Suspenders are the crucial load-bearing components of long-span suspension bridges, and are sensitive to the repetitive vibrations caused by traffic load. The degradation of suspender steel wire is a typical corrosion fatigue process. Although the high-strength steel wire is protected by a coating and protection system, the suspender is still a fragile component that needs to be replaced many times in the service life of the bridge. Flexible central buckles, which may improve the wind resistance of bridges, are used as a vibration control measure in suspension bridges and also have an influence on the corrosion fatigue life of suspenders under traffic load. This study established a corrosion fatigue degradation model of high-strength steel wire based on the Forman crack development model and explored the influence of flexible central buckles on the corrosion fatigue life of suspenders under traffic flow. The fatigue life of short suspenders without buckles and those with different numbers of buckles was analyzed. The results indicate that the bending stress of short suspenders is remarkably greater than that of long suspenders, whereas the corrosion fatigue life of steel wires is lower due to the large bending stress. Bending stress is the crucial factor affecting the corrosion fatigue life of steel wires. Without flexible central buckles, short suspenders may have fatigue lives lower than the design value. The utilization of flexible central buckles can reduce the peak value and equivalent stress of bending stress, and the improved stress state of the short suspender considerably extends the corrosion fatigue life of steel wires under traffic flow. However, when the number of central buckles exceeds two, the increase in number does not improve the service life of steel wire. With the rapid development of highway transportation, long-span suspension bridges are constructed across mountains, valleys, and rivers for their good mechanical characteristics and excellent spanning performance. The construction of early large-span suspension bridges was limited by experience and technology, and structural vibration control measures were relatively lacking, leading to obvious vibration responses under external load. The longitudinal vibration displacement of structures caused by external load may lead to the fatigue of expansion joints and other ancillary components. Traffic load has been proven to be one of the main reasons causing the longitudinal vibration displacement of structures. Such vibration may cause the fatigue of expansion joints and other ancillary components ,2. SuspeCorrosion fatigue is the phenomenon of crack formation and propagation under the interaction of alternating load and a corrosive medium that leads to a reduction in fatigue resistance . ScholarFurthermore, the axial stress and bending stress fluctuations caused by relative displacements between the girder and cables easily damage the short suspenders along with fatigue degradation ,12. To rTraffic flow is an important vibration source in the suspender stress response. Suspension bridges are a flexible system and structural deformation is evident under the action of traffic flow, which varies with traffic density. Characteristics such as traffic flow parameters, vehicle type, and vehicle weight generally have random distribution ,21. The This study takes the Zhixi Yangtze River Bridge as the research object. The bridge is a single-span steel–concrete composite girder suspension bridge. The section layout is shown in As a common vibration control measure, central buckles are used to improve the vibration response of suspension bridges. These buckles are generally installed in the middle span; examples include the Runyang Yangtze River Bridge and the Sidu River Bridge, in which the rigid central buckle is installed in the middle span. Existing research indicates that the rigid central buckle can improve the structure frequency and reduce the longitudinal displacement response of the girder . In the To simulate the structural characteristics, a three-girder model of a prototype bridge was established using ANSYS 18.0. The FE model is shown in The theoretical material properties and cable force vary from the actual state of the structure; thus, the FE model was modified according to the measured material properties and cable force in construction. Then, the structure frequency was calculated by the modal analysis module of ANSYS software, and the Block Lanczos feature solver based on the Lanczos algorithm was used in modal analysis. When calculating the natural frequencies of a certain range contained in the eigenvalue spectrum of a system, the Block Lanczos method is particularly effective for extracting modes. The frequencies of the FE model were compared with measured structure frequency to validate the FE model. The research team undertook the monitoring of the structural state during the bridge’s construction. After construction, the actual vibration mode and frequency of the bridge were measured through the modal test analysis system. Besides the modal test, the vehicle loading experiment was conducted to test its deformation performance under external load. The stress of long-span bridge suspenders is caused mostly by dead load; thus, the amplitude of stress change caused by vehicle load and other live loads is relatively small and is far lower than the fatigue limit of steel wire. Therefore, the degradation process is a typical corrosion fatigue process; that is, the corrosion defects on the steel wire surface develop into initial crack damage. The entire steel wire degradation process can be divided into stages of the development of corrosion and crack propagation, as shown in 2 due to the specification of bridge designation [2. Thus, the depth of a Zn-Al alloy coating can be calculated according to its density (6.58 g/cm3) and ranges from about 29 μm to 34 μm. The corrosion of steel wire includes uniform corrosion and pitting corrosion. Uniform corrosion describes the degree of average corrosion of the steel wire surface, which directly causes the reduction in the diameter of the steel wire, and the extent of diameter reduction is assumed to stay unchanged along the steel wire length . The steignation . Accordidc is the corrosion depth of the zinc–aluminum alloy coating, ds is the corrosion depth of the steel wire, t is corrosion time, and tc is the time when the coating is totally corroded.The uniform corrosion of high-strength steel wire undergoes a two-stage corrosion process; that is, the corrosion of the coating and the corrosion of the steel wire substrate. The corrosion rate can be described as Equation (1).t is corrosion time.According to the preliminary work of the research team, the corrosion process of Galfan steel wire is measured by an accelerated corrosion test and can be simulated by parabola distribution as Equation (2) . The corIn service conditions, the corrosion rate of Galfan coating is significantly different because of the exposure environment. As is well known, field exposure tests are difficult to conduct due to the high cost of time, and it is also difficult to find exactly matched field exposure test results. Thus, the time conversion scale was determined by the field exposure test of Galfan coating by Aoki and Katayama, in which a hot-dipped Galfan-coated steel plate with a 25 μm coating was investigated ,28. AssuWhen the metal material surface has a passive or protective film, the pitting pit on the substrate surface appears after the protective layer is consumed, greatly affecting the characteristics of the steel wire. Pitting corrosion occurs randomly, accompanied by uniform corrosion . Given tThe distribution of the maximum pitting coefficient conforms ribution , which cThen, the distribution parameter of any wires with different lengths and diameters can be calculated by Equation (5):Stress concentration happens due to the shape characteristics of the corrosion pit. As the depth of the corrosion pit increases, a crack will occur when the stress intensity reaches a critical value. The transition process from pitting to cracking can be determined by two methods: (1) the growth rate of the fatigue crack exceeding that of the corrosion pit and (2) the stress intensity factor of the corrosion pit reaching the critical threshold of fatigue crack propagation. This study adopts the former method. The steel wire crack dominates when the development speed of the pitting pit depth exceeds that of the crack.a is the depth of the crack, C and m are the parameters of the Paris criterion [R is the stress ratio of alternating load.Corrosion cracks expand until failure under the stress cycle caused by an operating live load. The Forman formula is used to analyze the growth rate of a metal corrosion fatigue crack, as shown in Equation (6).riterion , Kc is ta is the crack depth, b is the diameter of the steel wire, The stress intensity factor a is the crack depth, and b is the diameter of the steel wire.tion (8) .(8)Faabi; To consider the effect of daily traffic flow on the structure comprehensively, a crack depth development model is established on the basis of daily traffic flow operation according to the traffic load investigation, as shown in Equation (9).Vehicles can be classified into different types according to axle distance, axle number, vehicle load, etc. Vehicle subsystems are commonly simplified as a car body, wheels, a shock mitigation system, and a damping system. The corresponding dynamic models are established on the basis of the hypothesis that the mass of the damper and spring components are ignored. For example, a three-axle vehicle is shown in i denotes road surface roughness.Vehicle wheels always keep contact with the deck; the bridge deformation caused by an external load leads to the vibration response of the vehicle and bridge subsystems; the dynamic response is influenced by the overall total mass matrix, damping matrix, and the overall stiffness matrix of the subsystem; and the road surface roughness is the main excitation source. Therefore, the interaction force between the vehicle and bridge system is a function of the vehicle–bridge system’s motion state and road roughness, which can be analyzed in the established vehicle–bridge analysis system . The roaThe vehicle load data monitored in a region is used to further evaluate the degradation process of suspenders under traffic load. The data were collected from the traffic load of a long-span bridge for one month by a weigh-in-motion (WIM) system. As a tensioned component, flexible central buckles cannot support the vibration response of the midspan main beam or cable as the rigid central buckles, but they can still affect the overall response of the structure by changing the fastening force. The connection system formed by the central cable and the suspenders changes the distribution of the force of the suspender near the midspan under traffic load. Traffic load is the main inducement of the bridge vibration response. To study the improvement effect of central buckles on bridge vibration, this study analyzes the response of bridges under conditions such as no central buckle and settled flexible central buckles. The detailed analysis conditions are shown in The fatigue life of suspender wires can be predicted by the corrosion fatigue theory, and the detailed prediction process is shown in E is the elasticity modulus of steel wire, and The dynamic test under truck load in Only the bending stress and axial stress of partial suspenders are shown due to layout constraints. The variation of the axial stress of short suspenders is small, whereas the length of short suspenders near the midspan is too small to release stress; the bending stress is greater than long suspenders. The influence of bending stress cannot be neglected in the analysis of suspender degradation. The settlement of flexible buckles considerably reduces the bending stress of suspenders but has minimal effect on the axial stress. The bending stress of short suspenders near suspender no. 26 (midspan) slightly decreases, whereas the long suspenders are almost unaffected. Thus, short suspenders nos. 21–26 are selected as analysis objects.The traffic load is divided into different levels according to traffic density and then used for loading to calculate the structural dynamic response under traffic conditions. The generation of pitting corrosion is a random process, and the maximum pitting depth directly affects the generation of cracks and fatigue life. In order to reflect the difference in steel wire life, the corrosion fatigue degradation of steel wire under different working conditions was simulated. A total of 150 samples for each analysis condition were sampled based on randomly generated maximum pitting coefficients, and then the transition from pitting corrosion to cracking and the crack development were calculated on the basis of the proposed predicting process. The intensity of traffic flow greatly influences the stress response of suspenders. The bending stress of short suspenders is considerably greater than that of long suspenders. The setting of flexible central buckles can effectively reduce the peak value of bending stress, but when the number of central buckles exceeds two, the increase in number does not remarkably weaken the bending stress. In addition, the buckles can share the axial stress of the suspender between inclined cables, and the weakening effect is affected by the setting position.According to numerical analysis results, the fatigue life of short suspender wires under traffic load is remarkably lower than that of the other suspenders due to large bending stress (about 27–35 years). The setting of buckles can effectively reduce the equivalent bending stress amplitude, but the equivalent axial stress amplitude does not remarkably decrease. The improved stress state of the short suspenders considerably extends the fatigue life of the steel wires under traffic flow (about 174–179 years); by contrast, the increase in the number of buckles has a minimal effect on steel wire life and extreme stress values.The influence of a flexible central buckle on suspension bridge vibration was remarkable, but the control effect on short suspenders is still unknown. This study established the corrosion fatigue degradation model of high-strength steel wire based on traffic composition and explored the influence of flexible central buckles on the corrosion fatigue life of suspenders under traffic flow. To improve the consideration of traffic flow, the WIM data were processed according to traffic density and used to analyze the suspender response under traffic flow of different densities. The fatigue life of short suspenders without buckles and with different numbers of buckles was analyzed based on monitoring traffic data. The following conclusions were drawn:The dynamic motion of the bridges is complex for diverse loads. Moreover, the fatigue behavior of short suspenders and the vibration control effect are influenced by other loads, such as wind, earthquakes, and other special conditions. The optimal design of flexible central buckles should be studied further.


