The COVID-19 pandemic has created enormous global demand for personal protective equipment (PPE). Face shields are an important component of PPE for front-line workers in the context of the COVID-19 pandemic, providing protection of the face from splashes and sprays of virus-containing fluids. Existing face shield designs and manufacturing procedures may not allow for production and distribution of face shields in sufficient volume to meet global demand, particularly in Low and Middle-Income countries. This paper presents a simple, fast, and cost-effective curved-crease origami technique for transforming flat sheets of flexible plastic material into face shields for infection control. It is further shown that the design could be produced using a variety of manufacturing methods, ranging from manual techniques to high-volume die-cutting and creasing. This demonstrates the potential for the design to be applied in a variety of contexts depending on available materials, manufacturing capabilities and labour. An easily implemented and flexible physical-digital parametric design methodology for rapidly exploring and refining variations on the design is presented, potentially allowing others to adapt the design to accommodate a wide range of ergonomic and protection requirements. The COVID-19 pandemic has created unprecedented global demand for large quantities of Personal Protective Equipment (PPE). Face shields have been identified as an important component of PPE for frontline healthcare workers. They are classed as “adjunctive PPE”, intended to be worn in addition to respiratory protection to provide additional protection of the facial area from splashes and sprays of bodily fluids from infected patients, specifically to the mucous membranes of the eyes, nose, and mouth .Using the WHO COVID-19 Essential Supplies Forecasting Tool (ESFT) version 3) [ [3], theThe ESFT only models the demand for face shields in critical medical and front-line applications, yet face shields are also increasingly seen as desirable in non-medical settings as a means of infection control among the general population . Some aiFailures to provide sufficient face shields to those who need them have apparently been primarily due to limitations in manufacturing and distribution capacity. In the context of the COVID-19 pandemic, shortfalls in PPE provision are likely to be further exacerbated by disruptions to global manufacturing supply chains and distribution. These may be caused by transportation restrictions, social distancing measures, or worker illness, all of which can potentially lead to labour and material shortages and reduced manufacturing productivity, adversely impacting the timely production and distribution of essential PPE. Face shield shortfalls are likely to be especially high in less wealthy countries, which are often unable to compete with wealthier countries on a price basis to import PPE during a global shortage . ScalingThe provision of sufficient face shields is also hindered by the potentially diverse ergonomic, performance, and protection requirements of users. Some medical use-cases for face shields require that additional medical devices, such as surgical loupes, be worn underneath face shields, potentially requiring an adapted design suited specifically for this application. Furthermore, if the general population is increasingly required to wear face shields, designs which provide sufficient protection and comfortable fit for a variety of wearer headforms, including children, are required. Developing and testing novel face shield designs suited to different users and applications is technically challenging and time-consuming, potentially reducing the speed and volume at which face shields can be delivered to these populations.In addition to variation in user requirements, differences in availability of raw materials, manufacturing equipment, and skilled labour in various regions may limit the ability of manufacturers to scale production of an existing face shield designs, a challenge already highlighted as impacting less wealthy countries especially severely. The growing Free and Open-Source Hardware (FOSH) movement may provide lessons in rapid, collaborative, distributed design, testing, and manufacturing of PPE in response to the COVID-19 pandemic in a diverse range of contexts [Many existing face shield designs are intended to be single-use, largely due to the challenges with ensuring efficient and effective decontamination. Given the enormous global demand for face shields projected over the course of the pandemic, high volumes of plastic waste, contained in clinical waste streams, are likely to enter landfills as a result. Assuming 50 grams of plastic are used for one single-use face shield, the consumption of 1.03 billion face shields over the coming 12 weeks could result in 52 kilotonnes of plastic waste entering landfill.New designs and manufacturing methods for face shields which are cost-effective, allow for rapid high-volume production, and are resilient with respect to supply chain disruptions could allow for increased production of face shields to meet predicted global demand. Challenges in local production of face shields in low-income regions could be addressed through the development of face shield designs which may be manufactured using a variety of available manufacturing methods, materials, and labour. Simple designs which may be replicated and adapted easily with minimal specialist knowledge could allow for manufacturers in both wealthy and low-income countries to modify the design to best suit the performance and ergonomic requirements of their intended user. Challenges in rapid global distribution, particularly to rural and remote areas, could be addressed through designs which may be transported in a space-efficient manner.Designs which allow face shields to be safely reused could also significantly reduce global demand for face shields, reduce plastic waste, and result in significant cost savings. Assuming they could be safely reused over 10-50 shifts at equivalent cost and material consumption, reuseable face shields could reduce demand by 90-98%, resulting in global PPE cost savings of approximately $560-610 million, and the prevention of approximately 47-51 kilotonnes of plastic from entering landfill over the coming 12 week period. Reuse could also help to ensure sufficient supply of face shields during interruptions to manufacturing and distribution which, if only single-use face shields were available, would result in shortages or require significantly higher stockpiling of face shields to prepare for. Challenges in reusability of face shields could be addressed through designs which minimise the use of materials which are difficult to decontaminate, are designed with geometries that result in minimal trapping of soiling and maximal access by decontaminating agents, and are easy to visually inspect for soiling.This paper presents a design  for a faThe function of face shields for infection control is to protect the wearer from liquid droplets and sprays which may contain infectious agents. Face shields must also allow other PPE, including respiratory protection  and additional eye protection (such as goggles) to be worn in conjunction with the face shield. Specific design and performance requirements for face shields for infection control vary by jurisdiction.The performance requirements for face shields for a variety of applications are described in European standard EN 166. The face shield design presented in this paper was tested to the British Standards Institute’s PPE Technical Specification 2020/403 for Healthcare Professionals during the COVID-19 Pandemic, which cites performance requirements outlined in EN 166, listed below:BS EN 166:2002: 6.1. General ConstructionBS EN 166:2002: 6.2. MaterialsBS EN 166:2002: 6.3. HeadbandsBS EN 166:2002: 7.1.1. Field Of VisionBS EN 166:2002: 7.1.2.2. Spherical / Astigmatic / Prismatic / Refractive PowersBS EN 166:2002: 7.1.3. Quality of Material And SurfaceBS EN 166:2002: 7.2.4. Protection Against Droplets and Splashed of LiquidsBS EN 166:2002: 7.2.8. Lateral ProtectionThe key requirement of face shields as described in EN 166:2002: 7.2.4. Protection Against Droplets and Splashes of Liquids, is the protection of the mucous membranes of the eyes from direct contact with liquids and sprays containing infectious agents.Due to the severe shortages of PPE experienced during the COVID-19 pandemic, revised recommendations have been made by a number of public health bodies concerning the use of PPE. The WHO, in particular, recommends the following “last resort temporary measures”, which may be “considered independently or in combination, depending on the local situation” when severe PPE shortages are likely to be experienced :PPE extended use ;Reprocessing followed by reuse (after cleaning or decontamination/sterilization) of either reusable or disposable PPE;Considering alternative items compared with the standards recommended by WHO.The above recommendations have a number of implications for the purpose of the development of new face shield designs which may be used in contexts experiencing severe PPE shortages. The recommendation that PPE be worn for longer periods increases the importance a comfortable fit for as wide a variety of wearer physiologies as possible, and the minimisation of excessive pressure, chafing, scratching or other sources of discomfort or potential injury which may result from wearing face shields for extended periods. The recommendation that reprocessing of face shields be considered necessitates face shield designs which may be effectively decontaminated, ideally in a labour and resource-efficient manner.Since the beginning of the COVID-19 pandemic, a variety of organisations and institutions have developed novel face shield designs and production methods. Based on a survey of these designs, four broad categories of face shields were identified. These categories are distinguished largely by the design, manufacturing procedure, and materials used in the face shield suspension system, which supports the transparent visor that provides the primary protective function. It was observed that while suspension systems varied widely, visor components were largely similar between designs, typically consisting of an elastically bent sheet of flexible clear plastic.The categories of face shields identified were the following: face shields which use a 1) foam pad, 2) rigid plastic frame, 3) flexible plastic band, or 4) contiguous folding of the visor sheet for their suspension systems, as shown in The first category of face shields surveyed are those incorporating foam strips and an elastic headband as a means of supporting the visor in front of the face in a curved configuration. Manufacturing procedures described for these designs typically make use of manual assembly processes, resulting in reported production capacities of 1500 face shields per day at one institution .While the use of a foam pad likely helps to provide a comfortable fit for a variety of wearer headforms, it has a number of disadvantages with regards to the face shield provision in the context of the COVID-19 pandemic. First, effective decontamination and visual inspection of soiling is likely to be more