be easily differentiated based on the color change of the solution. A rotatable paper device was fabricated to integrate the RT-LAMP reaction with carmoisine-based colorimetric detection. The rotatable paper device was successfully used to detect SARS-CoV-2 and SARS-CoV within 70 min using the naked eye. Enterococcus faecium spiked in milk was detected using the rotatable paper device. The detection limits for the SARS-CoV-2 and SARS-CoV targets were both 103 copies/µL. The rotatable paper device provides a portable and low-cost tool for detecting infectious pathogens in a resource-limited environment.

Two novel methods of measuring the dimensions of oral lesions are described, which would be of help in deciding relative efficacies of different therapeutic agents when used in clinical trials after larger studies quantitatively assessed for inter/intraobserver variability.

Osteoporosis and associated fractures present a major challenge in improving global health outcomes. Key clinical aspects are the definition of osteoporosis and associated fractures, fracture risk prediction, stratification of risk of fracture, intervention thresholds and the most appropriate intervention based on integration of aforementioned. Correct understanding and application of these concepts are essential to stem the increasing tide of fragility fractures associated with an aging population. The role of muscle strength and function, sarcopenia, and the newly emerging concept of osteosarcopenia in maintaining bone health are discussed in detail.

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging.

Atherosclerosis often affects the coronary arterial tree. Frequently the disease does not translate in significant narrowing of the vessels, thus determining only a non-obstructive disease. This condition that is described as non-obstructive coronary artery disease (NobsCAD) should be distinguished from the absence of disease (i.e. smooth coronary arteries) as it carries a specific prognostic value. The detection and reporting of NobsCAD should prompt preventive measures that can be individualized upon the degree of the underlying burden of disease. The accompanying clinical condition, the other cardiovascular risk factors present, and the description of the severity and extent of NobsCAD should provide the framework for an individualized treatment that should also consider the best available scientific evidence and guidelines. The description of NobsCAD represents important information to be collected whenever a coronary angiogram (both invasive and non-invasive) is performed. Treating the patient according to the presence and extent of NobsCAD offers prognostic benefits well beyond those offered by considering only the traditional cardiovascular risk factors. In order to reach this goal, NobsCAD should not be confused with the absence of coronary atherosclerosis or even ignored when detected as if it was a trivial information to provide.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings (IFs) with a series of publications entitled "Incidental Imaging Findings-The Role of Medical Ultrasound." IFs are less commonly encountered in the spleen than in many other abdominal organs but remain a frequent dilemma in clinical practice. A histological diagnosis is rarely necessary for patient management. Many IFs, such as secondary spleens and splenic cysts, are harmless and do not require any further investigation. The diagnosis of many other focal splenic lesions is, however, often problematic. The following overview is intended to illustrate a variety of incidentally detected spleen pathologies such as size variants, shape variants, secondary spleens, focal splenic lesions and splenic calcifications. It should aid the examiner in establishing the diagnosis. Moreover, it should help the ultrasound practitioner decide which pathologies need no further investigation, those requiring interval imaging and cases in which immediate further diagnostic procedures are required.

Background Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. Aims The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. Methods A panel of experts of the Italian Society of Alcohology (SIA) met via “conference calls” during the lockdown period to draft the SIA’s criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. Results and Conclusions The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

A point-of-care (POC) device is reported for highly sensitive and selective detection of Plasmodium falciparum lactate dehydrogenase (Pf-LDH), a biomarker of malaria infection, based on a single-step magneto-immunoassay, a single-use microfluidic paper device and a customized hand-held fluorescence reader. The single-step magneto-immunoassay consists in a single 5-min incubation of immuno-modified magnetic particles (c-MAb-MPs), biotinylated detection antibody (bd-MAb), and an enzymatic signal amplifier (Poly-HRP). After on-chip MP concentration and washing, signal generation is achieved by adding a fluorescent enzymatic substrate (QuantaRed). Fluorescence signal is measured using a low-cost customized, portable, and sensible fluorescent detector. The POC affords quantitative Pf-LDH detection in, This work was supported by Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (grants CPII18/00025, IFI18/00020 and QUPID EuroNanoMed AC21_2/00021). KAA is supported by an InPHINIT fellowship from “La Caixa” Foundation (LCF/BQ/DI18/11660061). ASM is supported by a Juan Rodés postdoctoral fellowship from ISCIII (JR18/00022). Diagnostic Nanotools is an AGAUR Consolidated Group (2017 SGR 240).