Adsorption of polymeric inhibitor molecules to calcium carbonate crystal surface was investigated. Inhibiting efficiencies of phosphonic acid-based antiscalants are dependent on the amount of adsorbed material on the growing crystal surface. A strong antiscalant even at a small dose provides the necessary rate of adsorption. Comparison of two phosphonic-based antiscalants was made both in laboratory and industrial conditions. A distinguishing feature of the strong antiscalant is the presence of aminotris (metylene-diphosphonic acid) ATMP. Experimental dependencies of antiscalant adsorption rates on the antiscalant dosage values were determined. Emphasis is given to the use of nanofiltration membranes that possess lower scaling propensities. Modernization is presented to reduce operational costs due to antiscalant and nanofiltration membranes. The main conclusion is that control of scaling should be implemented together with the use of nanofiltration membranes. Application of antiscalants to control sparingly soluble salts that deposit in reverse osmosis membrane units has become one of the most important and significant issues in reverse osmosis practice ,2,3,4. APhosphonates or phosphonic acid-based antiscalants are still recognized as leading products in the reverse osmosis desalination market ,10. ThisAt the present time, interest in using reverse osmosis in drinking water supply is growing. Many new suppliers of membrane products and service chemicals are constantly appearing on the market. The tender principle of procurement leads to the situation that a low quality and inefficient product is supplied. The problem is the correct formulation of the antiscalant composition requirements. This is due to an incorrectly formulated requirement to supply a mixture of sodium salts and phosphonic acids, which is not enough to solve the problem. The initial choice of the antiscalant should be based on the results of the analysis, but later, when large amounts of antiscalants are purchased, we should analyze antiscalant samples’ nuclear magnetic resonance spectrums to ensure that the required product is used. In this article, the authors make an attempt to demonstrate a comparison of antiscalant efficiency with an account of the reduction of operational costs due to the dosing of high-quality product in the feed water.Determination of calcium carbonate crystallization rates depending on antiscalant dose and membrane type.Evaluation of antiscalant adsorption rates for different doses.Dependencies of adsorption rates on the antiscalant type and its dose.The goal of the experiments was to demonstrate the adsorption characteristics of different antiscalants and to connect adsorption ability and antiscaling efficiency of different products with the purpose of developing guidelines to reduce operational costs. The experimental program included:The laboratory test unit flow diagram is shown in The amount of calcium carbonate deposited on the membrane surface was determined by mass balance considerations as a difference between the amount of calcium in the feed water tank in the beginning of experiment and the amount of calcium carbonate at the moment of the experiment. Deposition rates of calcium carbonate were defined as the derivative of the function of the amount of deposited calcium over time.Feed water (ground water in the Moscow region) was added to feed water tank 1 and was then pumped by pump 2 to membrane module 3. Membrane modules model 1812 70 NE with nanofiltration membranes and 1812 BLN with low pressure reverse osmosis membranes were used. The Procon rotary pump was supplied by Procon Products, Smyrna, TN, USA and produced 180–200 L per hour at a pressure of 16 bar. The experiments were carried out using serial membrane elements of the 1812 standard model produced by Toray Advanced Materials Korea Inc.  with reverse osmosis membranes of the BLN model  and nanofiltration elements of the model with membranes of the 70 NE type with a selectivity of 70%. The area of the membranes in the apparatus model 1812 was 0.5 square meters.Concentrate samples were taken from tank 1. Calcium, chloride, sulphate and bicarbonate ions concentrations as well as pH and TDS values were determined in the samples. The test procedure and calculation techniques to evaluate scaling rates in the presence of antiscalants and without their addition has been discussed in a number of publications . Figure During the conducted test runs, concentration values of antiscalants (concentrations of phosphate ions) were determined a. DependAminat-K demonstrates lower scaling rates than Jurbi-Soft at different doses. The membrane type also influences scaling rate. As can be seen in Antiscalant suppliers are usually limited by general recommendations to add 1 to 10 milligrams of antiscalant per one liter of RO feed water. More detailed recommendations can be provided in accordance with the calculations that suppliers have developed for their product for a variety of application conditions. Thus, the dosing of antiscalant changes depending on supersaturation ratio reached in the membrane module depending on feed water composition and recovery values . In our Application of antiscalants provides reduction of scaling and higher values in the period between the cleanings. Figures demonstrate results of scaling rate evaluations as a function of coefficient of initial volume reduction K for the cases of different antiscalants and different dose applications. In cases when another antiscalant is used which demonstrates lower efficiency, the time period between cleanings decreases. Very often. applied cleanings are economically unreasonable. If we extend the period between cleanings, the amount of accumulated calcium carbonate grows and the efficiency of membrane cleaning decreases ,16. ThusAntiscaling efficiency of the dosed antiscalant provides reduction in scaling rates and longer operational period between cleanings. Another expense item is concentrate disposal. Concentrate produced by a reverse osmosis plant used for drinking water supply is forwarded to a sanitation sewer. For cases when ground water in Moscow region is treated by RO, the K value is usually 3–4, which means that concentrate flow value is 1/3 to 1/4 of the feed water flow. Thus, the water user water tax includes not only the costs for water treatment but costs for additional wastewater discharge. To reduce concentrate flow, an additional stage of nanofiltration membranes is used . ConcentAntiscaling efficiency of the inhibitor depends on its ability to adsorb on the surface of growing crystals. The higher adsorption rate, the better the antiscaling behavior of the inhibitor.To efficiently control scaling and to reduce operational costs of the RO unit it is recommended to tailor the membrane plant with nanofiltration membranes. The joint use of low rejection membranes and efficient antiscalant provides substantial decrease in scaling rates in membrane modules and reduces operational costs.High adsorption abilities of phosphonic-based antiscalant enables us to reduce the antiscalant dose in the feed water without compromising effectiveness of scale control and thus reduce reagent consumption and operational costs.High efficiency of phosphonic antiscalants is attributed to the content of aminotris (methylene=phosphonic acid) in the product. Application of Nuclear Magnetic Resonance method helps to identify the presence of ATMP and to avoid buying low-quality products.