challenging in face designs incorporating foam pads. Porous open-cell foam material may trap infectious agents both inside the material, and at the interfaces of the material and the visor. Both of these locations are difficult to visually inspect. A preliminary study of decontamination of face shields incorporating foam in the headband region found that biological indicators placed in the foam were not successfully sterilised . DecontaFurthermore, the relatively high number of unique materials required in some surveyed designs using a foam pad  increases the sensitivity of production of such designs to supply chain disruptions caused by the pandemic. Finally, the inclusion of foam pads limits the distribution efficiency of face shields by increasing both their volume and potentially the volume wasted in packing for storage and transport. The worst-case packing thickness of such designs, equal to the combined thickness of the foam pad and the visor sheet material, is likely to be approximately 20-25 mm, which is significantly higher than other designs surveyed.A large number of the surveyed face shield designs used rigid plastic elements as a frame for supporting the visor and enforcing the desired surface curvature. In some instances, these plastic elements were manufactured using 3D printing technology. While 3D printing allows for straightforward reproduction of designs with low barriers to entry in manufacturing procedure set-up, it suffers from very slow manufacturing times. Reported fabrication rates of designs produced using 3D printing methods reached 1,000 face shields per week (approximately 150 per day), depending on the scale of the production facility . FurtherA third category of face shields are designs where some or all of the headband component is cut from the same transparent plastic sheet material as used for the visor. This allows for high-volume and straightforward manufacture using laser-cutting or die-cutting methods. Die-cutting manufacture allows for the highest production rate of face shields reported, at up to 90,000 shields per day at one facility . SmallerFinally, a small number of designs , 30, 31 The designs presented in , 30, 31 The design presented in this paper , shared The above survey of existing face shield designs highlighted large differences in the production rates of face shields resulting from the use of certain manufacturing processes, ranging over nearly three orders of magnitude. The survey also highlighted the importance of material selection to enable effective decontamination of face shields for reuse. The inclusion of open-cell foams, 3D printed materials, and adhesives was identified as potentially preventing effective decontamination.To illustrate the importance of high-volume production and the ability to effectively reuse face shields, it is worth considering the rate of production required to meet global predicted demand for face shields in the single-use and reuse cases. Assuming a production rate of 90,000 face shields per day from a known die-cutting facility   through to computer-controlled cutting methods  and a variety of pressing methods (die-cutting and stamping). This flexibility with respect to manufacturing methods is a key advantage in the context of the provision of PPE during the COVID-19 pandemic, where distributed manufacturing approaches making use of locally available machinery and labour could help to meet PPE demand in developing and remote regions.When combined with folding, in an “origami” approach, sheet material manufacturing techniques may be used to produce complex, varied, and high-performance mechanisms and structures. Diverse available folding patterns can achieve a variety of functionalities, such as deployability, load-carrying capacity, and kinetic energy dissipation behaviour. Origami folding techniques have been increasingly studied and adopted across a wide range of disciplines, including medicine, aerospace, and architecture.Curved-crease origami are a class of origami structures that possess curved fold lines, rather than the straight fold lines seen in typical origami. Curved-crease origami allow transformation of flat sheet materials into complex three-dimensional forms which possess curved surface regions, as their unique curved folds cause bending in the sheet material during the folding process , 34.Recent research has demonstrated concise analytical models for designing the three-dimensional surface geometries of certain special cases of curved-crease origami . These cThe face shield design presented in this paper  uses an Rather than a permanently affixed headband strap as in , the desSubject to validation of an effective decontamination procedure, the shield design could potentially be decontaminated for reuse by removing the headband, flattening the shield, and decontaminating the shield surface using a variety of cleaning and sterilising methods. The shield, apart from the removable, disposable headband, contains no materials or components  or geometric features likely able to trap infectious agents or limit access of sterilising agents. Finally, the design requires only two materials (PET sheet and elastic strapping), resulting in minimal supply chain sensitivity. This design was developed using an iterative two-stage procedure involving both physical prototyping and digital refinement and visualisation , describPhysical prototyping of the face shield design presented in this paper used manual cutting, creasing, and folding methods to rapidly produce prototypes for evaluation. This procedure was used to determine the approximate geometry of the boundary curve, folding curves, and the location and dimensions of the strap attachment holes of the face shield. This process, through which novel face shield geometries could be manufactured and evaluated within five to ten minutes, allowed for rapid evolution of the design to meet key performance requirements. Physical prototyping was conducted first using cardboard, later using 440 micron acetate plastic sheeting, and finally using 510 micron polyethylene terephthalate (PET) sheets.Physical prototyping was first used to determine the approximate location of the two curved foldlines in the face shield design. The position and shape of the foldlines affect the fit, protection, and mechanical behaviour of the face shield. A key consideration of the design is the angle between the forehead rest portion and front visor portion of the shield, which arises from the relative orientation of the two foldline reflection planes in an assumed elastica surface curved crease origami rationalisation of the face shield design. Experimentation through physical prototyping determined that in order to allow the forehead rest to adapt comfortably to the sloping profile of the human forehead, while orienting the front visor such that it did not project too far out from the face, a deviation angle of approximately 30 degrees between the forehead rest and front visor was effective.A second key consideration for the design is the position of the front visor with respect to the face. The front visor must be far enough from the face to allow primary PPE  to be worn comfortably underneath the face shield, but not so far away from the face that protection from splashes and droplets is compromised. During physical prototyping it was also observed that the distance of the face shield from the face also influenced the likelihood of fogging, caused when water vapor suspended in exhaled gases condenses onto the inside of the front visor. Fogging increased when the front visor was closer to the face likely due to the reduced ability for vapor to leave the volume between the wearers face and the front visor, prior to condensation occurring. The distance of the front visor from the wearer’s face is controlled largely by the distance between the two folding curves.The design of the boundary cutting curves for the face shield was informed by protection and performance requirements, including that face shields: provide adequate lateral protection from droplets and splashes; not restrict movement of the head with respect to contact with the shoulders and chest; and have no sharp projections which could pose a scratching or cutting hazard, particularly during donning and doffing. Physical prototyping and preliminary testing of shield samples to EN 166 requirements informed the width and height of the sheet used for the face shield. To reduce the sharpness of the shield geometry at locations which could pose a scratching or cutting risk, the upper corners of the shield were filleted along a circular profile, a geometry chosen for ease of replicability using non-digital fabrication methods. The bottom corners of the shield design follow a freeform curve chosen to balance protection and freedom of movement requirements. The boundary geometry also influenced fogging behaviour, with larger shields, particularly those with significant extension of the front visor below the chin, resulting in greater fogging.The location and dimensions of the strap attachment holes was found to significantly influence the geometry of the face shield when worn. Physical prototyping determined that higher strap attachment hole locations caused the front visor surface to spread laterally, assuming a more flat curvature towards the bottom of the shield. Lower strap locations resulted in the face shield geometry assuming a tighter surface curvature, particularly towards the bottom of the shield.The aim of the physical prototyping procedure described in the above sections was to produce an approximation of the final geometry of the boundary curve, folding curves, and strap attachment hole locations and dimensions which were likely to result in designs satisfying all performance requirements. The folding curves produced using manual fabrication methods were intended to correspond approximately to those created using an elastica curved-crease origami surface generation approach. This section describes a procedure whereby a digital parametric model incorporating elastica surface generation was used to generate refined digitised folding curves based on those generated using manual methods.The face shield was modelled using a three-dimensional parametric analytical model of a twice-mirrored extruded elastica shell . This paL: Horizontal sheet length.w: Vertical sheet length.b: Distance between the side edges of the face shield in its worn configuration, equal to the width of the wearer’s head at this point plus a gap.θa: Inclination angle of Mirror Plane A, where Mirror Plane A intersects with the top corners of the sheet.wb: Distance of Mirror Plane B from the top of the sheet.