Allergic rhinitis and allergic conjunctivitis are so frequently associated that the need to coin a new name to describe the simultaneous manifestations generated the term allergic rhinoconjunctivitis. The significant impact of rhinoconjunctivitis on the quality of life and the wellbeing of the patients is the reason why the medical community shows a great interest to this disease. Another aspect is the financial burden that is not negligible. The anatomical connection between the organs involved facilitates the propagation of the disease. The allergic pathophysiological mechanisms implicated in allergic rhinitis and conjunctivitis also share common features. The diagnosis of rhinoconjunctivitis is based on the concordance between the symptoms, the clinical examination, and the diagnostic tests that should reveal the existence of an allergen specific IgE in vivo or in vitro. Whilst the nasal smear for eosinophils is considered a reliable diagnostic test for allergic rhinitis, the occurrence of eosinophils in the conjunctive is not a trustworthy indicator of allergy. The therapy of allergic rhinoconjunctivitis is based on patient education, pharmacotherapy, and allergen-specific immunotherapy. The local treatment for the allergic rhinitis is primarily based on topical corticosteroids that also manage the ocular symptoms. The first line of treatment of the ocular manifestations is represented by topical antihistamines and mast-cell stabilizers or double action drugs. The patients with allergic rhinitis and other respiratory allergies are commonly affected by symptoms of ocular allergy. Allergic rhinitis and allergic conjunctivitis are often concomitant diseases showing a strong epidemiological correlation. Allergic rhinitis and allergic conjunctivitis are so frequently associated that the need to coin a new name to describe the simultaneous manifestations generated the term allergic rhinoconjunctivitis. 1].Allergic rhinitis cannot be regarded as an isolated pathology. There are other allergic disorders that are usually associated. Whenever there is an allergic inflammation of the nasal fossae, this inflammation will also involve the mucosa of the sinuses, the mucosa of the middle ear, and the conjunctiva of the eye . The financial burden of the disease is not negligible since patients with allergic rhinitis have a twofold increase in medication cost compared to non-allergic patients. In US, allergic rhinitis is the cause for 3.5 million lost workdays and 2 million lost schooldays annually .Although both conditions, allergic rhinitis, and conjunctivitis, may be regarded as trivial, their impact on the general wellbeing and the quality of life of the patients is significant [6]. In relation with the severity of the symptoms, allergic rhinitis can be divided into mild or severe. Allergic rhinitis is an inflammatory IgE mediated disease of the nasal mucosa characterized by nasal congestion, rhinorrhea, sneezing and/ or nasal itching. It can also be defined as an inflammation of the nasal mucosa occurring when a person inhales an allergen. Allergic rhinitis is categorized in connection with the temporal pattern of exposure to triggering agents, to the severity of the symptoms or the frequency of the symptoms. Traditionally, allergic rhinitis is classified into seasonal or perennial allergic rhinitis. The classification in connection with the severity and the frequency of symptoms allows a more appropriate treatment selection. This classification divides allergic rhinitis into intermittent (< 4 days/ week or < 4 weeks/ year) and persistent (> 4 days/ week or > 4 weeks/ year) , the perennial allergic conjunctivitis symptoms last all year round as other types of allergens are involved .Seasonal allergic conjunctivitis and perennial allergic conjunctivitis differ by the timeframe of the symptoms. Whilst seasonal allergic conjunctivitis symptoms are mainly manifested for a defined period of time as a response to airborne allergens  during the spring, summer or autumn [8].Vernal keratoconjunctivitis is an inflammation of the conjunctiva occurring in individuals with an atopic terrain. Conjunctival scarring and corneal complications are commonly associated with vernal keratoconjunctivitis. It is not associated with skin positive testing in 42-47% of cases proving that it is not just a IgE mediated disorder [9]. Atopic keratoconjunctivitis is a bilateral inflammation of the conjunctiva and of the eyelids connected with atopic dermatitis. A type I hypersensitivity disorder is involved in the pathophysiology of the disease [10]. Giant papillary conjunctivitis is a disease of the superior tarsal conjunctiva recognizing an immune mediated mechanism. It is believed that there is a combination between the type I and type IV hypersensitivity responses. M cells and B lymphocytes may be implicated in the pathophysiologic mechanisms of giant papillary conjunctivitis [11].Allergies represent the fifth leading group in chronic diseases, but the real prevalence of the involvement of ocular allergy is not well determined. A study on a on a substantial population published in 2010 found that up to 40% of the participants experienced ocular symptoms at least once in their lifetime [12].A study with 200 participants on subjects diagnosed with allergic rhinitis stated that approximately 90% of them also had ocular symptomatology [13]. Bousquet et al. found that approximately 88% of allergic rhinitis patients showing sensibilization to cypress pollen had concomitant allergic conjunctivitis .Evidence suggested that in seasonal allergic rhinitis, ocular symptoms are more frequent than in perennial allergic rhinitis .The original Gel and Coombs classification of allergic reactions divides the immune response in four subtypes. Type I immediate or IgE mediated; type II, cytotoxic or IgM/ IgG mediated; type III IgG/ IgM immune complex mediated; type IV delayed type hypersensitivity or T cell mediated . The sensitivity to allergens is predetermined by a genetic tendency. When exposed to a foreign inhaled protein, predisposed individuals develop a sensitivity reaction that leads to the production of specific IgE against these proteins. When the allergen is inhaled, it binds the specific IgE situated on the exterior of the mast cells generating the release of allergic mediators. The allergic immune response recognizes two stages, the early phase, and the late phase. The mediators involved in the early phase are histamine, tryptase, kinase, kinins, heparin, leukotrienes, and prostaglandins. These mediators account for the symptoms specific to allergic rhinitis: rhinorrhea, sneezing itching, nasal congestion. Mucous glands are stimulated, and the vascular permeability is increased explaining the rhinorrhea; vasodilatation explains the nasal congestion; sensory nerves are stimulated explaining the sneezing and itching. The early phase occurs in the first few minutes after the contact with the allergen. The late-phase response starts 4-8 hours after the exposure and may last for days. This phase is distinguished by the fact that it generates the recruitment of inflammatory cells such as neutrophils, eosinophils, lymphocytes, and macrophages. The symptoms of the late phase are similar to those of the early phase with the difference that the congestion and the mucus production is increased whilst the itching and the sneezing are diminished [11].Household dust and pollen were identified as most likely to induce both nasal and conjunctival symptoms producing rhinoconjunctivitis [19]. Unified airways disease is a theory that is built on the consideration that the upper and lower airways are a unified morphologic and functional unit. There are strong clinical, pathophysiological, and epidemiologic evidence that sustain this theory. The mucosa of the nose and of the bronchi present similarities and are constituted of ciliary epithelium, basement membrane, lamina propria, glands, and goblet cells, forming the so-called united airway that explains the same way of reaction. Rhinitis and asthma are chronic inflammatory diseases of the upper and lower respiratory system sharing the same allergic and non-allergic mechanisms. The treatment of rhinitis and asthma must be addressed to both inferior and superior airways in such a way to achieve a management of both diseases . The anatomical connection between the organs involved facilitates the propagation of the disease. The allergic pathophysiological mechanisms implicated in allergic rhinitis and conjunctivitis also share common features [21]. Treatment of the nasal allergy with intranasal corticosteroid can restore the patency of the nasolacrimal duct and diminish the ocular symptoms [22].The anatomical connection between the eye and the inferior meatus of the nasal fossae is realized by the nasolacrimal duct. This duct is a pathway through which the allergens and the mediators from the conjunctiva drain along with the tears in the meatus under the inferior turbinate. Nasolacrimal reflux with upward migration has been allegedly noticed by some authors but is considered unlikely to happen. The blockage of the nasolacrimal duct is expected to increase the tearing considering a simple mechanical perspective [23]. Multiple studies have established the fact that there is a nasal-ocular reflex, which explains the interrelation between the nasal and the ocular pathology. The irritation of the nasal mucosa produced by the histamine induces a response mediated by the parasympathetic nervous system. This response is experienced at the level of the conjunctiva and at the level of the opposite nasal cavity, thus generating the symptoms .Nasal allergy also induces an inflammatory response at a systemic level. This systemic upregulation might be responsible for a more rapid and intense infiltration of inflammatory cells in the conjunctiva [26]. In acute allergic conjunctivitis, mast cells are increased in number in bulbar and tarsal substantia propria. Eosinophils are present in some cases, but their absence does not eliminate the diagnosis of allergy. A study on the cytologic examination of the tarsal conjunctival scrapping of 4 groups of patients with pollen allergic conjunctivitis, atopy without conjunctivitis, acute nonallergic conjunctivitis, and normal subjects, concluded that the occurrence of eosinophils in the conjunctive is not a reliable indicator of allergy . The nasal smear for eosinophils is considered a reliable diagnostic test for allergic rhinitis with moderately high sensitivity and high specificity .The histologic exam of the nasal mucosa in allergic rhinitis has special features, presenting with nasal mucosal oedema, vasodilatation, glandular hyperplasia, and eosinophils infiltration in the lamina propria [30].The diagnosis of rhinoconjunctivitis is established by the concordance between the symptoms and the diagnostic tests. The simultaneity of the rhinitis with the ocular manifestations is of paramount importance. The symptoms encountered in the rhinoconjunctivitis are rhinorrhea, nasal obstruction, sneezing, nasal itching, tearing, swelling, ocular itching. There are special characteristics of the face of the patient with allergic conjunctivitis. The nasal crease is a horizontal crease on the nose bridge caused by the rubbing of the nose . Allergic shiners are dark circles around the eyes explained by the vasodilatation and congestion. The rhinoscopy alone cannot distinguish between the allergic and nonallergic types of rhinitis. Usually, a pale, swollen, bluish-gray mucosa in considered to be typical for allergy. The secretions typical to allergic rhinitis are watery and thin . Sometimes, in pollen allergies, differences between the results of the two tests can be observed. This phenomenon is explained by pan allergenic sensitization [32].The diagnostic tests should reveal the existence of an allergen specific IgE in vivo or in vitro. The gold standard is the skin-prick test. Detection of IgE to allergens is considered a second-line test .The therapy of allergic rhinoconjunctivitis is based on patient education, pharmacotherapy, and allergen-specific immunotherapy [34]. High local concentrations of the active principle can be attained in the nasal mucosa without systemic adverse effects. Local corticosteroids administered locally are usually well tolerated with only minor side effects. There are no major differences between the efficacy of different corticosteroid preparations. Studies have shown that their efficacity is quite similar [35]. New intranasal corticosteroids are also effective on the ocular allergic symptoms, showing efficacy through the suppression of the nasal-ocular reflex, down regulating the inflammatory cell expression, and re-establishing the patency of the nasolacrimal duct [36].Pharmacotherapy is based on local intranasal corticosteroids. Studies have shown that intranasal corticosteroids are effective not only in controlling the nasal symptoms, but also the ocular symptoms [37]. Antihistamines are also used in the therapy of rhinoconjunctivitis. The mechanism of action of antihistamines is the interference with the histamine receptors H1 in the nasal and ocular mucosae. Second generation antihistamines have a higher specificity for the H1 receptors and do not cross the blood-brain barrier and therefore they are favored, causing less sedation [38]. Ophthalmic lubricants  can be utilized to increase the humidity of the eye.Topical decongestants and corticosteroids are used to control the ocular symptoms, but the safety and optimal dosing regimen is still a matter of debate. Topical antihistamines and mast-cell stabilizers or double action drugs are the first line of treatment [39].Allergic specific immunotherapy is nowadays recognized as an effective therapy for allergic diseases. It is recommended in allergic rhinitis and allergic conjunctivitis irrespective of their association with asthma, but when there is evidence of specific IgE sensitization for a relevant inhalant allergen [Allergic rhinoconjunctivitis, the allergic inflammatory disease of the nasal mucosa and of the ocular conjunctiva, is a condition encountered with an increased frequency, related to an important decrease of the quality of life. The conjunctiva and the nasal mucosa have the same type of epithelium, this explaining why the reactivity to both allergens is similar. The allergic pathophysiological mechanisms involved in allergic rhinitis and conjunctivitis also share common features. The anatomic connection through the nasolacrimal duct, the nasal-ocular reflex, and the systemic inflammatory response, explain the relationship between the allergic rhinitis and conjunctivitis and the concomitance of the manifestations. The diagnosis of rhinoconjunctivitis is based on the concordance between the symptoms, the clinical examination, and the diagnostic tests that should reveal the existence of an allergen specific IgE in vivo or in vitro. Whilst the nasal smear for eosinophils is considered a reliable diagnostic test for allergic rhinitis, the occurrence of eosinophils in the conjunctive is not a reliable indicator of allergy. The therapy of allergic rhinoconjunctivitis is based on patient education, pharmacotherapy, and allergen-specific immunotherapy. The local treatment of allergic rhinitis is mainly based on topical corticosteroids that also control the ocular symptoms. The first line of treatment of the ocular manifestations is represented by topical antihistamines and mast-cell stabilizers or double action drugs.Conflict of Interest statementThe authors state no conflict of interest.AcknowledgementsNone.Sources of FundingNone.DisclosuresNone.


The aim of this study was to elucidate the positional relationship between the courses of the angular veins and the facial muscles, and the possible roles of the latter as alternative venous valves.The angular veins of 44 specimens of embalmed Korean adult cadavers were examined. Facial muscles were studied to establish their relationships with the angular vein, including the orbicularis oculi (OOc), depressor supercilii (DS), zygomaticus minor (Zmi), zygomaticus major (Zmj), and levator labii superioris (LLS).In the upper face of all specimens, the angular vein passed through the DS and descended to the medial palpebral ligament. In the midface, it passed between the origin of the levator labii superioris alaeque nasi (LLSAN) and the inferior OOc fibers. The vein coursed along the deep surface of the inferior margin of the OOc in all specimens. At the level of the nasal ala, the course of the angular vein was classified into three types: in type I it passed between the LLS and Zmi (38.6%), in type II it passed between the superficial and deep fibers of the Zmi (47.7%), and in type III it passed between the Zmi and Zmj (13.6%). In the lower face of all specimens, the angular or facial vein passed through the anterior lobe of the buccal fat pad.This study found that the angular vein coursed along the sites where facial muscle contractions are assumed to efficiently compress the veins, likely controlling venous flow as valves. The observations made and analysis performed in this study will improve the understanding of the physiological function of the facial muscles as alternative venous valves. The angular vein, or upper part of the facial vein, is formed by the junction of the supratrochlear and supraorbital veins at the root of the nose and becomes the facial vein near to the level of the zygomaticus major (Zmj) . As the Several textbooks indicate that the angular, facial, and ophthalmic veins lack valves –6, but sSkeletal muscle contraction is well known to be important in controlling venous blood flow in the lower limbs and in controlling tears in the lacrimal sac and gland. During standing, venous return from the lower limbs is highly dependent on muscular activity, especially calf and foot muscle contractions, which is known as the ‘muscle pump’ , 9, 10. Maes (1937)  suggesteThe angular and facial veins of 44 specimens of embalmed adult Korean cadavers  with a mean age of 72.1 years (range: 40–94 years) at the time of death were examined. The face was dissected bilaterally to expose the angular vein, facial vein, and facial muscles including the OOc, depressor supercilii (DS), zygomaticus minor (Zmi), Zmj, and levator labii superioris (LLS). The angular and facial veins were traced to observe their courses in relation to the muscles in the upper face, midface, and lower face. No history of trauma or surgical procedure was observed in any specimen.This study was approved by the Institutional Review Board of the Catholic Kwandong University (IRB no. CKU-21-01-0409). All cadavers had been legally donated to the Catholic Kwandong University College of Medicine. Donors voluntarily consented to the dissection and preservation of their body for education and research purposes. The donor’s family agreed with the contents and procedures according to the will of the donors. None of the donors was from a vulnerable population and all donors or next of kin provided written informed consent that was freely given. The study was performed in accordance with the Declaration of Helsinki .The course of the angular vein in the face was recorded in relation to the facial muscles and surrounding structures. In the upper face, it passed through the DS and descended to the medial palpebral ligament in all specimens . In the This study has revealed that the courses of the angular vein in the face appear to have close positional relationships with the facial muscles including the OOc, DS, and Zmi. As the angular vein courses deep to the margins of the facial muscles or passes between them, it can be compressed during muscle contractions, affecting venous flow and the spread of inflammation, especially under conditions of blood pooling such as supine, prone, or upside-down positions or during blood backflow during a Valsalva maneuver or exercise.In the upper face, the angular vein passed through the DS fibers that depress the eyebrow, acting as a muscle of the glabellar complex. When the DS contracts, its fibers can compress the angular vein. Thus, blood flow from the angular to the superior ophthalmic vein and then to the cavernous sinus can be controlled, reducing the likelihood of inflammation spreading to the cavernous sinuses.In the midface of all specimens, most parts of the angular vein coursed along the inferior margin of the OOc. The orbital portion of the OOc induces considerable lower eyelid elevation during eye closure . The OOcThe angular vein passed between the superficial and deep fibers of the Zmi, between the LLS and Zmi, or between the Zmi and Zmj. In the first two courses, it can be compressed more due to the narrow space between the muscle fibers. The Zmi also acts with the LLSAN and LLS as one of the muscles causing elevation during several facial expressions and mouth movements . ContracThis study has revealed that the angular vein passes through the buccal fat pad in the lower face, where the mouth and mandible move frequently. Nishihara et al. (1995)  indicateThe experimental study of Cotofana et al. (2020)  found thThe limitation of this study is that this observation based on the cadaveric dissection was unable to assess the blood flow of the angular vein. As a further study, venous blood flow and diameter of the angular vein or facial vein can be investigated via ultrasound imaging at the sites where the vein was located along with the muscles during several facial expressions.This study found that the angular vein coursed along the sites where facial muscle contractions are assumed to efficiently compress the veins, likely controlling venous flow as valves. The observations made and analysis performed in this study will improve the understanding of the physiological function of facial muscles as alternative venous valves.


People with schizophrenia experience higher levels of stigma compared with other diseases. The analysis of social media content is a tool of great importance to understand the public opinion toward a particular topic.The aim of this study is to analyse the content of social media on schizophrenia and the most prevalent sentiments towards this disorder.Tweets were retrieved using Twitter’s Application Programming Interface and the keyword “schizophrenia”. Parameters were set to allow the retrieval of recent and popular tweets on the topic and no restrictions were made in terms of geolocation. Analysis of 8 basic emotions  was conducted automatically using a lexicon-based approach and the NRC Word-Emotion Association Lexicon.Tweets on schizophrenia were heterogeneous. The most prevalent sentiments on the topic were mainly negative, namely anger, fear, sadness and disgust. Qualitative analyses of the most retweeted posts added insight into the nature of the public dialogue on schizophrenia.Analyses of social media content can add value to the research on stigma toward psychiatric disorders. This tool is of growing importance in many fields and further research in mental health can help the development of public health strategies in order to decrease the stigma towards psychiatric disorders.