θb: Inclination angle of Mirror Plane B.L and b describe a unique elastica, corresponding to the arc length and distance, respectively, between the elastica’s end supports. In this study, elastica curves were generated in a Rhino-Grasshopper parametric CAD environment using an open-source numerical solver [w , and mirrored at Mirror Planes A and B, this elastica provides a prediction of the three-dimensional surface geometry of the face shield. Boundary curves and strap attachment holes are assumed to be cut from this surface without altering its curvature. Importantly, this elastica surface generation approach assumes continuous translational restraint along the two edges in the extrusion axis .As implemented in the Rhino-Grasshopper environment, this parametric geometry modelling tool is able to generate 3D geometry visualisations with sub-second response times on a typical personal computer, allowing for effectively real-time exploration of design options. The geometry generated using this digital refinement procedure was subsequently used to manufacture the face shield using digitally-enabled fabrication methods. Multiple iterations of manual physical prototyping, digital refinement, and digital fabrication were used to refine and generate the final design presented in this paper.To evaluate the usefulness of the analytical mirrored elastica curved-crease origami approach for prediction of the geometry of the face shield, a 3D scan using photogrammetry was performed of a face shield on a wearer’s head . 120 phoThe deviation of the 3D scan mesh from the analytically predicted geometry was measured by comparing the scan mesh with the surface prediction at 11 extraction points on the generated surface, indicated as blue spheres in The distance between the between the 3D scan mesh and predicted geometry at all extraction points except for the top corners and top of the forehead rest was less than approximately 2.5 mm (approximately 5 times the thickness of the PET sheet). At the top right and left corners of the face shield, deviations between the 3D scan and the predicted geometry were greater, at approximately 15 and 11 mm, respectively. At the extreme point selected at the top of the forehead rest a deviation of approximately 14 mm was measured.The above results demonstrate that the analytical prediction corresponds reasonably well to the true geometry of the face shield as measured using the 3D scanning method employed. The differences between the actual face shield and the analytical prediction are primarily due to the differences in support conditions in the analytical model compared to the actual face shield, as discussed in the previous section. The analytical shape prediction was also simplified to assume a rectangular boundary and no internal cuts, both of which would alter panel bending stiffness in the physical face shield.The reasonably good correspondence between the analytical prediction of the geometry of the face shield and its true geometry as measured with a 3D scan suggest that the parametric modelling approach used to predict and visualise the geometry of the face shield is likely to be useful in the design process of future iterations and adaptions of this face shield. It is important to note here that several rounds of iterative prototyping may be required to determine strap attachment locations which result in minimal change in surface curvature of the front visor along its height, thus ensuring closest agreement with the analytically predicted geometry. A further factor which was found to potentially influence the geometry of the face shield when worn was the orientation of the sheet material in the face shield with respect to its rolling direction when packed for transport. The 510 micron PET sheet used in this study exhibited some residual curvature due to plastic deformation from being rolled. This could potentially influence the geometry of the face shield if the rolling direction during storage and transport coincides with the bending direction in the face shield’s worn configuration.The above approach using both physical prototyping and parametric digital design refinement may be used to rapidly explore and refine further iterations on the design presented in this paper. In particular, using the above approach, designers may straightforwardly adapt the design to different wearer head-forms, or make alterations to the geometry as needed to accommodate specific protection, ergonomic, comfort, or other requirements.wb by 35 mm, to increase the extension of the top visor, thereby moving the front visor forward. As this also translates the front visor up, the vertical length of the shield w was increased by 55 mm to retain the same protective coverage around the chin. All other parameters remained unchanged. L of the sheet, and the target edge-to-edge width of the shield in worn configuration b were reduced to accommodate the smaller width and circumference of the child headform. The height w of the shield was also reduced to eliminate excessive extension of the bottom of the shield below the child’s chin. All other parameters remained unchanged. These alternative design variants have not been tested or certified, but are shown to demonstrate the adaptability and potential utility of the design process presented in this study. These designs are not intended to be representative of face shields required for all populations but rather illustrate potential modified designs suitable for specific populations potentially not well served by the “Original” face shield design presented in this paper.L, which may be reduced to correspond to the reduced circumference of smaller wearer headforms, the vertical sheet length w, which controls the downward extension of the front visor, and the parameter wb, which controls the size of the top visor, which could be used to vary the distance of the front visor from the wearer’s face as needed. The parameter b, corresponding to width of the wearer’s head plus a gap, should also be adjusted accordingly for smaller or larger wearer headforms to enable accurate geometry prediction using the analytically generated face shield surface.Generally, the key parameters which may be adjusted to adapt the geometry of the face shield to diverse wearer headforms are likely to be the horizontal sheet length A key objective of this work was the development of a design which could be produced using a variety of manufacturing methods, and a range of plastic sheet materials, to enable the rapid scaling of global production in the disrupted COVID-19 manufacturing and supply chain environment. A number of manufacturing procedures . The specific selection of the type of thermoplastic for use in face shields is further based on properties such as mechanical behaviour, optical quality, chemical resistance, and impact and scratch resistance. A wide range of thermoplastics have been utilised in recent face shield designs, including polycarbonate , celluloThe design and fabrication methods presented in this paper were tested using transparent sheets of 440 micron cellulose acetate and 510 micron PET. Prototyping was also briefly conducted using 250 micron PET, however this material failed easily in a brittle manner near strap attachment holes, and was therefore not used further. Further work should explore the manufacture of these face shields using other thermoplastic sheet materials.During initial physical prototyping, the cutting of boundary curves in plastic sheets was performed using scissors, and the cutting of strap attachment holes was performed using a utility knife. Strap attachment holes were also in some instances produced using manual hole punchers. To produce consistent and accurate cuts, tracing was used to transfer the geometry of the boundary curves and strap attachment holes to the plastic sheet. An individual shield could be cut manually in approximately 1-3 minutes. These methods, while slower and less accurate than mechanised methods, produced shields of acceptable quality for use. Specifically, manual cutting of the boundary curve was found to approximate the desired target geometry well enough so as to not affect coverage performance. However, care should be taken with manual cutting of the boundary curve so as not to introduce sharp projections (which could pose a scratching hazard) or slits , and could be completed in conjunction with complete depth cuts required for boundary curves and strap attachment holes. A key disadvantage of this approach, however, is the creation of a channel which may trap soiling material, and prevent effective decontamination of the face shield for reuse. A further challenge observed with such incomplete depth cuts when prototyped was a higher incidence of brittle failure at or near the creases when folded. Our hypothesis is that the very small radius of curvature of the folding hinge created at this type of crease results in high localised stress concentrations, increasing the risk of a brittle failure. A further challenge with the above approach may be controlling the precise depth of the partial depth cut using a laser cutter, particularly when the sheet material may not rest completely flat on the laser cutting bed, or when precise laser power and speed settings may be difficult to reliably control.A further creasing method explored as part of this work was the use of complete depth cuts along the desired folding curve which do not completely join (for example “dashed” cuts), leaving sheet material in place at least in some locations across the creasing curve. A large body of literature has explored complete depth cut patterns for the creation of hinges in sheet materials –44.While such a creasing approach would benefit from straightforward manufacture using a laser-cutter (at an estimated 30-90 seconds per shield) or potentially high-volume die-cutting, a key disadvantage of such creases is their permeability to fluids and aerosols. Furthermore, the gaps produced by such cuts could trap soiling material, and prevent effective decontamination for reuse. This work also explored the use of a flexible transparent fluid-repellent adhesive-backed sheet (contact paper) applied over complete depth cuts as a means of providing a fluid and aerosol barrier there. While such a method could help to provide protection from fluids and aerosols in designs using complete-depth cut creases, the robustness of such a laminated hinge when subject to multiple rounds of repeated folding and unfolding, in addition to decontamination involving liquid and manual abrasion, could be poor, potentially resulting in loss of protective function after a small number of reuses.For all of the shields produced as part of this study, sheets were manually folded along creases. This folding procedure typically took between 30 and 90 seconds per shield, depending on desired fidelity of the fold beyond that required to satisfy performance requirements.It should be noted that it is possible for users to potentially produce low quality shields when manually folding, if folds are made away from the creases . When folded with reasonable care, however, excellent fold robustness and consistent worn geometry are achievable. This experience suggests that folding could be performed by first-time users of face shields upon opening of shield packaging, thus allowing for space-efficient transportation of shields in their flat-packed configuration.Strap attachment clip folding, threading, and attachment to visors for all shields produced as part of this study was performed manually. Threaded straps could be shipped attached to flat face shields, resulting in worst-case packing thicknesses of approximately 5.0 mm, or unthreaded, requiring that users thread and attach these upon opening shield packaging, resulting in worst-case packing thicknesses approaching sheet material thickness at 0.5-1.0 mm. Strap threading and attachment could