An Infection Control Estimate (ICE) Tool was developed based on a previously published concept of applying military planning techniques to Infection Prevention and Control (IPC) management strategies in the acute healthcare setting.Initial testing of the outbreak management tool was undertaken in a large acute hospital in the North-West of England during a localised outbreak of COVID-19. The tool, developed using Microsoft Excel, was completed by trained IPC practitioners in real-time to log outbreak details, assign and manage meeting actions and to generate surveillance data.The ICE tool was utilised across five outbreak control meetings to identify and allocate tasks to members of the outbreak control team and to monitor progress. Within the meetings, the tool was used primarily by the trained IPC Specialist Nurses who were guided by and entered data into the relevant sections. Feedback indicated that the tool was easy to use and useful as the sole repository of outbreak information and data. Suggested improvements following the testing period were made and additional functionality was added.Utilisation of the ICE tool has the potential to improve our understanding of the efficacy of currently employed outbreak management interventions and provides a cognitive support and targeted education for teams responsible for the management of outbreaks. It is hoped that by guiding teams through an outbreak with prompts and guidance, as well as facilitating collection and presentation of surveillance data, outbreaks will be resolved sooner and risks to patients will be reduced. The COVID-19 pandemic generated numerous challenges to healthcare services and has in many cases hastened a transition towards digital ways of working. These challenges highlighted several key issues related to the management of outbreaks of infectious diseases. Firstly, an appreciation of the importance of robust and timely datasets to support decision making has been realised during contact tracing and epidemiological modelling efforts . SecondlThe most recent Centre for Workforce Intelligence review of the IPC (Infection Prevention and Control) workforce highlighted those approaches to infection control service delivery, including outbreak management, are varied and there is little consistency in the training, practice or philosophies underlying IPC services in the UK (United Kingdom) . In respThis article will discuss the first proactive application of this novel outbreak management tool during an outbreak of COVID-19 in a large acute hospital in the North-West of England.aide memoir as a cognitive support to ensure that key elements of planning are not missed. In the context of the ICE, a prototype digital tool was developed using Microsoft Excel and contains data entry fields and guiding questions. The tool supports the development, monitoring, and allows retrospective analysis of the efficacy of outbreak management efforts by facilitating data extraction with potential to be used as metric for outbreak management efficacy and quality. In a military context, the CE questions are typically used alongside an In 2021, the ICE protype tool was used for the first time during a live outbreak at a hospital in Northwest England. The outbreak concerned SARS-COV-2 and lasted 44 days, during which time 36 patients were infected. The outbreak was contained to a single ward.The ICE tool prototype was used to document information related to the outbreak and answers the seven questions which constitute the estimate . For exan = 41) of outbreak interventions were either elimination or administrative interventions with the minority of interventions (n = 12) representing substitution, engineering controls or personal protective equipment-based interventions.Throughout the outbreak, the ICE prototype tool was used to record key data related to the outbreak in addition to being used to help plan and evaluate control measures. A retrospective analysis of the ICE tool used during the outbreak identified 53 interventions employed. These were automatically analysed by the tool and categorised into the relevant hierarchy of control (HOC) categories . This anThe tool was utilised across five outbreak control meetings to identify and allocate tasks to members of the outbreak control team. The tool also indicates when these tasks were completed. Within the meetings the ICE tool was used primarily by the trained infection control specialist nurses who were guided by and entered data into the tool. It was reported that the tool was found to be easy to use and captured all necessary data, although new data collection fields were suggested during the outbreak including detailed recording of issues and negative impacts of management interventions.The ICE prototype is the first digital tool which centralises key data related to the management of outbreaks in the context of inpatient hospital settings. The data captured within the ICE tool has the potential to improve our understanding of the efficacy of currently employed outbreak management interventions, the economic impacts of outbreaks and provides a cognitive support and targeted educational tool for teams responsible for the management of outbreaks. By ensuring that all aspects of the ICE seven questions are addressed within the tool, teams can be more confident that all key elements of the outbreak control process have been considered and all potential interventions have been implemented and evaluated. Future development of the tool will include the addition of greater communication functionality in addition to automated analysis of data captured within the tool to help better understand the efficacy of interventions and facilitate rapid and effective dissemination, and archiving, of the outbreak management plans to relevant clinical staff and leaders. Whilst this initial pilot testing of the tool during an outbreak has demonstrated the basic usability of the tool, wider robust testing is required to evaluate the value and potential impact of the ICE on outbreak management processes.


Multifamily interventions have shown to reduce the risk of relapse of psychotic symptoms in first episodes of psychosis (FEPs) but are not frequently implemented in specific treatment programs. We have develop a pilot study for the implementation of the interfamily therapy in FEPs within a Mental Health Centre in the Community of Madrid.The aims were to examine: relapses , duration of re-hospitalizations and voluntary versus involuntary re-hospitalizations during participation in MFG compared with the previous year.21 subjects participated in a MFG during 12 months, 11 participants with a diagnosis of psychosis and 10 family members. Interfamily therapy works as a new model of interactive psychoeducation among families where they share their own experiences and look for comprehension and solutions all together.Our clinical experience in an interfamily therapy intervention over 12 months has led us to identify a high degree of participation and acceptance by users and their families, and we have observed a lower relapse rate, with fewer of psychiatric admissions and of shorter duration among patients during the year of participation in the MFG compared to the year before treatment.MFG has been well accepted by both patients and their families, with a high degree of participation.The results observed in our experience of MFG treatment are consistent with the findings of previous studies that support the reduction of the relapse rate, the number of hospitalizations and their duration when family interventions are incorporated into treatment in recent-onset psychosis, especially in a multi-family group format.No significant relationships.


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. There appears to be a duplicated image, with some possible signs of alteration, between the first two panels of Figure 4E.


The antenatal diagnosis of an unruptured true aneurysm of the uterine artery is extremely rare and has never been reported, whereas pseudoaneurysms associated with previous trauma or cesarean section have been reported several times. True aneurysms occur when the artery or vessel weakens and bulges, sometimes forming a blood-filled sac. Nearly all cases of pelvic true aneurysms involved ovarian arteries which ruptured during the peripartum period. The case presented here is unique in terms of being an unruptured true aneurysm of the uterine artery with a first diagnosis during pregnancy at 32 weeks of gestation and the spontaneous development of thrombosis in the aneurysm in late pregnancy, documented at 37 weeks of gestation. The diagnosis of a true aneurysm of the uterine artery was based on, (1) a demonstration of the cystic mass located in proximity to the lower segment of the uterus with ultrasound characteristics of arterial flow in the mass, and (2) the occurrence in a woman who had no history of trauma or surgery in the pelvis. The finding during cesarean section confirmed the prenatal sonographic finding. The pregnancy ended with successful outcomes.


The authors discuss functional characterization of Mousterian tools on the basis of their use-wear and residue analysis of five lithic tools from Mezmaiskaya cave and Saradj-Chuko grotto in the North Caucasus. The results represent the first comprehensive use-wear and residue analysis carried out on Mousterian stone artefacts in the Caucasus. This study unequivocally confirms the use of bitumen for hafting stone tools in two different Middle Paleolithic cultural contexts defined in the Caucasus, Eastern Micoquian and Zagros Mousterian. Homo . Our understanding of the use of composite tools by the Middle Palaeolithic (MP) Neanderthals in Eurasia relies on evidence of hafting and adhesives4. Most ideas on the development of Palaeolithic composite tool technologies are based on microscopic use-wear, including diagnostic impact fractures (DIFs) and other traces of use15, and diagnostic characteristics of hafting traces10 , and the morphology of tools . However, the exact hafting significance of use-wear traces and morphological features is not always clear16, and this evidence alone are not an exhausted indication of the presence of hafting technology. Also, some studies indicate that the interpretative potential of some impact fractures proposed as having diagnostic value for the identification of projectiles is still unclear18.The development of composite technology using adhesive materials is often seen as a hallmark of cognitive sophistication that played an important role in the social and technological development of the genus 20, two lumps of birch tar that were probably attached to a bifacial knife from Königsaue (Germany)21, and nine tools and flakes with pine resin, and one scraper with pine resin and beeswax from Fossellone and Sant’Agostino caves 22 in Europe, as well as 14 tools and flakes with bitumen from the sites of Umm El Tlel and Hummal (Syria) in the Levant26. These studies document that adhesive technology was used in both Europe and south-west Asia by varied Neandertal populations and the MP production of adhesives was complex. Neandertals mixed pine resin with beeswax22 and bitumen with quartz and gypsum24, and distilled tar from birch bark20.The lithic residue analysis provides direct information that the lithic artefacts were hafted, as well as allows precise identifying the adhesive materials involved in the manufacture of these composite tools. The currently known unambiguous evidence of the securely dated, and chemically and spectrometrically identified MP hafting adhesives includes three flakes with birch tar from Campitello Quarry  and Zandmotor (Netherlands)20], the level of adhesive technology applied for manufacturing composite tools among different Neanderthal groups is problematic given the lack of relevant data from the majority of MP regional contexts. This state of research demonstrates the need for detailed modern studies about the role of adhesives in hafting and the level of hafting technology in various MP regions.Despite the MP adhesive evidence is being increasingly documented in Europe and Asia  established the methodological framework for examination of archaeological residues in our study. The absorption bands corresponding to specific bitumen bands were defined after75. Band assignments for Raman peaks were made based on36.The good preservation of the analyzed lithic artefacts allowed us to identify use-wear traces and residues on all archaeological samples. Various articles focused on the characterization and identification of common materials found in various applications