be performed in 1-3 minutes per shield. Apart from easily avoidable errors in threading pattern, strap attachment orientation, and tightness, high quality strap threading and attachment may easily be achieved by first-time users when provided with instructions.It is of interest to identify which of the manufacturing methods discussed above are compatible with each other, so that producers of face shields may make best use of the manufacturing methods available to them. Manual cutting methods are generally likely to be incompatible with mechanised creasing methods, because such mechanised methods are likely to require precise boundary curves for registration, which may be difficult to achieve using some manual cutting methods. Laser and die-cutting methods are likely to be compatible with any creasing method. All methods considered are compatible with manual folding and strap threading and attachment, the only folding and strap attachment methods considered in this paper. Both PET and acetate are potentially compatible with all methods, however, as previously mentioned, brittle failures were observed in thin (250 micron) PET when produced using laser cutting and mechanical pressure creasing. Those manufacturing curved crease origami face shields are responsible for testing these according to medical device performance standards in their jurisdiction to ensure that the particular manufacturing methods and materials used in their production result in face shields which are fit for purpose.A version of the face shield design presented in this paper (denoted model number HS-00-00-01) passed all of the tests described in the BSI’s PPE Technical Specification 2020/403 for Healthcare Professionals during the COVID-19 Pandemic, as tested on the adult reference head-form for eye protection evaluation described in EN 166, clause 17. The design tested used 510 micron PET, laser cutting, mechanical pressure creasing, and manual folding and strap attachment. The tests and checks performed are listed in Section 2.1.This testing was part of the conformity assessment  process required for permission from the United Kingdom Office for Product Safety and Standards to manufacture and distribute face shields for infection control during the COVID-19 pandemic. This process, which also involved a review of technical documentation and proposed manufacturing procedures, was granted for the manufacturing of this face shield design at the University of Cambridge Department of Architecture. This approval means that, according to UK public health guidance and European Standards, the design was deemed fit for purpose as a face shield for infection control during the COVID-19 pandemic, and subject to controlled manufacturing procedures, could be distributed as a face shield for infection control within the UK. It is important to note that this approval applies only to shields manufactured by University of Cambridge Department of Architecture using the materials and manufacturing methods associated with the shields which were tested as part of the approval process.Preliminary feedback regarding shield designs was also obtained from a small number of healthcare workers. Comments focussed on the fit, comfort, degree of fogging, and overall size of the shields. Users reported that the shields were comfortable to wear for extended periods, and fogging was not reported as a concern. In hot conditions, sweating in the forehead rest region was identified as a potential issue, but was ultimately not found to be a significant concern. Early feedback from users also informed the design of the front visor, whose size in later design iterations was limited to prevent restriction of head movement.A comprehensive study involving human participants to evaluate the performance of the face shield was outside of the scope of this work, and not required for CE certification. As this work did not involve randomising participants to different groups, did not involve any change to treatment or standards of care, and was not intended to provide generalisable research findings, it was deemed to fall outside the the scope of research as considered by the UK National Health Service (NHS) Health Research Authority  and no fIt is also important to note that, although preliminary user feedback did not report fogging as a concern, some design variants tested by the authors did exhibit some fogging. Increasing the space between the front visor and the wearer’s face and limiting excessive extension of the bottom of the front visor were identified as potential strategies to mitigate fogging if this appears to be a concern in future design variants. The above-mentioned BSI testing procedure for CE approval face shields for infection control in the COVID-19 pandemic did not include any tests for fogging.Further tests were conducted to assess the likelihood of the ability for the face shield presented in this paper to be safely reused. A preliminary evaluation of a potential decontamination procedure was conducted, whereby the strap was removed from the shield, the shield was flattened, and liquid soap was used to manually clean and disinfect the shield. Once dry, sterilising wipes containing chlorhexidine were used to sterilise the shield. Disinfection using sterilising wipes has been suggested in United States Centers for Disease Control and Prevention (US CDC) guidance  and in rSubject to the development of an acceptable decontamination procedure for these, straps and clips could also be decontaminated and reused. Collaborative work by the authors has explored variants of the design presented in this paper which incorporate a headband consisting of a plastic strap of the same sheet material, possibly contiguous with the face shield sheet, which could be easily decontaminated alongside the face shield using the procedure described above, eliminating any face shield material waste as a result of decontamination.b of 210±20 millimetres in its three-dimensional configuration.To assess the mechanical performance of the face shield subject to multiple reuses, a preliminary fatigue test was performed. The fatigue performance of a face shield using 510 micron PET, produced using laser cutting, mechanised pressure creasing, and manual strap attachment and folding was assessed. In this experiment, the face shield, with its strap removed, was folded from its three-dimensional configuration to its flat configuration repeatedly to assess the mechanical effects of repeated folding and unfolding, as would occur over multiple decontamination cycles. The shield was flattened and unflattened manually, and a distributed weight was applied over the entire shield surface to improve consistency of flatness with each cycle. To ensure consistency of folding into the three-dimensional configuration, the shield was folded to a target edge-to-edge distance No visually discernible damage to the creases occurred over 100 fold cycles, and no cracks in the shield were observed, meaning that fluid-impermeable barrier function of the shield was not compromised. A slight apparent reduction in folding stiffness was perceived after 5-10 fold cycles. These preliminary results suggest that mechanical failure is unlikely to occur in curved crease origami face shields using the materials and manufacturing methods tested, for a relatively high number of estimated reuses.It should be noted that preliminary experiments on various materials and creasing methods throughout the prototyping process suggested a strong influence of material choice and creasing technique on the number of fold cycles before failure, and thus those adapting this design should ensure that the materials and creasing methods selected provide the desired crease robustness for the intended application. The effect of disinfecting agents on the optical and mechanical characteristics of the face shields was not evaluated.This paper has identified the potential for curved-crease origami techniques to be used to efficiently produce large volumes of face shields for infection control using a wide range of manufacturing methods as appropriate to specific contexts.Through an analysis of the state of the art in face shield design, this paper has highlighted the importance of rapid high-volume manufacture, the ability to be safely reused, resilience against disruptions to supply chain, manufacturing, and labour, and ease of replication and adaptation in the design of face shields for infection control. The design presented may be manufactured at high production rates, transported and stored efficiently. Subject to the validation of an approved decontamination procedure, the design could potentially be easily decontaminated and reused. It uses small quantities of inexpensive raw materials, requires only two unique materials and is likely to be easily produced using alternative raw materials. The design also has a simple geometry which may be easily replicated and adapted using manual or widely available digital fabrication methods.In addition to reporting on the specific design developed in this work, this paper has also detailed the iterative physical-digital prototyping procedure used to develop the design, which may be used by others to further improve and adapt the design to new contexts and applications. The elastica curved crease parametric modelling approach presented allows for the rapid and accurate visualisation of predicted final forms of face shields in their worn configuration as determined by a small number of input parameters which may be controlled by the designer. This design and visualisation tool, implemented in Rhinoceros CAD software using the Grasshopper parametric modelling environment is available open-source in the supplemental data associated with this paper. Equivalent tools could easily be implemented in other software as needed, using the method described in this paper.Beyond their application specifically for face shields, the explorations conducted in this study have highlighted the potential for curved-crease origami techniques to be applied in the design of other PPE and wearable devices. Curved-crease origami forms consist of curved surfaces which may conform well to human body forms, providing flexible contact regions which distribute attachment forces across a large area, reducing pressure which might otherwise cause discomfort or even soft-tissue injury. Wearables may also benefit from the compliant mechanism behaviour of curved-crease origami forms, as in the case of the face shield design presented, whereby the process of donning the shield reconfigures the shield from its flat to its three-dimensional form. Furthermore, as with other origami techniques, curved-crease origami allows for cost-effective and straightforward manufacture from sheet materials.The severity and urgency of the COVID-19 pandemic have resulted in remarkable innovations from the design community, revealing extraordinary opportunities for improvements in the quality, efficiency, and sustainability of provision of critical goods and services globally, particularly to the most vulnerable. We are encouraged by the potential for further focused, collaborative, and open-source design in the field of folded structures to help address the numerous challenges facing humanity now and in the future.


Neuropathic pain is difficult to cure and is often accompanied by emotional and psychological changes. Exploring the mechanisms underlying neuropathic pain will help to identify a better treatment for this condition. The insular cortex is an important information integration center. Numerous imaging studies have documented increased activity of the insular cortex in the presence of neuropathic pain; however, the specific role of this region remains controversial. Early studies suggested that the insular lobe is mainly involved in the processing of the emotional motivation dimension of pain. However, increasing evidence suggests that the role of the insular cortex is more complex and may even be related to the neural plasticity, cognitive evaluation, and psychosocial aspects of neuropathic pain. These effects contribute not only to the development of neuropathic pain, but also to its comorbidity with neuropsychiatric diseases. In this review, we summarize the changes that occur in the insular cortex in the presence of neuropathic pain and analgesia, as well as the molecular mechanisms that may underlie these conditions. We also discuss potential sex-based differences in these processes. Further exploration of the involvement of the insular lobe will contribute to the development of new pharmacotherapy and psychotherapy treatments for neuropathic pain. Neuropathic pain occurs when the somatosensory nervous system is damaged due to disease or trauma. Its main symptoms include hyperalgesia, allodynia, and spontaneous pain. Hyperalgesia and allodynia refer to increased pain perception in response to stimuli that usually do and do not cause pain, respectively . NeuropaMu-opioid receptor (MOR) agonists, such as morphine, are the gold standard of analgesia for various types of pain, such as cancer and severe acute pain . HoweverNeurosurgical inventions are also options for the treatment of neuropathic pain , such asAs the insular cortex is relatively hidden, the embedding of a cannula or an electrode in the insular lobe for laboratory animal research is difficult. Thus, the insula is more mysterious to neuroscientists than other cortical regions. The rapid development of imaging technology has enabled researchers to explore the functions of the insula. Anatomic studies have confirmed that the insula is connected with many brain structures, such as the somatosensory cortex, limbic system, and frontal lobe . ImagingSome researchers have suggested that the insula is an important information integration center  or an arThe role of the insula in neuropathic pain has been of interest for decades. The historical progress is shown in In 1999, Treede et al. proposed that the insular cortex may be involved in the affective–motivational dimensions of pain . Since 2Although many studies have found that the insular cortex is essential for pain processing, it is still difficult to explain how it participates in pain. In this review, we introduce the structural and functional changes of the insular lobe in the neuropathic pain state and the related molecular mechanisms. There are other brain regions involved in pain, such as the thalamus, primary somatosensory cortex (SI), secondary somatosensory cortex (SII), anterior cingulate cortex (ACC), and frontal cortex ,33. EachImaging studies have shown that neuropathic pain can affect the volume or thickness of the insular cortex. Gustin et al. found that the anterior insular gray matter volume (GMV) was reduced, whereas the posterior insular GMV increased in patients with trigeminal neuropathic pain (TNP) . A meta-Another study revealed thinning of the cortex of the right dorsal posterior insula and ventral anterior insula in patients with right-side trigeminal neuralgia (TN) , suggestN-acetylaspartate (NAA) concentration in the insular lobe was significantly decreased in patients with severe traumatic brain injury -fluorodeoxyglucose PET ([18F] FDG-PET) can be used to observe the changes in metabolism and can reflect the activities of brain regions. Using [18F] FDG-PET, a study found that transcranial direct current stimulation (tDCS) can relieve the neuropathic pain caused by traumatic spinal cord injury, can increase the metabolism in the insula and the ACC, and can decrease the metabolism in the dorsolateral prefrontal cortex  diprenorphine revealed reduced opioid binding in the contralateral insula in patients with post-stroke pain, but not in those with peripheral neuropathic pain [However, the opioid receptor binding ability in the insula may be weakened in certain neuropathic pain states. A PET study conducted with [hic pain . Animal hic pain . These rOpioid receptors can be divided into several subtypes. In neuropathic pain, the binding rate of the MOR is reduced, but other receptors are not affected. The DOR may be a potential analgesia target for the treatment of neuropathic pain. However, the relationship between the DOR and the insula is still unclear. The kappa-opioid receptor (KOR) in the insula is a potential analgesic target . Therefo1) receptors are distributed widely in the brain and participate in the regulation of memory, cognition, and other functions, such as analgesia. Similar to the opioid antagonist, microinjection of the CB1 antagonist AM-251 into the insular cortex can also inhibit the analgesic effect of NSAIDs in rats with inflammatory pain [1 receptor, into the insular cortex of rats with sciatic nerve ligature-induced neuropathic pain has a significant analgesic effect, which can be blocked by both KOR and CB1 antagonists [Cannabinoid (CBory pain . The injagonists .Fatty acid amide hydrolase (FAAH) is an enzyme that can hydrolyze the endogenous cannabinoid anandamide. The administration of FAAH can block the analgesic effect of anandamide . URB597 1 receptors (endogenous cannabinoid or microinjection of cannabinoid receptor agonist) in the insular lobe can produce an analgesic effect in neuropathic pain. Therefore, cannabinoid receptors in the insular lobe may be a potential target for the treatment of neuropathic pain. They may affect pain-related memory and cognition rather than pain sensation.These findings confirm that the activation of CB1 and D2, are also found in the insular cortex. Administration of the D1 receptor agonist and the D2 receptor antagonist in the rostral agranular insular cortex (RAIC) relieved neuropathic pain in rats [Dopaminergic receptors, including D in rats . The inj in rats . These fNeuropathic pain is very common in patients with Parkinson’s disease (PD) ,87,88. UN-methyl-d-aspartate receptor) in the insular cortex was found, and a microinjection of the NMDAR antagonist into the insula was shown to relieve the allodynia-like behaviors [Nerve injury-induced neural plasticity in the insular cortex may contribute to neuropathic pain, and the long-term potentiation of glutamatergic transmission may also play an important role in this process. In mice with a peripheral nerve injury, an increase in synaptic NMDAR  is an important signaling molecule involved in neuroplasticity and is often used to characterize the activation of brain regions. In rats with chronic constriction injury of the infraorbital nerve, which is a model of trigeminal neuropathic pain, moving and stroking of the infraorbital skin were shown to significantly increase pERK-1/2 expression in the insular cortex . This fiIncreased expression of pERK in the insular cortex was also observed in rats with neuropathic pain induced by SNI of the sciatic nerve . In a moRapamycin is a specific inhibitor of the mechanistic target of rapamycin (mTOR). Signaling by mTOR can influence synaptic plasticity. In recent years, significant progress has been made in the use of rapamycin to treat neuropathic pain. Animal experiments have shown that the microinjection of rapamycin into the insular cortex can reduce the neuronal activity and can inhibit the synapse plasticity induced by neuropathic surgery ,98,99. IThe mTOR signaling pathway can regulate the autophagy . StudiesThe insula is considered to be involved in pain empathy, which is the ability to perceive and understand the pain of others . In receIn rats with partial ligation of the infraorbital nerve (pl-ION) causing neuropathic pain, a local injection of oxytocin into the injured infraorbital nerve combined with local low-level laser therapy inhibited the excitation of the somatosensory cortex and insular cortex induced by dental pulp electrical stimuli . These sThere are other molecular mechanisms involved in neuropathic pain processing in the insular lobe. A study observed increased concentrations of choline in the posterior insular cortex in rats with oxaliplatin-induced neuropathic pain . As a ceNeuropathic pain has demonstrated significant sex-based differences in many studies. The prevalence of neuropathic pain, such as TN, postherpetic neuralgia (PHN), complex regional pain syndrome (CRPS), and fibromyalgia, was shown to be higher in women compared with in men ,113,114.Some studies discussed the sex dimorphism of insula structure alterations in chronic pain, including irritable bowel syndrome (IBS) , migrainThe sex difference of insula was also explored at the molecular level. A study found that the dopamine (DA) and serotonin (5-HT) levels in certain brain areas (including the insula) in female rats were higher than those in male rats. The ratios of DA metabolite/DA and 5-HT metabolism/5-HT in the insula, as well as other regions of the male brain, were also found to be higher than for female rats . This suOxytocin (OXT) plays a more important role in sex differences. In a study of the social sharing paradigm, the activity of the insula decreased in women and increased in men after transnasal oxytocin . This stThe effect of gonadal hormones on neuropathic pain has also been investigated. A study found that 17β-estradiol administration can partially rescue the poor prognosis of allodynia in female mice after CCI , which iNumerous studies confirmed that opioid analgesics have gender differences. Rodent experiments showed that male animals are more sensitive to morphine analgesia than female animals ,130. A cGonadal hormones may play an important role in the gender difference of opioid analgesia . HoweverIn recent years, social factors have been of concern in the field of pain . StudiesAs the center of information integration, the insula may play an important role in synesthesia processing. In 2006, a study reported odor and pain synesthesia in a male patient with neuropathic pain. Certain odors caused electric shock-like pain, which aggravated his neuropathic pain. Pain-related regions, including the insular cortex were activated in this process . In 2010Electrical stimulation or lesions of the insula can help us to understand how the insular lobe participates in neuropathic pain. A study of posterior insular stimulation in cats found that 50 Hz insula stimulation increased the firing rate of non-nociceptive neurons and decreased the burst firing of nociceptive neurons in the thalamus . RadiofrFrom another perspective, this synesthesia phenomenon may suggest a possibility that other sensory inputs can also modulate pain, which may become the basis and exploration direction of alternative pain treatments. Exploring how the insula processes synesthesia between pain and other sensations may also help to explore this possibility. Mindfulness is a form of physical and mental mediation, emphasizing that the trainer pays attention to and maintains awareness of interoception, such as changes in breathing. As an important processing area of interoception, the effect of mindfulness on the insula may need to be investigated. Studies found that mindfulness meditation can relieve pain . In the In this review, we described the structural and functional changes that occur in the insular cortex in the presence of neuropathic pain and after pain relief, as well as the related molecular mechanisms. We also discussed potential sex-based differences in response to neuropathic pain treatment on the basis of these molecular mechanisms. At present, the main problem is that the study of the insular lobe is still relatively limited, and there are many mysteries compared to the other brain regions. The multilevel and multidimensional information integration strategy of the insular cortex may be unique, and further research is needed to reveal its panorama.