The direct and indirect striatal pathways form a cornerstone of the circuits of the basal ganglia. Dopamine has opponent affects on the function of these pathways due to the segregation of the D1- and D2-dopamine receptors in the spiny projection neurons giving rise to the direct and indirect pathways. An historical perspective is provided on the discovery of dopamine receptor segregation leading to models of how the direct and indirect affect motor behavior. Prevailing models of basal ganglia function are based on two main pathways originating from separate populations of the spiny projection neurons (SPNs) in the striatum that either directly or indirectly connect to output circuits that affect motor behavior. These direct and indirect striatal pathways were proposed to differentially promote and suppress actions in hyperkinetic and hypokinetic clinical disorders . The disFrom a historical perspective research on the basal ganglia pioneered neuroanatomical approaches for understanding the organization of brain circuits underlying brain disorders. Seminal work by Arvid Carlsson and Oleh Hornykiewicz in the late 1950s-early 1960s established that Parkinson’s disease results from the degeneration of dopamine systems in the basal ganglia. This led to the development of a precursor of dopamine, L-DOPA as an effective treatment that reversed the bradykinesia symptomatic of the disease .in situ hybridization histochemistry (ISHH) to localize genes expressed in neurons, retrograde and anterograde axonal tracing methods and intracellular labeling of the axonal projections of individual striatal neurons. These techniques were used to describe the direct and indirect striatal pathways that form the conceptual backbone of the functional organization of the basal ganglia  and indirect (iSPN) output pathways was provided by a technique developed by in situ hybridization labeling of mRNA transcripts (ISHH) added a powerful technique that advanced characterization of striatal neurons giving rise to the direct and indirect pathways. Using this approach, ISHH localization of neurons expressing substance P or enkephalin mRNAs combined with fluorescent retrograde axonal tracers confirmed that dSPNs express substance P mRNA whereas iSPNs express enkephalin mRNA  that activate transcription factors to regulate gene expression of IEGs and others to modify neuronal plasticity and physiology . In addi2+/calmodulin signaling systems that activate mitogen-activated protein kinase kinase (MEK) responsible for phosphorylation of ERK1/2   . In thesas-GRF1) , 2008, sas-GRF1) , 2021. Bas-GRF1) . Cocaineas-GRF1) . These sas-GRF1) . Direct + influx  or Drd1 + influx  and indi+ influx . ActivatA major area of research is to determine the functional cellular effects of dopamine mediated activation of signal transduction pathways . An examChanges in dendritic morphology and physiologic properties of dSPNs and iSPNs were studied following striatal dopamine denervation with treatments with L-DOPA that produced dyskinesias by Surmeier, Cenci and their colleagues . DopaminOriginal concepts of the role of the basal ganglia in the generation of voluntary movements focused on activity from the cerebral cortex through the direct striatal pathway inhibiting the output of the GPi and SNr to disinhibit thalamic and brainstem circuits that generate movements . The ide2+ influx as a measure of neuronal activity  of the GPe to the output nuclei of the basal ganglia are diagrammed in To further study the opponent effects of activity in the direct and indirect pathway during normal behavior Chan and his colleagues  used an These studies expand the conceptual model that the direct and indirect pathways function to promote selected actions and suppress alternatives . Rather The effect of the direct and indirect basal ganglia pathways on behavior is determined by the organization of cortical input to the striatum. In the prevailing model of the organization of the basal ganglia, parallel circuits originate from functionally defined cortical regions that project through striatal projections to the output targets in the thalamus, which project back to the cortex . SubregiActivity in the direct and indirect pathways is initiated by excitatory inputs from the cortex and thalamus. A critical question is whether individual cortical and thalamic neurons that provide inputs selectively target dSPNs and iSPNs or provide inputs to both. To address this question modified rabies virus was used to label cortical neurons that provide inputs to dSPNs or iSPNs that express Cre . ResultsA core feature of the basal ganglia are the opponent functions of parallel pathways that process cortical input through the direct and indirect pathways to affect action selection. These pathways originate from dSPNs and iSPNs in the striatum. Opponent effects of dopamine on these neurons is a consequence of its stimulation of dSPNs through the Drd1 receptor and inhibition of iSPNs through the Drd2 receptor . DopaminThe author confirms being the sole contributor of this work and has approved it for publication.


Different hip pathologies can cause geometric variation of the acetabulum and femoral head. These variations have been considered as an underlying mechanism that affects the tribology of the natural hip joint and changes the stress distribution on the articular surface, potentially leading to joint degradation. To improve understanding of the damage mechanisms and abnormal mechanics of the hip joint, a reliable in-vitro methodology that represents the in vivo mechanical environment is needed where the position of the joint, the congruency of the bones and the loading and motion conditions are clinically relevant and can be modified in a controlled environment. An in vitro simulation methodology was developed and used to assess the effect of loading on a natural hip joint. Porcine hips were dissected and mounted in a single station hip simulator and tested under different loading scenarios. The loading and motion cycle consisted of a simplified gait cycle and three peak axial loading conditions were assessed . Joints were lubricated with Ringer’s solution and tests were conducted for 4 hours. Photographs were taken and compared to characterise cartilage surface and labral tissue pre, during and post simulation. The results showed no evidence of damage to samples tested under normal loading conditions, whereas the samples tested under overload and overload plus conditions exhibited different severities of tears and detachment of the labrum at the antero-superior region. The location and severity of damage was consistent for samples tested under the same conditions; supporting the use of this methodology to investigate further effects of altered loading and motion on natural tissue. Hip osteoarthritis causes debilitating pain and loss of function and affects over 300 million people worldwide . The cauDespite evidence from clinical and in silico studies , 5 demonWhile the in vitro assessment of the mechanical environment on the natural hip is limited, total hip replacements have been widely studied using experimental hip simulators. These in vitro simulators are able to apply clinically relevant loading and motion cycles to hip replacements in a lubricant that mimics synovial fluid. The effects of parameters such as the material the hip replacement is made from, its diameter, the relative position of the components; as well as load and motion cycles applied have been assessed –8.In order to develop further experimental simulation of the natural hip, a reliable in-vitro methodology where the position of the sample, the congruency of the bones and the demand of load and motion are clinically relevant is needed. Such a methodology can develop our understanding of abnormal mechanics of the joint and possible damage mechanisms. The aim of this study was to develop and validate a methodology for experimental simulations of the natural hip joints using an electro-mechanical simulator and use the developed methodology to demonstrate the effects of altering the mechanical environment (increased loading). We hypothesised that the developed method would enable us to differentiate between loading environments thought observation of damage to the natural hip cartilage and labrum.Porcine hip joints were selected for use because of their availability and lack of variation compared to cadaveric human tissue. The materials section describes the preparation of the porcine samples for testing; and the methods section describes the experimental simulator that was used, the loading and motion protocols adopted for testing and the post-test analysis.Twelve right hind legs from 6-month-old pigs were obtained within 24-48hrs of slaughter. Animals were slaughtered at the local abattoir  and taken from the food chain.All soft tissue surrounding the hip joint was removed by dissection. Prior to disarticulating the joint , the neutral position between the femur and acetabulum was assumed to be when the centre of the transverse acetabular ligament (TAL) aligned with the inferior apex of the growth plate in the head in the direction of the lesser trochanter. At this position, the capsule also exhibited a neutral visible tension, indicating the resting position of the joint . The resOn the pelvic side, bone was resected so approximately 5 mm of peri-acetabular bone around the acetabulum was maintained and the laburm remained intact. The posterior periacetabular bone was resected parallel to the acetabular rim in order to avoid any interference with the acetabular fossae soft tissue that could have led to cement flowing into the articular surface .The diameters of the head and acetabulum were recorded. Head diameters were measured using circular templates at the centre of the head in a parallel plane to the epiphyseal line . PositioThe method of sample mounting was developed to ensure three main objectives: 1) the COR of the hip was coincident with the COR of the simulator, 2) the neutral position of the joint and the relative position between bones were anatomically correct, and 3) there was no impingement of the fixtures within the RoM used in the experimental testing. An overview of the fixtures used are shown in In order to mount the acetabulae in an anatomically correct position, the acetabulum was placed with the TAL positioned towards the raised portion of the acetabular cup holder . The aceThe (inverted) femur was placed in anatomical alignment in the acetabulum and fixed using a custom potting fixture . The samAn electro-mechanical Single Station Hip Simulator (SSHS); Simsol Simulation Solutions Ltd., Stockport, UK, was used to perform the in-vitro experimental simulations . The SSHThe porcine hip joints, mounted in holders as previously described Figs  and 6, wFour porcine hips were tested under conditions representative of normal peak load (NOR). The load and motion profile selected was based on the ISO standard for total hip replacement (THR) wear testing (ISO 14242). The axial load was scaled due to the reduced load expected in a quadruped and the average mass of the animals –15. The The effects of mechanical loading on the porcine hip was considered in further testing with increased loading, as follows: the overload condition  used the load profile described above with an increase in peak load to 1,130 N corresponding to an approximate increase of 25% of the NOR loading and the overload plus  condition with peak load of 1340 N which represented an approximate increase of 50%. In all loading profiles  the loadThe experimental simulator applied simultaneous motions representative of human gait to the femoral head, as follows: ± 20 Flexion-Extension (FE), 8.8 to -4.8 degrees of Abduction-Adduction (AA) and 2 to -10 degrees of Internal-External Rotation (IER), . The medPhotogrammetry was used to characterise and catalogue the tissue condition and record the location/extent of damage labrum and/or articular cartilage pre, during , and post simulation  for all the samples. Multiple photographs were taken (Canon 750D DSLR with wide lens EF-S 28-70mm F3.5–5.6 and EF 100mm f 2.8 USM Macro) of both articular surfaces and the labrum following a standard protocol to ensure photos were captured in a consistent manner .Output simulator data was monitored to ensure the input and output profiles were consistent. Input profiles, data generated in terms of input and output profiles and photographs for each test are openly available through the University of Leeds data repository .A methodology was developed that enabled the in vitro simulation of porcine hip with a standard walking cycle. It was possible to set up the simulation to ensure the COR of the femoral head and acetabular were consistently coincident with the COR of the simulator. During method development two technical failures (results excluded) occurred, one whereby there was cement ingress between the articular surfaces, and another where the femoral neck fractured.Loading conditions were derived for “normal walking” (NOR) and two “overload” (OL and OL+) scenarios. Following testing under the normal (NOR) conditions (n = 4) for 14400 cycles there was no detectable damage to the articular surface or acetabular labrum. Representative images of the samples pre- and post- test are shown in Following testing under the overload (OL) conditions, damage to the cartilage labral junction was observed. Tears and detachment of the labrum at the antero-superior region were observed (n = 4) at the end of the simulation (14400 cycles). However, no damage was detected when samples were reviewed at 7,200 cycles.In the case of all of the Overload Plus (OL+) scenarios, similar damage to that in the Overload (OL) conditions were observed, however, this was also larger in size and occurred earlier in the testing , some signs of tearing were also observed after 2 hours of testing. Overload Plus conditions also showed cartilage bruising on the articular surface of the acetabulum. The type of damage to the articular surface and labral junction during the experiments at different time points are shown in Figs Different hip pathologies can lead to a change in bony shape cause abnormal loading. This change in loading effects the tribology of the hip joint, and the increased stress distribution on the articular surface leads to mechanical failure and accelerates degeneration. Hip joint simulators have been widely used to perform tribology studies to evaluate the wear of total hip replacement components under different conditions, such as increased loading and RoM from daily activities and also the effects of changing the position of the THR components –8. Such In the methodology presented in this study, a protocol was developed whereby the natural hip could be accurately and reproducibly set up in a simulator, accounting for sample variations. The bespoke fixtures ensured the COR was reliably set in all tests and was coincident with the COR of the simulator. The required disarticulation and the removal of the greater trochanter in sample preparation had the potential to compromise the stability of the joint, however, the method provided accurate positioning of the sample into the simulator and a very quick and reliable method for the macro evaluation of the articular surface (due to the disarticulation). The hip remained stable throughout testing.Surface assessment and photogrammetry provided an accurate and fast approach to evaluate the cartilage and labral surfaces during and after simulation. The wide lens photographs provided a clear visualisation of the overall condition of the samples every time they were taken to identify the location of possible tissue damage. The macro photographs allowed observations of the detailed condition of a particular region of interest and to identify the type and severity of damage occurred. Photogrammetry took place in the same location as the experiment, allowing quick and minimal manipulation of the sample.Following testing under the normal load condition, the porcine hip samples showed no evidence of damage. This provides evidence that this is an appropriate methodology and loading regime for in vitro studies on porcine hips and provides a benchmark to compare the effect of different loading conditions. The overload and overload plus conditions did cause increasing amounts of damage. This was is in agreement with previous in vitro testing of natural cartilage samples, that have demonstrated increasing damage with increasing load , 18, 19.The developed methodology has some limitations. The removal of the great trochanter in the porcine samples was necessary to allow an appropriate RoM and avoid impingement between bones. This could affect the stability of the joint . The joint was disarticulated, which was required to fix the sample and to evaluate the articular surfaces through the test. It would have been ideal to maintain the capsule and teres ligament to preserve their function during the motion. The number of samples per loading condition was limited (n = 4), however development of the alignment and mounting methodologies used more samples (n = 10), therefore we were able to refine this process and reduce variability from joint position and ensure the damage observed was consequence of the loading and not of malpositioning of the sample. Finally, testing used cadaveric tissue and consideration to the differences this makes compared to living tissue should be considered. This may include the lubrication mechanism of the cartilage and recovery of the tissue from loading, and the contributions from viable cells in the cartilage. The altered lubrication will increase, stresses in the articular surfaces and we postulate damage occurs faster than in living tissue.Future work will further assess the effects of altered loading and motion of the natural hip, the effects of misaligning the joint will also be assessed and can be used to gain insight into surgical processes used to reshape the hip (for example in the case of femoroacetabular impingement). The developed methods will be translated to human cadaveric tissue.


Many genetic disorders are a result of single or multiple genome abnormalities. A possible approach to circumvent genetic disorders is to use gene editing agents to correct these mistakes, but a major challenge remains in the mode of delivery of gene editing agents to different regions of the body. Banskota et al. present the use of engineered DNA-free virus-like particles (eVLPs) to deliver base editors to different organs in a mice model for improved outcomes, highlighting the potential of eVLPS to deliver base editors and as an efficient delivery mechanism, leveraging the advantages of viral and nonviral delivery methods. Abnormalities in the genome can bring about various genetic disorders. A possible approach for the treatment of genetic disorders is by correcting these harmful mutations. Gene editing agents have provided an avenue to manipulate genomic DNA in living organisms with great precision. This approach provides the possibility to edit the genome to alleviate the origin of many genetic diseases. A major challenge to carry out this repair is the delivery mechanism of the editing agents to different regions of the human body. Current approaches commonly use adeno-associated viruses (AAVs) to deliver the DNA that encodes for specific base editors. However, concerns surrounding the use of virus delivery systems includes prolonged expression causing off-site mutations and possible oncogenesis from viral vector integration.1 recently described the design of virus like particles (VLPs), which is in essence a hollow protein shell of the virus devoid of any viral genetic material, allowing for the delivery of ribonucleoproteins (RNPs) in place of DNA, to reduce the chance of off-target editing thanks to the shorter lifetime of RNPs in cells. Banskota et al. utilized these engineered VLPs (eVLPs) to deliver therapeutic RNPs, including base editors and Cas9 nuclease. The new design allows eVLPs to package 16-fold more base editor RNP compared to earlier versions of VLPs. The authors successfully applied the eVLPs for delivery to different sites in the animal host. The system was able to reduce serum Pcsk9 levels in the liver and restore visual function in a mouse model of genetic blindness.Banskota et al.The published system signifies the possibility of utilizing eVLPs to deliver gene editing therapies to circumvent genetic disorders at different locations in the human body with a minimized risk of off-target mutations. More importantly, the system can also be applied for the in vivo delivery of other therapeutic proteins and RNPs. The nature of the production of eVLPs means there is a possibility that cellular proteins and RNAs from the originating cell could be packaged alongside the eVLPs. Therefore, in depth protein profile analysis of the eVLPs with an optimized production system would have to be established to reduce immunogenicity issues. The pharmacokinetics of the eVLPs need to be completed to determine the half-life of eVLPS, the cargoes and dosing requirements, and although there are still some aspects of eVLPs that have yet to be clarified, the current developments bode well for the potential of eVLPs for the treatment of genetic disorders in the future.


Here, we report a case of an 80-year-old man with a history of hypertension and recurrent episodes of syncope and chest pain. First, he underwent a coronarography with revascularization of the right coronary artery and stent placement. The exploration of the left main coronary artery (LMCA) was not performed because of catheterization difficulties. A coroscanner was performed for suspicion of an anomalous of the left coronary artery. The coroscanner showed an uncommon case of left main coronary artery (LMCA) arising from the right sinus of Valsalva. The proximal part of the interventricular artery has an intra-arterial course between the aorta and the pulmonary outflow tract, with narrowing of this artery at this level (2.2 mm in diameter). Left main coronary artery (LMCA) or left anterior descending coronary artery (LAD) arising from the right sinus of Valsalva or right coronary artery (RCA) is referred to as an anomalous aortic origin of a coronary artery (AAOCA). The subsequent course is mostly between the aorta and the pulmonary artery on its way to the left ventricle. Different theories have been postulated as a cause of sudden death in these patients. The most accepted theory is the higher incidence of occlusion of the osmium secondary to a more slit-like orifice and occlusion during physical activity due to compression between the major arteries.


Recurrent Unipolar and Bipolar affective disorders are considered paradigms of biological entities in psychiatry. However recent theories have underlined the role that environment plays in the genesis of these disorders in interaction with genetic diatheses.This study examined the relationship between stressful life events (SLE) and recurrent major depressive disorders.Three groups of 50 subjects were assessed: Patients with recurrent major depressive disorder with melancholic features; patients with borderline personality disorder; and healthy controls. Interviews for DSM-V Disorders were used for diagnosis. Beck Depression Inventory, The Israel Psychiatric Research Interview Life Event Scale and the Coddington Events Schedule were used to measure life events and depression and were confirmed with an interview.The proportions of loss-related events in childhood and in the year preceding the first episode was higher in the depressed group than in the control groups during the same time period. Proportions of SLE, uncontrolled and independent events were also more common in the depressed patients in the year preceding the first episode.The study’s conclusion is that SLE plays an important role in the onset of depressive disorders. There are specific kinds of SLE that occur in childhood and in the year preceding the first episode. SLE has a less significant role in the maintenance of this illness.No significant relationships.