To the Editor,The skin is one of the most commonly affected organs by the extraintestinal manifestations of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). UC may present cutaneous manifestation in 5% to 11% of patients [An 18-year-old patient presented to our dermatologic outpatient clinic for the appearance of an ulcer on the lateral side of her right ankle. Her past medical history was notable for spondylarthritis and ulcerative colitis since the age of 12, previously treated with two TNF-alfa inhibitors . At the time of our evaluation, the patient was under treatment with low doses of systemic steroids following a recent exacerbation of the intestinal disease. The cutaneous lesion had been already evaluated elsewhere a week before the presentation at our department and a cultural exam resulted completely sterile. However, the patient complained of a progressive worsening of the ulcer. On physical examination, there was the presence of a 5-cm tender ulcer exhibiting violaceous and undermined borders with a purulent base. Intense erythema was noted around the borders of the ulcers. In order to exclude the suspect of osteomyelitis, a CT scan and an MRI of the left foot and leg were performed. Both exams gave negative results concerning osteomyelitis or abscess formation but highlighted a significant involvement of the subcutaneous tissue. Also, numerous pustules were noted at the inguinal folds bilaterally and the patient referred similar episodes in the past treated as folliculitis with topical antibiotic therapy.The patient was admitted for further evaluation and during hospitalization other lesions appeared as follows: pustules were present on the left thigh, right thigh, and left gluteus. In a few hours, the pustules coalesced forming ulcers with violaceous undermined borders and a necrotic base. The patient had developed a total of four pyoderma gangrenosum-like lesions  and numerous other pustules located at the inguinal folds clinically compatible with amicrobial pustulosis of the folds.Severe tenderness of the pyoderma gangrenous-like lesions combined with a severe psychological and physical distress did not allow a skin biopsy of the pyoderma gangrenosum-like ulcers. However, the patient agreed to the skin biopsy of one of the pustules of the left inguinal fold and the histopathology report was consisted with a neutrophilic dermatosis showing perivascular and periadnexal intense mixed inflammatory infiltrate rich in neutrophils. Absence of eosinophils and no signs of microvasculitis were reported Fig. . A cutanEndovenous cyclosporine at a dose of 3 mg/kg/day aiming a serum concentration of 100–200 ng/ml and local medications with topical tacrolimus ointment 0.1% were started. Progressive improvement of both the intestinal and skin diseases was rapid: The PG-like lesions gradually improved  is a rare inflammatory neutrophilic dermatosis that typically presents as one or more painful ulcers with violaceous, undermined borders on the lower extremities. Less common presentations include tender nodules or pustules on other sites of the body. PG is the second most frequently documented cutaneous manifestation in patients with IBD after erythema nodosum . It affeAmicrobial pustulosis of the folds (AFP) is a rare, chronic, relapsing dermatosis that affects almost exclusively young women with sudden onset of follicular and non-follicular sterile pustular lesions involving the main cutaneous folds, anogenital area, and scalp as well as minor skin folds, particularly the area around the nostrils, retroauricular regions, and external auditory canals. The histWe believe that the concomitant appearance of multiple pyoderma gangrenosum-like lesions and amicrobial pustulosis of the folds suggest that these two entities are manifestations of a continuous spectrum in the context of neutrophilic dermatoses associated with IBD.While pyoderma gangrenosum is a clinically well-characterized entity, APF is a rarer disease whose clinical presentation may lead to misdiagnosis as happened in the case of our patient. In fact, the patient reported previous episodes of APF misdiagnosed as folliculitis resistant to antibiotic treatment. Pustular manifestations can be a sign of neutrophilic dermatoses as represented in this case.The simultaneous clinical presentation of pyoderma gangrenosum lesions and amicrobial pustulosis of the folds make the case of our patient a unique example of the important relationship of neutrophilic dermatoses with IBD, in this case UC. PG and APF may be linked by common pathogenetic mechanisms that led to the onset of both diseases in the context of a UC flare. PG and its syndromic forms can be considered as manifestations of a single clinic-pathological spectrum similar to that of autoinflammatory diseases, suggesting common physiopathological mechanisms.In the case of our patient, intravenous cyclosporine demonstrated to be an efficacious treatment for both the cutaneous lesions PG-like and APF and the intestinal disease.


Despite the good clinical outcomes of the conventional technique of vestibulopasty performed with a scalpel, patients frequently perceive pain and discomfort after surgery. Diode laser use in oral surgery is, instead, well tolerated as it is mini-invasive and with a very low occurrence of post-surgical complications. In addition, the lack of bleeding during surgery and the reduced/absent post-surgical edema makes diode laser surgery the most suitable for medically compromised patients. We report a case of vestibuloplasty performed by diode laser in a patient on therapy with warfarin and without drug discontinuation. It is generally accepted that the long-lasting duration of dental implants is strictly related to the quality and quantity of the keratinized gingiva . ProstheThe patient was a 75-year-old female who received four implants in the mandible for prosthetic rehabilitation by overdenture. She was in therapy with warfarin for chronic atrial fibrillation. Three months after the implant insertion, a clinical examination revealed the poor quality and quantity of keratinized gingiva around the fixtures. More precisely, it revealed the proximity of caruncula sublingualis and the absence of an inadequate deepening of both buccal and lingual vestibula of the mandible limited the prosthetic space and causing instability of the peri-implant gingiva Figures -1b. The Anticoagulant therapies are usually modified/suspended in patients needing oral surgery procedures to prevent both intra- and post-operative bleeding ,9. The gAmong all lasers with proven surgical capabilities, the diode laser is widely used for the surgical excision of proliferating lesions and photocoagulation of small and large venous malformations in the oral cavity. Although vestibuloplasty may represent an invasive procedure in medically compromised patients, especially during possible intra-operative bleeding and the following post-surgical edema of the floor of the mouth, diode laser use allows to simplify such procedure in terms of operating time, invasiveness, really reducing pain and discomfort, while at the same time achieving excellent clinical outcomes.


The identification of central sensitization (CS) is an important aspect in the management of patients with chronic musculoskeletal pain. Several methods have been developed, including clinical indicators and psychophysical measures. However, whether clinical indicators coincide with the psychophysical test of CS-related sign and symptoms is still unknown. Therefore, the present study aimed to analyze the diagnostic accuracy of the clinical indicators in identifying CS-related sign and symptoms in patients with musculoskeletal pain.One-hundred consecutive patients with musculoskeletal pain were included. Clinical indicators (index method) based on a combination of patient self-report pain characteristics and physical examination were used to identify the phenotype of patients with musculoskeletal pain and the predominance of the CS-related sign and symptoms. Conditioned pain modulation (CPM) was assessed by the Cold Pressor Test (reference standard), which is a psychophysical test used to detect impairment of CPM. Measurements of the diagnostic accuracy were performed.Twenty-seven patients presented predominance of CS-related sign and symptoms in the assessment of the clinical indicators, and 20 had impairment of CPM. Clinical indicators showed high accuracy , high specificity , high negative predictive value , and a relevant positive likelihood ratio  when compared to the Cold Pressor Test.Clinical indicators demonstrated a valuable tool for detecting the impaired CPM, which is a remarkable feature of the CS-related sign and symptoms. Clinicians are encouraged to use the clinical indicators in the management of patients with musculoskeletal pain. Musculoskeletal health conditions are a common cause of pain in the general population, and the central sensitization (CS) is linked with a number of these patients. Musculoskeletal pain is present in approximately half of the population of Europe , the UniIdentifying the pain related to CS is a clinical challenge for health professionals because there is no gold standard assessment method . BesidesThe relevant frequency of the patients with chronic musculoskeletal pain and the predominance of the CS phenotype  led reseThe lack of robust terminology to identify clinical features and neurophysiological mechanisms hamper definite decision-making in patients with chronic musculoskeletal pain. Clinical indicators have the potential to be a suitable tool for screening purposes and helpful for guiding the management of patients with different pain. Still, an investigation of the criterion validity of the clinical indicators (index method) to detect the impairment of CPM using a psychophysical test (reference standard) is needed to ensure an adequate classification of the patients. Therefore, the present study aimed to analyze the diagnostic accuracy of the clinical indicators in identifying impairment of CPM in patients with musculoskeletal pain. We hypothesized that patients with musculoskeletal pain with the clinical phenotype of the CS-related sign and symptoms would present impairment of the CPM.This diagnostic accuracy study followed the Standards for Reporting Studies of Diagnostic Accuracy (STARD) . The stuConsecutive patients with musculoskeletal pain (aged 18 years and over) of the outpatient physiotherapy of Gaffrée and Guinle University Hospital were enrolled when they sought treatment between November 2015 and May 2016. The study included patients with acute pain (pain duration less than 3 months) and chronic pain (pain duration greater than 3 months). Musculoskeletal pain was defined as pain perceived in a region of the body with muscular, ligament, bone, or joint origin , as well as in the anterior tibial region . Consequently, the within-group comparison was also statistically significant , high accuracy , high negative predictive value  and a relevant positive likelihood ratio , but low values of sensitivity  and positive predictive value  when compared to the CPT. Measurements of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the diagnosis of central sensitization are presented in Table This study investigated the diagnostic accuracy of the clinical indicators in identifying patients with musculoskeletal pain and CS-related sign and symptoms, considering the impairment of the CPM as a standard measured. Clinical indicators exhibited high values of diagnostic accuracy, specificity, the negative predictive value of the clinical diagnosis of impairment of CPM in patients with musculoskeletal pain. Besides, the positive likelihood ratio found in the current study represents a relevant increase in odds favoring a rule in patients with the impairment of the CPM. The clinical indicators demonstrated to be useful to detect impairment of CPM in patients with musculoskeletal pain, specially ruled out those patients who do not have impairment of CPM.We acknowledge strengths and limitations in the current study. The first strength is the novelty to validate the use of a practical and straightforward system of clinical identification of the phenotype of patients with CS-related sign and symptoms. The second strength was the use of a psychophysical method for impairment of CPM identification using two different anatomical sites for its classification. Ultimately, we enrolled target-positive and target-negative patients , the negative likelihood ratio was not small enough to rule out the CS-related sign and symptoms with confidence. Predictive values provide probabilities of abnormality for a particular test, but the prevalence of the abnormality in the study sample interferes with the results. In the current study, the prevalence of the CS-related sign and symptoms was 27%, corroborating a previous Brazilian study  and otheOur findings indicate that clinical indicators are an accurate tool for the identification of the CS-related sign and symptoms. Although the majority of patients with impaired CPM presented CS-related sign and symptoms, there were 20% of participants who presented divergent results. Therefore, the clinical presentation of the CS-related sign and symptoms in patients with musculoskeletal pain may be disparate from the psychophysical test, which can reveal the neurophysiological impairment. The conflicting diagnosis of the CS-related sign and symptoms in the clinical presentation and the neurophysiological test preclude adequate decision making in patients with musculoskeletal pain. Additionally, the clinical indicators were developed to identify the predominance of pain in patients with low back pain  demonstrFew studies have investigated the validity of the clinical tools to identify patients with CS-related sign and symptoms. For instance, Gervais-Hupe et al. observed sensitivity of 87.2% and specificity of 34.2% in the identification of CS using the Central Sensitization Inventory (CSI) with a cut-point of 22 in patients with knee osteoarthritis when compared to CPT . The samClinical indicators demonstrated a valuable tool for detecting the impaired CPM, which is a remarkable feature of the CS-related sign and symptoms. Clinicians are encouraged to use the clinical indicators in the management of patients with musculoskeletal pain.


Systemic lupus erythematosus (SLE) is a chronic immune-related disorder designated by a lack of tolerance to self-antigens and the over-secretion of autoantibodies against several cellular compartments. Although the exact pathophysiology of SLE has not been clarified yet, this disorder has a strong genetic component based on the results of familial aggregation and twin studies. Variation in the expression of non-coding RNAs has been shown to influence both susceptibility to SLE and the clinical course of this disorder. Several long non-coding RNAs (lncRNAs) such as GAS5, MALAT1 and NEAT1 are dysregulated in SLE patients. Moreover, genetic variants within lncRNAs such as SLEAR and linc00513 have been associated with risk of this disorder. The dysregulation of a number of lncRNAs in the peripheral blood of SLE patients has potentiated them as biomarkers for diagnosis, disease activity and therapeutic response. MicroRNAs (miRNAs) have also been shown to affect apoptosis and the function of immune cells. Taken together, there is a compelling rationale for the better understanding of the involvement of these two classes of non-coding RNAs in the pathogenesis of SLE. Clarification of the function of these transcripts has the potential to elucidate the molecular pathophysiology of SLE and provide new opportunities for the development of targeted therapies for this disorder. Systemic lupus erythematosus (SLE) is a chronic immune-related disorder described by a lack of tolerance to self-antigens and the over-secretion of autoantibodies against host DNA and other cellular elements. This disorder mostly affects females of reproductive age. SLE has a broad range of clinical manifestations that affect several organs. Approximately 50% of SLE cases will have serious and life-threatening complications such as nephritis, vasculitis, pulmonary hypertension, interstitial lung disorder and cerebral stroke . The sigLncRNAs are typically defined as transcripts longer than 200 nucleotides in length with no recognizable protein-coding potential. Approximately three decades have passed since the discovery of the first lncRNA . Based oSeveral studies have noted the dysregulation of lncRNAs in SLE patients. One study comparing transcriptomes between SLE patients and health controls identified the differential expression of 163 lncRNAs . Real-tiThe well-characterized lncRNA NEAT1 has been found to be upregulated in SLE patients . NEAT1 wA number of other previously identified lncRNAs have also been found to be dysregulated in SLE patients. For example, lnc5150 was found to be downregulated in the PBMCs of SLE patients compared with healthy individuals. Moreover, lnc3643 expression was downregulated in SLE patients with proteinuria compared with patients without this symptom. The expression of lnc7514 was decreased in patients who tested positive for anti-double-stranded DNA (anti-dsDNA) antibodies compared with those that tested negative. The expression of lnc3643 was correlated with CRP and ESR levels. Finally, the expression of lnc7514 was associated with SLE activity and ESR levels . CompariNotably, a number of studies have assessed the association between single nucleotide polymorphisms (SNPs) within lncRNAs and SLE. A recent genome-wide analysis of SLE-associated polymorphisms in lncRNA gene loci has shown an association between the rs13259960 in the SLEAR lncRNA and susceptibility to SLE. This variant is located in an intronic enhancer and changes the recruitment of STAT1 to the enhancer. Thus, the minor allele of this SNP diminishes SLEAR expression. SLEAR interacts with ILF2, hnRNP F and TAF15 to construct a complex that enhances the transcription of the anti-apoptotic genes. The role of this SNP in the regulation of apoptosis has also been verified in clinical samples . The assIn an animal model of SLE, similar dysregulation of a number of miRNAs was observed in both PBMCs and splenocytes , leadinghttps://web.archive.org/web/20110222111721/http://starbase.sysu.edu.cn/) and TargetScan v7.2 (http://www.targetscan.org/vert_72/) can be used for the prediction of miRNA targets. Non-coding RNA signatures, particularly miRNAs, are not only useful for the discrimination of SLE patients from healthy subjects, but could also potentially distinguish the presence of SLE-related complications [The highly heterogeneous nature of SLE in terms of both the underlying pathogenic processes and the manifestation of the disease course has hampered a comprehensive understanding of SLE etiology . Recent Although the association between SNPs within coding regions and the risk of SLE has been assessed in several studies , the conOverall, despite extensive research in the field of non-coding RNAs’ participation in SLE, this research avenue has not reached the level of clinical application except for a small number of studies that have verified the diagnostic/prognostic roles of these transcripts in SLE. Animal studies have raised the hope that modification of the expression of these transcripts could influence the disease course. Thus, future studies in this field may facilitate the identification of new treatment modalities for SLE.