Workplace social capital is the relational network, created by respectful interactions among members of a workforce, can contribute to the formation of a wholesome psychological work environment in an organization. Nurses' workplace social capital is a derivative of the workplace social capital, formed because of the complex interactions among the nursing and between the other healthcare professionals. Transformational leadership is a style of leadership that addresses the emotional wellbeing of its workforce and inspires shared group ethics, norms, and goals. The philosophy of transformational leadership is grounded on the premise of workforce as human beings with specific needs. Transformational leadership has been confirmed as a strong predictor of nurses' workplace social capital. Meanwhile, it is of an academic and/or healthcare industry operational value to scholarly assess and discern the theoretical influence of transformational leadership on nurses' workplace social capital. In this paper, we have attempted to explore the associations between transformational leadership and nurses' workplace social capital from a theoretical perspective. We have discussed the importance of each sub-dimension of transformational leadership  in building up the social capital relational network. Finally, we have proposed a graphic framework of our analysis to facilitate understanding of the associations between the transformational leadership and nurses' workplace social capital, in formation of a healthy work environment which is the foundation for efficiency and productivity of the workforce. Nursing professionals account as the largest segment of the healthcare workforce. Public ranks nursing as the most trusted profession . The terWorkplace social capital is an intangible but a formidable source that can improve effectivity and productivity of a workforce . Nurses'Transformational leadership can strongly influence the development of nurses' workplace social capital . This stThe concept of social capital first was used by Hanifan in 1916 to depict the relationships and interactions within a community . The semThe pivotal role of social capital at workplace  has been pronounced and palpated across the globe due to intra and inter connectivity within and among the workforce and the increase in demand for productivity . The colThe concept of “social capital” was introduced into the field of academic nursing in the mid-1990s . E.A. Rerelational network configured by respectful interactions among nursing professionals and between the other healthcare professionals. These interactions are characterized by the norms of trust, reciprocity, shared understanding, and social cohesion”  suggests the direction of the relationships in the workplace social capital network. The current presentation of nurses' social capital displays Type as a standalone pillar. We would like to propose to reposition of placing the three segments  of Type under the pillar of Component, within the classification of structural social capital. We rest our proposition based on the rational that these three segments  describe the structural directions of workplace social capital relational network. We have allocated the rest of this manuscript to logically assert our proposal.The importance of leadership in human interactions and relationships cannot be denied. Since the dawn of civilization various models and philosophies of leadership have been proposed, implemented, and practiced. The most current model, transformational leadership, introduced in the late 1970 s, has been put into practice by many organizations and has become one of the predominant relationally focused leadership styles –10. Tran1) Modeling the Way; (2) Inspiring a Shared Vision; (3) Challenging the Process; (4) Enabling Others to Act and (5) Encouraging the Heart , which are the two main attributes of nurses' workplace social capital . The cognitive social capital  embedded in this strong and healthy vertical social capital network will be incubated and flourished.The nurse manager is the closest leader to the other nursing professionals at any ward. If we make the analogy of clinic workplace as a ship sailing on the open sea, the nurse manager with transformational leadership style would be the sagacious navigator. She/he sets up the shared standards of excellence (shared understanding) in the ward and clarifies uncertainties so that the other nursing professionals can reach to a higher level of professional destinations. Nurse managers with transformational leadership style can be trusted and create mutual trust among nursing professionals that can lead to the affirmation of a strong vertical relational network  is also an important attribute of cognitive social capital. In some healthcare settings, nurse professionals are still considered as the subordinate group and are prone to workplace discrimination  can be strengthened with increased enthusiasm for a shared future blueprint  is raised simultaneously along with these positive interactions.The second component of transformational leadership is bilities ; shared mination . Nursinglueprint ; team cochallenge the process always seek out opportunities for changing their own status quo and that of others  in addressing and overcoming the workplace challenges and obstacles. Challenges in the delivery of healthcare services require cooperation across disciplines in finding practical and plausible answers to the problems on hand  and generating valuable cognitive assets e.g., trust, reciprocity, cohesion .The nursing workforce has been faced with tremendous challenges as the results of the rapid changes and responsibilities that have been introduced into the profession since the turn of the 21st century . Transfof others . Transfo on hand . This conabling Others to Act is another important resource for building the workplace social capital. Group accomplishment cannot be fulfilled by the leaders alone. Transformational nurse leaders always strive to build good relationships with people at workplace  through tolerance and consideration. The transformational nurse manager seeks opportunities for staff's personal and professional growth and performance extraordinaire  between the transformational nurse managers and the other nursing professionals  because the authenticity of their leaders gets exuded through sincere actions.The practice of Eorkplace . Nursingorkplace . Transfordinaire , 39. SucEncouraging the Heart of the transformational nurse managers contributes to the formation of nurses' workplace social capital. They acknowledge and celebrate group and individual victories in inspiring the team spirit   and stru) in the team; furthermore, the transformational nurse manager can apply the accomplishments of the nursing professionals in developing and/or strengthening professional interactions and camaraderie between the nursing professionals and the other healthcare providers .Finally, the practice of m spirit . They heIn summary, transformational leaders can develop and establish intimate and yet professionally appropriate emotional ties, high-level trust, team interaction and shared visions with the members of their teams , 40. TheNursing professionals are the backbone of the healthcare industry and a strong force to improve the cost effectiveness of the delivery of healthcare services. Nursing professionals communicate and cooperate with each other and the other healthcare professionals within the complex social capital network. A well-woven nurses' workplace social capital network is the tenet for a healthy work environment and ensures the efficiency and effectiveness of delivery of healthcare services. Measures to enhance nurses' workplace social capital should be put on the agenda by institutional administrations to assert flourishing of nurses' workplace social capital; furthermore, other workplace measures should be addressed through legislations and implementation of healthcare and public policies to ascertain preparedness of the healthcare industry for future challenges. Empirical research has shown that the relational-oriented transformational leadership provides an effective way to strengthening the workplace social capital for nursing professionals.In our paper, we have proposed possible mechanisms of transformational leadership on nurses' workplace social capital from a theoretical perspective. The detailed analysis triangulating with the empirical results should formulate constructive suggestions for nurse administrators and policymakers when striving to develop workplace social capital. Additionally, our analysis should shed light on clues for researchers in other scientific fields when attempting to explore the interactions between leadership and social capital in their domains. The main strength of our study is its proposed theoretical perspective mechanism of influence of the transformation leadership on nurses' workplace social capital. Our perspective analysis has its limitation. Our theoretical work was designed to address the theoretical deficiency of the interaction between transformational leadership and nurses' workplace social capital. In consequence, the influence of variables such as task structure, or leader position power, or impact of situation type were not evaluated. Meanwhile, our work is a prelude for future theories for each specific nursing context, pillared by transformational leadership and nurses' workplace social capital. Future research should evaluate influence of elements such as leader and subordinates' relationship and/or task structure and their interaction with these two concepts. Despite its limitation, our work shed light on constructive suggestions for nurse administrators and policymakers when striving to develop workplace social capital for nursing professionals.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.J-MX and AS conceptualized the framework of the manuscript. All authors have contributed to the development and approval of the manuscript.This work was supported by Public Welfare Technology Application Research Project of Lishui Science & Technology Bureau, China (Project No. 2022GYX65).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Neurological and neuropsychiatric disorders pose a significant burden on human health and society throughout the world. In the past 30 years, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially  and adiponectin . Ge and Dai report about the effects of 3-week treadmill exercise on the electrophysiological and channel properties of serotonergic neurons located in the dorsal raphe nucleus. In the paper by Liśkiewicz et al. it is analyzed whether stimulation of autophagy is one of the mediators of ketogenic diet induced neuroprotection in the hippocampus.Two articles report about further molecules that are involved in regulating physical exercise stimulated adult hippocampal neurogenesis, namely the cyclin-dependent kinase inhibitor p16Ink4a (This Research Topic aimed to bring about new findings on the cellular and molecular processes that impact brain function in health and disease. The data presented here mainly focus on the beneficial role of ketonic diet and physical exercise on brain function, including the effects on neuronal circuitries and neuronal plasticity. Taken together, the articles support the view that the balance between nutrition and exercise is of paramount importance for cognitive health and the maintenance of brain structures.The author confirms being the sole contributor of this work and has approved it for publication.


Prevention of the First Episode of Psychosis: What Have we Reached by 2021? The first episode of psychosis is usually preceded by a prodromal period or stage of psychosis, where early signs of symptoms indicating onset of first episode psychosis (FEP) occur. In the last twenty years, enormous progress was made in the tretment of FEP and subsequently schizophrenia, as the focus of treatment of FEP shifted to this prodromal period with the aim of preventing the first episode of psychosis in people at risk.Treatment for the prodromal stage of psychosis is provided within specialized early intervention services, which are somtimes part of the services for the treatment of FEP. Early intervention services, which have been gradually developed in many countries worldwide, usually incorporate multimodal treatment approaches . However, there are still many differences in the treatment of prodromes across early intervention services, even within one country, leaving open the questions on what kind or combinations of treatments really work in the prevention of FEP. The methods of studies in the scientific psychiatric literature do not allow easy translation of scientific data to clinical practice. In the presentation, an up-to-date overview of the available treatments offered witin early intervention services for prevention of FEP is given.No significant relationships.