The main goal of the study was to assess the relationship between affective temperaments and meteoropathy among women and examine meteorosensitivity as a mediator in this relationship. The issue of affective temperaments and meteoropathy has not been considered in the literature. The sample consisted of 450 Caucasian women gathered via the online recruitment platform. The participants’ ages ranged from 18 to 70 years . The Polish version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire was used to assess affective temperaments . Meteorosensitivity and meteoropathy were assessed using the Polish adaptation of the METEO-Q questionnaire. A large positive correlation was found between meteorosensitivity and meteoropathy. Medium positive correlations were found between meteorosensitivity/meteoropathy and cyclothymic and anxious temperaments. Small positive correlations were revealed between depressive and irritable temperaments and both meteorosensitivity and meteoropathy scales. No correlation was found between hyperthymic temperament and meteorosensitivity/meteoropathy. Mediation analyses indicated cyclothymic and anxious temperaments affected meteoropathy both directly and indirectly through meteorosensitivity as a mediator. The most severe meteoropathy symptoms in the studied sample were asthenia, an indefinite feeling of malaise and irritability. The results suggest affective temperaments may be related to meteoropathy symptoms in women. People are warned of the effects of changing weather on TV and through online messages every day. Every day, some people report their health deterioration or some new symptoms they associate with changes in weather—such as temperature, humidity, cloudiness or atmospheric pressure changes. This usually applies to women and older or middle-aged people, although it may also apply to children . It is eBehavioral data suggest environmental factors such as climate or weather may impact human emotional states and health conditions. For example, it was demonstrated that emotional distress decreases when exposure to the sun increases  and duriAny disorders resulting from the impact of climatic conditions can be described as meteoropathy —that is,Although the biological mechanisms of meteoropathy are unknown, in a recent study, it was suggested that superior vestibular nucleus activity may affect meteoropathy regulation in mice and probably in humans . FurtherFrom a psychological point of view, cerebral mechanisms of emotion regulation and autonomic nervous system (ANS) functioning are useful for understanding individual differences in meteorosensitivity levels and meteoropathy symptom development. Meteorological factors and other stressors may cause a challenge to the human physiological balance. When the balance is difficult to maintain, the development of somatic symptom disorder may be observed .Taking account that many meteoropathy symptoms—such as lability of mood, depression, anxiety or an indefinite feeling of uneasiness—are related to mood disorder symptoms , it is wAffective temperaments  refer to a genetically determined, stable-across-lifespan and trait-related manifestations playing a fundamental role in the predisposition to mood disorders—such as depression, anxiety and bipolar disorder , 22, 23.Molecular genetics research has provided interesting data on the strong association between central serotonergic  and dopaminergic (the hyperthymic temperament) regulation in affective temperament development . It is wAffective temperaments may share a common biological disposition with various other psychiatric or somatic symptoms, including meteoropathic disturbances. For example, the cyclothymic/irritable temperament appears to be associated with elevated stress reactivity in daily life  and somaThe main goal of this study was to assess the relationship between affective temperaments and meteoropathy among women and examine meteorosensitivity as a mediator in this relationship.We hypothesized (a) the depressive, cyclothymic, irritable and anxious temperaments are positively correlated with meteoropathy, while the hyperthymic temperament is negatively correlated with meteoropathy and (b) the meteorosensitivity dimension mediates the relationship between affective temperaments and meteoropathy.The study sample consisted of 450 white women gathered from the general population via the University of Warsaw online recruitment platform. The participants’ ages ranged from 18 to 70 years . Among the participants, 303 had received higher education, 146 had received secondary education and 1 had received primary education. Fifty-nine women lived in rural areas, 65 in small towns and 326 in large cities.This was an anonymous cross-sectional study, participation was voluntary and the participants did not receive any compensation.The data were collected via online self-report questionnaires. All participants provided informed consent to participate in the study after reading the rules of the study. Information about the purpose and procedure of the study was displayed on a computer screen. Starting the questionnaires was tantamount to agreeing to participate in the study on the given terms.The research project including aforementioned procedure and all questionnaires used was approved by the local Research Ethics Commission at the Faculty of Psychology, University of Warsaw (ref: 5-03-2019).Affective temperaments were assessed using the Polish version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) , 39, 40.Meteorosensitivity and meteoropathy were assessed using the Polish adaptation of the METEO-Q questionnaire  Polish . All iter of .1 was classified as small, .3 as medium and .5 as large per Cohen . The second analysis found a significant indirect effect of anxious temperament on meteoropathy through meteorosensitivity . The individual pathways in the mediation analysis are displayed in The results of the present research may extend the knowledge of the functional significance of affective temperaments and indicate the importance of affective temperaments for women’s meteoropathy symptoms.As expected, four affective temperaments  were positively correlated with meteoropathy among women, although the correlation coefficients were small to medium. The medium correlations between the cyclothymic and anxious temperaments and meteoropathy were revealed. These results indicate the cyclothymic and anxious temperaments may be associated with some meteoropathy symptoms similar to mood disorder symptoms. It is worth noting that the most severe symptoms of meteoropathy in the studied sample were asthenia, an indefinite feeling of malaise and irritability. Meteorosensivity was strongly correlated with meteoropathy and served as a mediator between affective temperaments and meteoropathy among the studied women. This result is not surprising because the level of sensitivity to climate or weather changes  seems to be the most important factor triggering the symptoms of meteoropathy. Therefore, one of the most important questions concerns the link between affective temperaments and meteorosensitivity and meteoropathy. The analysis of mediation shows the cyclothymic and anxious temperaments affect meteoropathy both directly and indirectly through meteorosensitivity as a mediator. The lack of sufficient data on the biological basis of both affective temperaments and meteoropathy does not allow the formulation of a clear hypothesis about the common biological mechanism of these phenomena.Nevertheless, taking account of the hypothesis on the biological basis of affective temperaments, as well as the hypothetical biological foundations of meteorosensitivity, it can be assumed that some biological associations between these variables are related to brain activity and ANS functioning. The serotonergic regulation of the cyclothymic and anxious temperaments may connect affective temperaments with the so-called somatic awareness . It is aThe probable impact of cerebral mechanisms of emotion regulation and ANS functioning on meteorosensitivity and meteoroptahy is also visible in affective temperaments traits, such as an intense experience of all emotions or rapid changes in mood and energy typical for the cyclothymic temperament  or tensiSeveral limitations of this study should be acknowledged. This research is cross-sectional in nature, making it impossible to draw any definite conclusions regarding the direction of the relationship between affective temperaments and meteorosensitivity and meteoropathy. Affective temperaments and other personality traits may play a significant role in the development of meteoropathy symptoms, but further longitudinal studies are required to corroborate this hypothesis. Another important limitation of our study is the covariability of factors treated as predictors of meteoropathy symptoms. We only used data based on self-reports, and the presence of comorbid physical and mental health disorders or substance use was not documented. Therefore, the interpretation of our results is restricted. In addition, we observed only women, thus limiting the generalizability of the results. It should be added that the study sample was not too large when considering the survey in the general population.Regardless of the methodological limitations of our study, however, our results may contribute to the understanding of how psychological factors influence weather-related changes in women's well-being. Our findings highlight the significant overlap between affective temperaments and meteoropathic symptoms among women.High levels of cyclothymic and anxious temperaments may be responsible for an increase in negative physical and mental health symptoms among women. To improve women’s well-being, meteorosensitivity and meteoropathy should be taken into account when assessing medically difficult-to-explain symptoms in women. Our results suggest that meteoropathic symptoms may be associated with moods and the dominant type of affective temperament in women. Thus, women who show mood lability and anxiety symptoms should be a focus of medical and psychological care.S1 Dataset(SAV)Click here for additional data file.


We examined the differences in physical health outcomes over a 20-year period between lesbian, gay, and bisexual (LGB) and heterosexual middle-aged and older adults. We also examined whether the associations were moderated by social support and affect. The analytical sample included 168 LGB adults and 336 propensity-matched heterosexual adults from the Midlife in the United States (MIDUS) study, ranging in age from 25 to 74 years (mean age=42.83) at baseline. Using negative binomial generalized estimating equations and mixed-effects analyses, data from three waves of MIDUS, spanning approximately 20 years from 1995 to 2014, were used to examine the associations between sexual orientation and the health outcomes . Social support and affect were added to the models to test for moderation. The results found that LGB participants reported one more chronic condition at baseline and scored significantly higher for functional limitations. However, LGB participants increased less over time for number of chronic conditions than heterosexual participants, and there were no significant differences in terms of changes in functional limitation over time. Positive affect reduced the strength of the relationship between sexual orientation and functional limitations for LGB participants. No other moderating effects were significant. The results of this study suggest that LGB individuals may become resilient to the negative health effects of minority stressors over time. Interventions should focus on improving the health of LGB individuals when they are younger and more at risk of negative health outcomes.